Randomized controlled trials

By Dr. Jayeeta Choudhury,PhD, FICN , Dr. Uliyar V Mani
Corresponding Author Dr. Jayeeta Choudhury,PhD, FICN
Director, Centre of Nutrition Research, Gujarat , J-902, Indraprasth Tower, Drive inroad, Ahmedabad - India Ahbd - 380052, Gujarat
Submitting Author Dr. Jayeeta Choudhury, PhD, FICN, FACN (USA)
Other Authors Dr. Uliyar V Mani
Dept Of Foods & Nutrition & WHO Collaborating Centre, The M.S University Baroda, - India Baroda


Surgical Gastrointestinal (G.I) Patients, Severely Malnourished (Sm) Glutamine (Gln), Routine Hospital EN Diet (EnR), Soy-rich EN (EnS), Routine Hospital EN with Substrate Enriched Enteral Glutamine (GEnR), Glutamine-Soy Rich EN (GEnS), Length of Stay (LOS)

Choudhury,PhD, FICN J, Mani UV. Effect Of Soy and Glutamine as Substrate for Enteral Nutrition Compared to Standard Hospital Regimen Among Surgical Patients - A randomized , Single Blind Controlled Trial.. WebmedCentral NUTRITION 2012;3(7):WMC003511
doi: 10.9754/journal.wmc.2012.003511

This is an open-access article distributed under the terms of the Creative Commons Attribution License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Submitted on: 02 Jul 2012 05:37:48 AM GMT
Published on: 03 Jul 2012 04:43:48 PM GMT


Surgical stress affects whole body protein kinetics, demands increased need for optimal nutrition. Data suggests glutamine (Gln) as metabolic fuel for the G.I tract cells and its supplementation has important effects in catabolic surgical patients. Routinely practiced conventional Hospital Enteral Nutrition (EN) regimes for such subjects fail to provide both.
Objective: To examine the impact of postoperative polymeric kitchen – based Soy enriched EN regimen and substrate enriched with Enteral Gln versus Routine Hospital EN /enriched with Gln   on overall nutritional status in surgical G.I subjects.

Methods: Seventy-one surgical G.I subjects were randomised to receive either one of the supplemented polymeric kitchen-based enteral diets - [Soy rich EN (EnS), Routine Hospital EN with (EnR)], substrate enriched with enteral Gln (0.35 g kg-1day-1) [Gln-soy rich EN (GEnS), Routine Hospital EN enriched with Gln (GEnR)]. Impact on overall nutritional status [Total protein (TP), Albumin (Alb), Weight gain / loss, Length of stay (LOS)] for the groups and ‘severely malnourished subjects’(Sm) were studied. 

Results: Sm were 57.15% of the total (NRI score). EnS had a significant weight gain (3.98 %), shorter LOS (16.5 days), higher percentage had an upward trend in TP [52.4%], Alb [66.7%] levels as compared to control (EnR). Better results were elucidated by the patients of GEnS with significant weight gain (3.87%), shorter stay (14.5days), higher percentage with significant improvement in TP 93.3%; Alb 86.7% as compared to GEnRs. Sm subjects of both the study groups had an upward trend of Alb with a significant weight gain [EnS (+2.42 Kg), GEnS (+3.24 Kg)] to a significant weight loss noted in Sm controls [EnR -3.77 Kg; GEnR -1.15 Kg].  Sm-subcategory of EnR’s to EnS had longer pre-operative stay (3.9 vs 3.0 days) and total LOS (19.9 vs. 16.7 days). Sm-subcategory of GEnS to GEnR reflected shorter LOS (15.8 vs. 18.0 days). Thus, GEnS and Sm had an overall improvement in nutritional status with significant shorter stay.

Conclusion: Early post-operative substrate-enriched EN can improve postoperative outcomes beyond standard routinely practiced EN even in Sm subjects.


