Mécanismes d’action potentiels de la glutamine chez le patient agressé

Several controlled studies and recent meta-analysis indicate that glutamine supplementation has beneficial effects on clinical outcome of critically ill and surgical patients. These effects could be explained in part by the role of glutamine as the preferential substrate of rapidly dividing cells but also by its influence on inflammatory and immune response, on oxidative stress, on heat shock protein expression and on glucose metabolism. Indeed, glutamine supports gut barrier function by stimulating gut protein synthesis and epithelial cell proliferation and by limiting apoptosis. In addition, glutamine enhances intestinal and systemic immune response and antioxidant defences such as glutathione pool. Glutamine also induces the expression of heat shock proteins that play a key role in cellular protection. In contrast, glutamine decreases intestinal and systemic inflammatory response by decreasing pro-inflammatory cytokine production but also by increasing anti-inflammatory cytokine production. This effect of glutamine on inflammatory response may be mainly related to its capacity to reduce NF-κB activity. More recently, some data indicate that glutamine may reduce insulin resistance and thus the risk of infectious complications.     

Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants

BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk and may be conditionally essential in premature infants. However, glutamine is not provided by standard intravenous amino acid solutions. OBJECTIVE: We assessed the effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants receiving parenteral nutrition (PN). DESIGN: A total of 141 infants with birth weights of 401-1000 g were randomly assigned to receive a standard intravenous amino acid solution that did not contain glutamine or an isonitrogenous amino acid solution with 20% of the total amino acids as glutamine. Blood samples were obtained just before initiation of study PN and again after the infants had received study PN (mean intake: 2.3 +/- 1.0 g amino acids x kg(-1) x d(-1)) for approximately 10 d. RESULTS: Infants randomly assigned to receive glutamine had mean plasma glutamine concentrations that increased significantly and were approximately 30% higher than those in the control group in response to PN (425 +/- 182 and 332 +/- 148 micromol/L for the glutamine and control groups, respectively). There was no significant difference between the 2 groups in the relative change in plasma glutamate concentration between the baseline and PN samples. In both groups, there were significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples; the decrease in tyrosine was greater in the group that received glutamine. CONCLUSIONS: In extremely low-birth-weight infants, parenteral glutamine supplementation can increase plasma glutamine concentrations without apparent biochemical risk. Currently available amino acid solutions are likely to be suboptimal in their supply of phenylalanine, tyrosine, or both for these infants.     

Nonnutritive effects of glutamine

Glutamine is the most abundant free amino acid of the human body. Besides its role as a constituent of proteins and its importance in amino acid transamination, glutamine has regulatory capacity in immune and cell modulation. Glutamine deprivation reduces proliferation of lymphocytes, influences expression of surface activation markers on lymphocytes and monocytes, affects the production of cytokines, and stimulates apoptosis. Moreover, glutamine administration seems to have a positive effect on glucose metabolism in the state of insulin resistance. Glutamine influences a variety of different molecular pathways. Glutamine stimulates the formation of heat shock protein 70 in monocytes by enhancing the stability of mRNA, influences the redox potential of the cell by enhancing the formation of glutathione, induces cellular anabolic effects by increasing the cell volume, activates mitogen-activated protein kinases, and interacts with particular aminoacyl-transfer RNA synthetases in specific glutamine-sensing metabolism. Glutamine is applied under clinical conditions as an oral, parenteral, or enteral supplement either as the single amino acid or in the form of glutamine-containing dipeptides for preventing mucositis/stomatitis and for preventing glutamine-deficiency in critically ill patients. Because of the high turnover rate of glutamine, even high amounts of glutamine up to a daily administration of 30 g can be given without any important side effects.     

Effects of parenteral nutrition supplemented with alanyl-glutamine on nutrition status in rats