Surgery is a high catabolic state with greatly increased rate of protein turnover and further increased nutritional and calories demands. Post-surgical complications burden the health care extending hospital stay. Delivery of balanced diet including an adequate amount of protein or suitable amino acid preparation with required substrates might greatly facilitate an anabolic response to life threatening disease including minor/major surgical procedures. Post-operative enteral nutrition (EN) has been shown to be both effective, well tolerated and is also associated with specific benefits such as reduced incidence of post-operative infectious complications. Several observations support the concept that glutamine (Gln), a conditionally essential amino acid, is also an important dietary nutrient during surgical catabolic states acting as metabolic fuel for the cells of the G.I tract. Even most of the research and its connection to G.I diseases are in conjunction with the use of TPN and gln-supplemented parenteral nutrition appears to maintain nitrogen balance and intracellular glutamine and in skeletal muscle better than parenteral nutrition not supplemented with glutamine. [1] As nutrition support is an expensive so efforts must be made to utilise it appropriately, effectively and efficiently. Routinely kitchen based EN for hospitalised surgical patients are generally low in good quality protein and gln. Moreover, due to added cost, commercial EN products are not in common use for low socioeconomic group and use of gln rich supplemented EN is impossible in such cases. Therefore, the ideal way would be to feed protein rich diet and additionally supplementing this ‘magical amino acid’. Aim was to develop a low cost polymeric kitchen based EN formula and to study the therapeutic efficacy of postoperative Soy rich EN and Gln - soy rich EN versus routinely EN practiced in hospital on overall nutritional status of surgical G.I patients and especially in ‘severely malnourished’ category.

Patients and Methods

1. Seventy-one surgical G.I patients constituted the candidates of this study with approval by ethics committee based on predetermined protocol. Eligibility included surgical G.I subjects with no history of IDDM or cardiac disease (class III & IV), normal renal function, and non-pregnant women. Here we made use of most commonly available natural plant protein and gln rich source i.e. Soy. This prospective randomised study comprised of two parts and compares: Firstly, the impact of polymeric kitchen – based protein rich soy supplemented EN (EnS, n = 21) with Routine Hospital EN (control: EnR, n = 21). Secondly, the impact of gln-soy enriched EN (GEnS, n = 15) and Routine Hospital EN diet (control: GEnR, n = 20) with substrate-enriched gln.
2. Nutritional Status: On admission, anthropometry, biochemical, dietary assessments were done and body mass index (BMI)  [2] was calculated. Serum albumin level was recorded and nutritional risk index (NRI) [3] was calculated especially to study the nutritional status of the severely malnourished subcategory subjects of the respective study groups
3. EN Composition and Diet Administration: The respective groups received either one of the isocaloric (1000 Kcal L-1) EN diets with nutrient composition of 21% protein, 30% fat and 58% carbohydrate [routine hospital diet (EnR), polymeric kitchen- based soy rich EN (EnS)]. Gln-soy rich EN (GEnS) and control-glutamine (GEnR) study groups received additionally an average of 0.35 g kg-1day-1 gln to above mentioned kitchen-based EN. The concerned clinician instigated the mode and route of EN support based on clinical assessment of the intestinal function. Patients were kept either on TPN followed by EN or directly into EN. Supplementation of the feeding formulas was done during postoperative EN stage with calorie needs estimated using Harris-Benedict equation. [4]   The initial rate of delivery was 50ml hrly-1 full strength EN feed as a continuous infusion with 6 hours rest at night thereby gradually increasing step wise to a full intake (24 - 48 hours) according to patient’s tolerance. During this build-up period, tubes were aspirated every 2 hours and nutrition intakes, feeding related problems were monitored daily. Nutrition support was continued on an average for 10 d or until the subject was able to consume as oral diet.
4. Outcome Measures and Statistical Analysis: Impact of diets on hemogram, biochemical, body weight, LOS was studied to describe the therapeutic efficacy and overall health economic benefit of specialised nutrition for both control and study group (EnR, GEnR, EnS, GEnS). All parametric data were expressed as means (SD). Comparison between groups was made using students – t test or Mann Whitney’s U test for qualitative data. [5] A p value of 0.05 or less was taken to signify a statistically significant difference


Seventy-one patients [controls (EnR, GEnR) and study (EnS, GEnS) groups] age range (17-65 years) fulfilled study entry criteria and consent was obtained. Overall the upper G.I diseases composed of 66.2 %, lower G.I diseases 12.7 % and 21.1 % as miscellaneous group {Table-1}. At admission, 44.0 % of the total subjects (n = 71) on admission had weight loss more than 10 % of UBW and serum albumin levels for all the groups were at risk level {Table-2}. NRI score rated 57.15 % of the total enrolled patients as ‘severely malnourished’(Sm). The average pre-operative intakes of major nutrients were significantly low for EnR and EnS study groups thereby resulting in deficit energy intake as compared to requirements. GEnR and GEnS study groups had adequate pre-operative energy intake but significantly low protein intake as compared to their requirements (p < 0.05). Although during postoperative stage supplementation was done either through transnasal or enterostomy tubes but calorie and protein intake was noted significantly low in EnR group whereas, EnS group had better intake as compared to their respective requirement {Table-3}. Further, Sm-subcategory of EnR group recorded considerably low intake of major nutrients during postoperative stage thereby resulting in lower energy as compared to their requirements whereas energy and protein intake of Sm-subcategory of EnS group was adequate {Table-3a}. Similarly, comparison inadequacies of post-operative intake among groups further reflected a significant improvement for GEnR and GEnS study groups {Table 3}. The Sm-subcategory of respective study groups had adequate intake of calories but a significantly low protein intake (p < 0.05) compared to their requirements {Table-3a}. However, the reasons for decreased intake may be due to feeding related complications. ETF commonly causes G.I symptoms in feed related complications. Nausea and diarrhoea occurs up to 10-20 % [6] and 30 % of patients in medical or surgical wards or more than 60 % of the patients on ICU. [7] Abdominal bloating and cramps from delayed gastric emptying are also common. [8] Our study also detects reductions in the incidences of nausea (16%; 6.6%), diarrhoea (46%; 26.6%), vomiting (45%) and abdominal discomfort in EnS and GEnS study groups as compared to EnR’s and GEnR’s respectively. Impacts of diets on improvement in protein status, weight gain/loss, LOS was not equally effective. Protein status in EnS group improved (TP: 6.60 gdl-1 vs. 6.18 gdl-1, Alb: 3.44 vs. 3.10 gdl-1) whereas, the levels dropped in EnR post-operatively group (TP: 4.84 gdl-1 vs. 4.99 gdl-1, Alb: 2.73 gdl-1 vs. 2.77 gdl-1) as compared to admission. On the other hand, GEnR study group had a negligible improvement in total protein (5.01 gdl-1 vs. 5.00 gdl-1) whereas, GEnS study group an improvement in both the levels (TP: 6.20 vs. 5.53 gdl-1 Alb: 3.20 gdl-1vs 2.85gdl-1) {Table-4}. Moreover, comparison between groups (EnR, GEnR, EnS, GEnS) showed a significant improvement (p < 0.05) in both the levels in EnS and GEnS {Table- 4}. Further, Sm (Severely malnourished) subcategory of the EnR and GEnR study groups had a downward trend for hemoglobin and total protein levels whereas an upward trend in albumin level was noticed after EN stage {Table-4a}. During discharge a significant weight gain was observed in EnS (+2.04Kg) and GEnS (+2.20 Kg) groups {Table-5}and even in Sm-subcategory of EnS (+2.42 Kg) and GEnS (+3.24 Kg) study groups (p< 0.05) whereas a significant weight loss was found in Sm subjects of EnR ( -3.77 Kg) and GEnR (-1.15 Kg) study groups (p< 0.001) {Table-7}. With respect to LOS( Length of stay), overall though EnR’s had a longer duration of pre-operative stay (EnR: 4.5 days vs. EnS: 3.0 days) but total hospital stay was also noted significantly longer as compared to EnS study group (p < 0.05) (EnR: 12.2 days EnS: 11.4 days) {Table-6}. Even, Sm-subcategory (Severely malnourished) of EnR’s had both longer (3.9 vs. 3.0 days) pre-operative stay and total (19.9 vs. 16.7 days) hospital stay as compared to EnS study group {Table-7}. Similar picture was noted in GEnR group as compared to GEnS group [Pre-op stay:  2.9 vs. 1.7 days; Total hospital stay: 18.7 vs. 14.5 days] {Table-6}. Comparison between Sm-subcategory of GEnS and GEnR groups reflected shorter total stay in GEnS  as compared to the GEnR study group (15.8 vs. 18.0 days) {Table-7}even with similar days of pre-operative stay (2.1 vs. 2.4 days). To summarise, overall GEnS study group and even Sm subcategory had significant shorter stay compared to GEnR and EnS study groups respectively (p < 0.05).