BACKGROUND: Glutamine, a nonessential amino acid, has received increasing attention because it becomes essential during stress and catabolic conditions. Many investigations have shown that during severe stress, the consumption of glutamine exceeds glutamine synthesis, resulting in depletion of glutamine stores. The aim of this study was to evaluate the effects of supplementing parenteral diets with a glutamine-containing dipeptide, L-alanyl-L-glutamine, on rat nutrition status. METHODS: Male Wistar rats were used. Animals (n = 36) were centrally catheterized and randomly assigned to 1 of the following groups based on method of parenteral nutrition (PN): control group with oral nutrition and IV infusion of a saline solution; standard parenteral nutrition (SPN) group; or alanyl-glutamine-supplemented PN (ALA-GLN PN) group (20 g/L). Parenteral nutrition was isocaloric and isonitrogenous. Infusions were administered at a rate of 2.0 mL/h over 5 days. Nutrition status was assessed by body weight change, plasma proteins, accumulated urinary creatinine, and nitrogen balance. RESULTS: Accumulated urinary creatinine increased significantly after day 4 in the ALA-GLN PN group, compared with the SPN group and the controls. Body weight change significantly differed on day 5 between the ALA-GLN PN and SPN groups. After 3 days, nitrogen balance was significantly lower and nitrogen retention higher in the ALA-GLN PN group when compared with the SPN group. Albumin and transferrin concentrations decreased significantly in the SPN group, but did not differ from the controls in the ALA-GLN PN group. CONCLUSIONS: Weight, plasma proteins, urinary accumulated creatinine, and nitrogen retention showed a better evolution in the group supplemented with the glutamine dipeptide when compared with the SPN group. Our results suggest a more suitable nutrition support in animals receiving L-alanyl-L-glutamine.     

谷氨酰胺对新生儿临床结局的影响

目的 评价肠内、肠外补充谷氨酰胺对新生儿临床结局的影响.方法 采用平行、随机、双盲、对照试验,将100例新牛儿随机分为5组,分别为对照组(常规肠外营养组)、肠外谷氨酰胺1组[肠外营养1组,在常规肠外营养中静脉补充谷氨酰胺0.3 g/(kg·d),其中谷氨酰胺取代了处方中相应氨基酸的量]、肠内谷氨酰胺Ⅰ组[肠内营养1组,口服添加谷氨酰胺0.3 g/(kg·d),谷氨酰胺取代了常规肠外营养中相应氨基酸的量]、肠外谷氨酰胺2组[肠外营养2组,在常规肠外营养中静脉补充谷氨酰胺0.3 g/(kg·d)]、肠内谷氨酰胺2组[肠内营养2组,口服添加谷氨酰胺0.3 g/(kg·d)],每组20例,对照组按照常规给予肠外营养支持,氨基酸的剂量按照中国新生儿营养支持临床应用指南给予[从1.0～2.0 g/(kg·d)开始,增至3.5 g/(kg·d)].首要终点指标为达到全肠内喂养日龄[标准配方摄入量≥120ml/(kg·d)]、胃潴留次数、完全脱离肠外营养时间和死亡率.次要终点指标为体重变化和头围变化、肝功能、肾功能、呼吸机应用天数、住院天数.结果 5组患儿达到全肠内喂养日龄、胃潴留次数及脱离肠外营养时间差异均无显著性.患儿肝肾功能水平及体重增长、头围增长、抗生素应用天数、住院天数差异均无显著性(P＞0.05).肠外谷氨酰胺1组和2组较对照组呼吸机应用天数显著减少(P＜0.05).死亡率通过意向性分析显示,与对照组比较,肠外谷氨酰胺1组RR为1.053,95%CI为0.952～1.164;肠内谷氨酰胺1组RR为1.333,95%CI为1.035～1.717;肠外谷氨酰胺2组RR为1.053,95%CI为0.952～1.164;肠内谷氨酰胺2组RR为1.25,95%CI为1.004～1.556.结论 补充谷氨酰胺未能缩短达到全肠内喂养天数、减少胃潴留次数、缩短全肠外营养应用时间;肠外补充谷氨酰胺可以减少新生儿呼吸机应用大数.新生儿肠外补充谷氨酰胺对患儿住院期间的死亡率无明显影响.     

Effect of enteral glutamine or glycine on whole-body nitrogen kinetics in very-low-birth-weight infants

BACKGROUND: Glutamine is a critical amino acid for the metabolism of enterocytes, lymphocytes, and other proliferating cells. Although supplementation with glutamine has been suggested for growing infants, its effect on protein metabolism has not been examined. OBJECTIVE: The objective was to examine the effect of enteral glutamine or glycine on whole-body kinetics of glutamine, phenylalanine, leucine, and urea in preterm infants. DESIGN: Infants at <32 wk of gestation were given formula supplemented with either glutamine (0.6 g. kg(-1). d(-1); n = 9) or isonitrogenous amounts of glycine (n = 9) for 5 d. Eight infants fed unsupplemented formula served as control subjects. Glutamine, phenylalanine, leucine nitrogen flux, leucine carbon flux, and urea kinetics were quantified during a basal fasting period and in response to nutrient intake. RESULTS: Growing preterm infants had a high weight-specific rate of appearance of glutamine, phenylalanine, and leucine nitrogen flux. When compared with the control treatment, enteral glutamine resulted in a high rate of urea synthesis, no change in the plasma glutamine concentration, and no change in the rate of appearance of glutamine. Glycine supplementation resulted in similar changes in nitrogen metabolism, but the magnitude of change was less than that in the glutamine group. In the nonsupplemented infants, the rate of appearance of leucine nitrogen flux was negatively correlated (rho = -0.72) with urea synthesis. In contrast, the correlation (rho = 0.75) was positive in the glutamine group. CONCLUSION: Enterally administered glutamine in growing preterm infants is entirely metabolized in the gut and does not have a discernable effect on whole-body protein and nitrogen kinetics.     

Évaluation nutritionnelle chez l'insuffisant rénal chronique hémodialysé

Malnutrition is common in patients with uremia, and is frequently latent. In hemodialysis patients, malnutrition can be critical, forming one of the main causes of mortality. Anthropomorphic measurements reveal a decrease in lean and fat body mass in respectively 30–50 and 70 % of these patients. The severity of malnutrition during chronic hemodialysis has led to a search for nutritional markers for use in identifying high-risk patients requiring active nutritional management; they include a serum transthyretin value of < 300 mg/l, a serum somatomedin C of < 300 μg/l and a protein catabolic rate of < 1 g/kg/l. Given their simplicity and low cost, serum transthyretin and the protein catabolic rate may be useful for monitoring such patients.     

Determination of glutamine in muscle protein facilitates accurate assessment of proteolysis and de novo synthesis-derived endogenous glutamine production.

BACKGROUND: Results of tracer studies indicate that skeletal muscle contributes to approximately 70% of overall glutamine production in healthy adults; the contribution of de novo synthesis being estimated at approximately 60%. However, measurement of the de novo synthesis rate in muscle tissue requires knowledge of the appearance rate of glutamine in plasma and the quantity of glutamine derived from intracellular proteolysis. Thus, the content of glutamine in muscle protein is a prerequisite for an accurate calculation. OBJECTIVE: The objective of the study was to measure glutamine in muscle protein. DESIGN: Muscle specimens (open biopsies) were obtained from humans (10 men and 4 women), rats (n = 4), cows (n = 4), and pigs (n = 4). Glutamine was assessed via prehydrolysis derivatization, rapid microwave-enhanced acid hydrolysis, and 5-dimethylaminonaphthalene-1-sulfonyl chloride (dansyl chloride) reversed-phase HPLC, and expressed per mg alkali-soluble protein (ASP) and DNA. RESULTS: Glutamine concentrations in muscle cell protein of various species ranged from 41 to 49 microg/mg ASP; the differences were not species related. The combined means (+/-SDs) for the 4 species were 43.6 +/- 4.9 microg/mg ASP and 11.9 +/- 2.0 mg/mg DNA, respectively. In humans, there was no apparent influence of age, sex, or BMI. CONCLUSIONS: Direct and specific measurements of glutamine in intact muscle protein were 50% lower than assumed previously. We used data compiled from earlier studies to recalculate the contributions of proteolysis and de novo synthesis to the endogenous production of glutamine in selected age groups of healthy humans; these contributions remained remarkably constant at approximately 13% and approximately 87%, respectively.     

谷氨酰胺与巨噬细胞的代谢及免疫调节作用

谷氨酰胺（Ｇｌｎ）是循环和体内氨基酸池中含量最丰富的氨基酸;创伤后机体免疫功能损害与血中谷氨酰胺浓度下降密切相关,单核巨噬细胞是免疫系统的组成部分,在免疫反应中起重要作用。研究表明谷氨酰胺是单核巨噬细胞主要的代谢底物,通过谷氨酰胺酵解途径,为细胞代谢提供能量,为细胞合成ＤＮＡ和ｍＲＮＡ提供嘌呤,嘧啶、核苷酸生物合成前体,提供氨基葡萄糖、ＧＴＰ和ＮＡＤ＾＋合成的氮前体。单核巨噬细胞的免疫功能依赖于谷     