The present randomised study describes the efficacy of good quality protein and gln- supplemented EN as specialised nutrition support in a surgical patient population with an increased risk of nutritional depletion risk due to underlying disease condition. Recent report describes that subjects undergoing elective major procedures if malnourished, are adequately fed for at 7-10days [9] or even with IED for 5-7days pre-operatively appears to improve clinical outcome. [10] We could not provide the subjects with pre-operative supplemented nutrition support because of their unwillingness for longer hospital stay as it might add total cost of treatment. Comparison inadequacies of post-operative intake among groups reflected that post-operative energy and protein intakes were significantly higher in EnS, GEnS groups as compared to their controls (p<0.05) [Mann-Whitney U test]. Interesting feature here is that though total protein and albumin levels for both the groups were below normal at admission, post-operative supplementation resulted a significant improvement in EnS group and also in Sm patients as compared to EnR group (p < 0.05). Though post-operative weight loss (a mean of 1.8 kg in patients receiving intravenous fluids) is acceptable because short-term under nutrition (10 -12 days) do not complicate convalescence after major surgery. [11] Here EnR group had 8.66% weight loss whereas weight gain of 3.98% was noted in EnS study group. Moreover, Sm subcategory of EnS study group had a weight gain of 5.33 % compared to 7.26 % weight loss of the same in control (data not shown). Independent of immunomodulation specialised nutrition support, [12] LOS after surgery was significantly (p < 0.05) reduced by 5.9 days in EnS group as compared to longer stay for EnR’s (22.4 days). An overall improvement in the nutritional status concludes the beneficial effect of good biological protein (Soy). This study also draws attention to the positive benefits of gln-soy rich EN (GEnS) and Routine Hospital EN (GEnR). Gln, a conditionally essential amino acid reported to modulate protein metabolism in intestine. [13] Marked improvements in the levels were noted in GEnS study group. Further, a negligible improvement in total protein was observed in GEnR’s. Even, Sm patients of both the study groups had an upward trend of albumin. Thus, supplementation of gln might have acted as an added benefit in improving protein status. These matches to some extend with the study reported by Lin et. al., where their results with gln supplementation showed a tendency to have cumulative nitrogen balance on the post-operative days in patients with low APACHE II scores. [14] Moreover, overall GEnS study group and especially Sm subcategory patients had a significant weight gain and shorter stay as compared to GEnR’s (p < 0.05) thereby matching with the study reported by Powel et. al., with gln supplementation. [15]  Interestingly, on overall comparison between groups (EnR, GEnR, EnS, GEnS) with and without glutamine enriched EN, an improvement in the protein status was noted even in GEnR patients as compared to EnR’s [(TP: 66.7 % vs. 43.0 %) (Alb: 73.3 % vs. 52.4 %)]. Though a higher percentage of patients in EnS study group had an upward trend in both the levels but still a much better results were elucidated by GEnS group [(TP: 93.33 % vs. 52.4 %) (Alb: 86.7 % vs 66.7 %)] compared to EnS group. Overall, Sm subcategory of all the groups had an upward trend in albumin level. EnS and GEnS study groups elucidated a significant weight gain with shorter LOS (16.5days, EnS), (14.5days, GEnS) vs (22.4days, EnR) vs (GEnR 18.7days). Even weight loss was observed less in gln-control group as compared to EnR’s. Such findings parallel recent studies that describe economic advantage of a significantly decreased LOS with the provision of specialised nutrition support. [16] Our analysis suggests ‘substrate enriched with Gln appears to provide therapeutic advantage’. 


This study with small number of surgical G.I patients demonstrated potential benefits of low cost soy-supplemented EN and gln-supplemented soy rich EN over conventional regimens. Elevation in total protein, albumin levels, increment in weight, shorter LOS may be explained in the light of impact of good quality protein source with natural glutamine source of soybean. [17] Moreover,shorter hospital stay markedly diminished hospital costs. This economic implication is surely an added advantage for the lower socioeconomic populations. Although encouraging results were obtained there remains a need for further trials with individual G.I diseases.