Maintenance of Small Bowel Mucosa with Glutamine-Enriched Parenteral Nutrition

Glutamine is an important fuel utilized by the intestinal mucosa that is not present in standard amino acid nutrition solutions. In order to determine the effects of glutamine on the intestine, glutamine enriched nutrition was administered intravenously to male Wistar rats. A standard amino acid solution was enriched with 1 and 2 g/100 ml of glutamine or glycine and used as part of a parenteral nutrition regime for 7 days. Intestinal samples were taken for measurements of jejunal weight, DNA, protein, mucosal thickness and villus height. Animals receiving 2 g glutamine/100 ml in the nutrition solution had increased intestinal weight, DNA, and villus height when compared to animals receiving 2 g/100 ml of glycine. No increase in the intestinal parameters was noted when 1 g/100 ml of glutamine was used. To investigate the dose-response effects of glutamine, further studies were performed using iso-nitrogenous and isocaloric solutions containing 0, 2, and 3 g of glutamine/100 ml. Animals receiving glutamine had a significant increase in mucosal weight, DNA, protein and villus height when compared to animals receiving no glutamine in the parenteral solutions. There was a dose-response relationship between the increase in jejunal DNA and the increased intake of glutamine (r = 0.93, p < 0.01) but no correlation with the nitrogen content of the solutions (r = 0.18, p = 0.8). Total body nitrogen retention was greater in animals receiving 2 g/100 ml of glutamine (166 ± 12 mg, days 6/7) when compared to those receiving 0 and 3 g of glutamine/100 ml (126 ± 14 mg and 138 ± 16 mg, respectively, p < 0.05). These studies demonstrate that glutamine enriched nutrition protects against atrophy of the intestinal mucosa and when given at 2 g/100 ml improves nitrogen retention during intravenous feeding. (Journal of Parenteral and Enteral Nutrition 13: 579–585, 1989)     

谷氨酰胺对肝保护作用研究进展

谷氨酰胺(Gln)是人体含量最为丰富的氨基酸,在感染、外伤等重症状态下,Gln被大量消耗,出现相对缺乏的状态;同时,体内的抗氧化剂如谷胱甘肽含量明显降低.补充Gln能够增加肝谷胱甘肽的合成,提高抗氧化损伤的能力,保护肝组织.在肠外营养液中添加Gln可以增加肠道的能量供应和抗感染能力,减少细菌和内毒素移位对肝的影响;还可以促进高血糖素分泌,降低门静脉中胰岛素/高血糖素比例,从而减少肝内脂肪沉积.     

谷氨酰胺和生长激素对术后病人肌肉代谢的影响

目的许多研究表明,给予生长激素和谷氨酰胺能减少手术后肌肉蛋白的分解(术后肌蛋白分解表现在肌蛋白合成减少、谷氨酰胺水平降低和氮丢失增加)。本研究目的是联合使用生长激素和胰岛素样生长因子((IGF-I,一种能解释生长激素部分作用效果的生长因子)及添加生长激素和谷氨酰胺对术后肌肉代谢的影响。     

Studies of glutamine uptake across human skeletal sarcolemma

In the human body skeletal muscle is the largest store of glutamine, an important amino-acid in whole body nitrogen balance. Glutamine transport was measured in purified human skeletal muscle sarcolemmal vesicles (HMSV). The activity of sarcolemmal marker enzymes (K(+)-stimulated nitrophenylphosphatate (KpNPPase) and 5'-nucleotidase) was increased approximately 14-fold in the sarcolemmal fraction (SF) compared to the crude muscle homogenate (CH). Glutamine transport in HMSV was Na(+)-dependent (initial rate of 1 muM glutamine in the presence of 0.1 M NaCl = 7 (+/- 1.7) x 10(-3) pmol.mg(-1) protein.s(-1) compared to 1.5 (+/- 0.3) x 10(-3) pmol mg(-1) protein.s(-1) in the presence of 0.1 M Choline Cl). The rate of glutamine uptake into HMSV was increased in the presence of an inside negative membrane potential.     

择期手术／意外创伤后补充谷氨酰胺的效应

The etabolic response to injury,whether a controlled electivesurgical procedure or an accidental injury,is characterized by the breakdown of skeletal muscle protein and the translocation of the amino acids to visceral organs and the wound.At these sites the substrate serves to dnhance host defenses,and support vital organ function and wound repair.Glutamine (GLN) plays a major role in this process,accounting for approximately one-third of the translocated nitrogen.From the data available,GLN supplemented intravenous nutrition in patients undergoing elective surgery improved nitrogen balance,helped correct the decreased GLN concentration found in the free intracellular skeletal muscle amino acid pool and enhanced net protein synthesis (particularly in skeletal muscel).Six rancomized blinded trials(two multicentered investigations) have reported a dereased length in hospital stay in postoperative patients receiving GLN supplementation.Following blunt trauma,GLN supplementation increased plasma concentrations,attenuated the immunosuppression commonly observed and decreased the rate of infection.Patients with burn injury have low GLN plasma and intramuscular concentrations,but turnover and synthesis rate are accelerated,yet apparently inadequate to support normal concentrations.These data suggests that GLN supplementation has important effects in catabolic surgical patients,but the exact mechanisms to explain these events remain unknown and more research is required to explain the apparent benefits of dietary GLN.     

Sarcopénie des sujets âgés : libérez les acides aminés !

The underlying mechanisms of sarcopenia (i.e. the loss of muscle mass in aging) are still unknown. The primum movens seems to be a blunted anabolic response of muscle to dietary intake which could be related to a decreased systemic availability of amino acids. The latter could be linked to an increased amino acid metabolism in the splanchnic area. This splanchnic sequestration should be saturated by i) an increase in protein intake (global or in specific amino acids), ii) a modification of the rhythm of intake, or iii) the use of “fast” proteins. Alternatively (or in addition), the alteration of protein synthesis with advance in age could be located in the muscle, by decreasing the anabolic stimuli (e.g. insulin, GH, testosterone) or by increasing the catabolic environment (e.g. cortisol, pro-inflammatory cytokines).     

Effect of glutamine infusions on glutamine concentration and protein synthetic rate in rat muscle

Studies were undertaken in sedated and unsedated rats to raise the depleted intramuscular glutamine concentrations produced by aseptic abscesses, and to assess the effect of this change on muscle protein fractional synthetic rate. Age- and weight-matched control animals were also included in the study. The rats were infused for up to 5 hours via the lateral tail vein with 1 mL/100 g of body weight per hour of either saline or 0.22 M glutamine. The intramuscular concentration of glutamine (mmol/L of intracellular water), which was reduced by 45% after turpentine in the sedated animals, was restored to within 79% of control values, but the muscle fractional protein synthetic rate, which was also reduced by 41% in these animals, was not improved by the glutamine infusions. Glutamine administration also failed to increase muscle protein synthesis in unsedated rats and in those supplemented with a liquid meal. It is concluded that acute elevations in muscle glutamine concentrations do not increase protein synthesis in this tissue and that therefore glutamine is unlikely to be a mediator in the control of muscle protein synthesis under these circumstances.     

Glutamine as a key ingredient in protein metabolism]

Glutamine has a number of unique properties which suggest that this amino acid plays an important role in health and disease. Glutamine is considered a conditionally essential amino acid, because during periods of severe metabolic stress the body's requirements of glutamine may exceed the individual's ability to produce sufficient amounts of the amino acid. Studies with glutamine-enriched nutrition show beneficial effects on nitrogen balance, muscle protein metabolism, gastrointestinal mucosa, and immune status. In certain patient categories addition of glutamine reduces the number of infectious complications, improves long-term survival, and shortens hospital stay, e.g. bone marrow transplantation patients, neonates with severely subnormal weight, patients with multiple organ failure, multi-trauma patients. More studies are needed to document the dose-response and to identify the patients that are likely to benefit from glutamine supplementation.     

Effect of intermittent glutamine supplementation on skeletal muscle is not long-lasting in very old rats

Background and objective

Muscle is the major site for glutamine synthesis via glutamine synthetase (GS). This enzyme is increased 1.5–2 fold in 25–27-mo rats and may be a consequence of aging-induced stress. This stimulation is similar to the induction observed following a catabolic state such as glucocorticoid treatment (6 to 24 months). Although oral glutamine supply regulates the plasma glutamine level, nothing is known if this supplementation is interrupted before the experiment.

Design

Adult (8-mo) and very old (27-mo) female rats were exposed to intermittent glutamine supplementation for 50 % of their age lifetime. Treated rats received glutamine added to their drinking water and control rats water alone but the effect of glutamine supplementation was only studied 15 days after the last supplementation.