1. Barton RG. Immunoenhancing enteral formulas: Are they beneficial in critically ill patients? Nutr  Clin Pract 1997;12:51-62.
2. ACCM’s Guidelines for exercise (2000) Testing and prescription 6TH edition, American College of Sports medicine.
3. Schneider SA and Hebuterne X . Use of nutritional scores predict clinical outcomes in chronic diseases. Nutrition Reviews  2000; 58(1): 31 – 38.
4. Harris JA and Benedict FG. In : Biometric studies of basal metabolism in man, 1919. Pub.no. 270, Carnegic Institute of Washington, Washington DC .
5. Gupta SP.In: Statistical Methods.  New Delhi  , Sultan chand and sons; 1993. A3.31–A-11.13.
6. Jones BJM, Lees R, Andrews T Frost P, Silk D B A. Comparision of elemental and polymeric enteral diet in patients with normal G.I function. Gut 1983; 24:78 - 84 (Abstract).
7. Benya R, Layden TJ, Morbarchans S. Diarrhoea associated with tube feeding: the importance of using objective criteria, J Clin Gastroenterol 1991;  13:167 - 72 (Medline).
8. Duncan H D, Silk DB. Problems of treatment - enteral nutrition. In Nightingale J ed. Intestinal failure. London; Greenwich Medical Media Ltd:2001. 477 - 76
9. Veterans Affairs total Parenteral Nutrition Cooperative Study group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med 1991; 325: 525 - 2.
10. Woodcock NP, Zeiglar D, Palmer D, Buckley P, Mitchell J, Macfic J. Enteral vs Parenteral Nutrition – A Pragmatic study. Nutrition 2001; 17:1 - 12.
11. Sandstorm R, Drott A, Hyltander A, Arfirdsson B, Schersten T, Wickstron I et al.The effect of post-operative intravenous feeding (TPN) on outcome following major surgery evaluated in a randomised study. Am Surg 1993;217:185 -5.
12. Weitzelberg DL, Saito H, Plank LD, Jamieson GG, JagannathP, Hwang TL, Mijares JM, Bihari D.  Postsurgical infections are reduced with specialised nutrition support World J Surg 2006; 30:1 - 13.
13. Clinical trials, 2005.Available from : http:// www clinical trials.gov.com
14. Lin  Mt, Kung SP, Yeh SL, Lin C, Lin TH, Chen KH, Liaw KY, Lee PH, Chang KJ, ChenWJ. Effect of glutamine supplemented total parenteral nutrition on nitrogen economy  depends on severity of diseases in surgical patients . Clin Nutr 2002; 21(3);213 - 8.
15. Powell TJ, Jamieson CP, Bettany GE, Obeid O, Fawett HV, Archer C, Murphy Dl. A double blind randomised controlled trial of glutamine supplementation in parenteral nutrition  JPEN 1999; 45(1):6 - 7.
16. Wyncoll D, Beale R.  Immunologically enhanced enteral nutrition , current status. Curr Opin Crit care  2001; 7:28 - 32
17. Subbulakshmi G. Soy in human health, Quaterly Medical Review 2004; 55(1) 3 - 12.

Source(s) of Funding

Own Funding of Dr. Jayeeta Choudhury

Competing Interests



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5 reviews posted so far

Responded by Dr. Jayeeta Choudhury, PhD, FICN, FACN (USA) on 13 Jul 2012 05:19:59 AM GMT

Effect of Soy and Glutamine...
Posted by Dr. Ram B Singh on 04 Jul 2012 11:51:05 AM GMT

I wish to Thank You for Reviewing the article and sparing your valuable time.... View more
Responded by Dr. Jayeeta Choudhury, PhD, FICN, FACN (USA) on 04 Jul 2012 05:03:28 PM GMT

Thanks for ur valuable time.... View more
Responded by Dr. Jayeeta Choudhury, PhD, FICN, FACN (USA) on 04 Jul 2012 05:00:48 PM GMT

I wish to thank u for Reviewing my article.... View more
Responded by Dr. Jayeeta Choudhury, PhD, FICN, FACN (USA) on 04 Jul 2012 04:59:33 PM GMT

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