Results

Glutamine pretreatment discontinued 15 days before the experiment increased plasma glutamine to ～ 0.6 mM, a normal value in very old rats. However, it failed to decrease the up-regulated GS activity in skeletal muscle from very old rats.

Conclusion

Our results suggest that long-term treatment with glutamine started before advanced age but discontinued 15 days before rat sacrifice is effective in increasing plasma glutamine to recover basal adult value and in maintaining plasma glutamine in very old rats, but has no long-lasting effect on the GS activity of skeletal muscle with advanced age.     

Oral glutamine and amino acid supplementation inhibit whole-body protein degradation in children with Duchenne muscular dystrophy

BACKGROUND: Glutamine has been shown to acutely decrease whole-body protein degradation in Duchenne muscular dystrophy (DMD). OBJECTIVE: To improve nutritional support in DMD, we tested whether oral supplementation with glutamine for 10 d decreased whole-body protein degradation significantly more than did an isonitrogenous amino acid control mixture. DESIGN: Twenty-six boys with DMD were included in this randomized, double-blind parallel study; they received an oral supplement of either glutamine (0.5 g . kg(-1) . d(-1)) or an isonitrogenous, nonspecific amino acid mixture (0.8 g . kg(-1) . d(-1)) for 10 d. The subjects in each group were not clinically different at entry. Leucine and glutamine metabolisms were estimated in the postabsorptive state by using a primed continuous intravenous infusion of [1-(13)C]leucine and [2-(15)N]glutamine before and 10 d after supplementation. RESULTS: A significant effect of time was observed on estimates of whole-body protein degradation. A significant (P < 0.05) decrease in the rate of leucine appearance (an index of whole-body protein degradation) was observed after both glutamine and isonitrogenous amino acid supplementation [x +/-SEM: 136 +/- 9 to 124 +/- 6 micromol . kg fat-free mass (FFM)(-1) . h(-1) for glutamine and 136 +/- 6 to 131 +/- 8 micromol . kg FFM(-1) . h(-1) for amino acids]. A significant (P < 0.05) decrease in endogenous glutamine due to protein breakdown was also observed (91 +/- 6 to 83 +/- 4 micromol . kg FFM(-1) . h(-1) for glutamine and 91 +/- 4 to 88 +/- 5 micromol . kg FFM(-1) . h(-1) for amino acids). The decrease in the estimates of whole-body protein degradation did not differ significantly between the 2 supplemental groups. CONCLUSION: Oral glutamine or amino acid supplementation over 10 d equally inhibits whole-body protein degradation in DMD.     

Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and ω‐3 Polyunsaturated Fatty Acids

Background: Doxorubicin (DOX) has been one of the most effective antitumor agents against a broad spectrum of malignancies. However, DOX‐induced cardiotoxicity forms the major cumulative dose‐limiting factor. Glutamine and ω‐3 polyunsaturated fatty acids (PUFAs) are putatively cardioprotective during various stresses and/or have potential chemosensitizing effects during cancer chemotherapy. Methods: Antitumor activity and cardiotoxicity of DOX treatment were evaluated simultaneously in a MatBIII mammary adenocarcinoma tumor‐bearing rat model treated with DOX (cumulative dose 12 mg/kg). Single or combined treatment of parenteral glutamine (0.35 g/kg) and ω‐3 PUFAs (0.19 g/kg eicosapentaenoic acid and 0.18 g/kg docosahexaenoic acid) was administered every other day, starting 6 days before chemotherapy initiation until the end of study (day 50). Results: Glutamine alone significantly prevented DOX‐related deterioration of cardiac function, reduced serum cardiac troponin I levels, and diminished cardiac lipid peroxidation while not affecting tumor inhibition kinetics. Single ω‐3 PUFA treatment significantly enhanced antitumor activity of DOX associated with intensified tumoral oxidative stress and enhanced tumoral DOX concentration while not potentiating cardiac dysfunction or increasing cardiac oxidative stress. Intriguingly, providing glutamine and ω‐3 PUFAs together did not consistently confer a greater benefit; conversely, individual benefits on cardiotoxicity and chemosensitization were mostly attenuated or completely lost when combined. Conclusions: Our data demonstrate an interesting differentiality or even dichotomy in the response of tumor and host to single parenteral glutamine and ω‐3 PUFA treatments. The intriguing glutamine × ω‐3 PUFA interaction observed draws into question the common assumption that there are additive benefits of combinations of nutrients that are beneficial on an individual basis.