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Glutamine
Glutamine/Drug Interactions
Anesthetics
Anesthetics: General anesthesia resulted in a decrease in muscle glutamine in human research (
125
).
Antibiotics
Antibiotics: Glutamine in postsurgical, catabolic, or exercising individuals reduced the rate of infection (
104
;
97
;
126
;
84
). In burn or critically ill patients, glutamine supplementation resulted in a reduced incidence of Gram-negative bacteremia, positive blood cultures in general, and septic complications (
58
;
12
;
75
;
8
;
7
). Glutamine had no effect on antibiotic use in various clinical trials (
77
;
9
).
Anticachexic agents
Anticachexic agents: In patients with cancer or HIV-related cachexia, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased weight gain and fat free mass (
53
;
41
). This was attributed to decreased muscle protein breakdown and improved muscle protein synthesis.
Antidepressants
Antidepressants: In human research, antidepressant treatment was associated with increased serum glutamine (
35
).
Antidiarrheals
Antidiarrheals: In human research, glutamine induced an increase in water and electrolyte absorption or reduced secretion (
127
;
31
). Reduced gut permeability has been shown in other glutamine-supplementation studies (
128
;
129
;
130
;
131
;
132
). Reduced diarrhea has been shown in clinical studies (
63
;
115
;
80
). Loperamide intake was reduced in glutamine-supplemented colorectal cancer patients treated with 5-fluorouracil and folinic acid (
85
).
Anti-inflammatory agents
Anti-inflammatory agents: In postoperative patients, parenteral glutamine decreased systemic inflammation (
133
;
21
).
Antiretroviral agents
Antiretroviral agents: In human research, glutamine reduced the severity of antiretroviral agent-associated diarrhea (
80
;
134
;
135
) and increased blood levels of antiretroviral agents (
135
).
Celecoxib
Celecoxib: In human research, a combination of celecoxib and glutamine had no effect on the toxicities of leucovorin (
136
).
Chemoprotectants
Chemoprotectants: Glutamine 10g orally three times daily for four days starting 24 hours after completion of paclitaxel resulted in a reduction in the severity of peripheral neuropathy (
137
). Various human studies suggest that glutamine is associated with a reduction in side effects associated with chemotherapy (
138
;
14
;
16
;
15
;
88
;
90
). In human research, a combination of celecoxib and glutamine had no effect on the toxicities of leucovorin (
136
).
Growth hormones
Growth hormones: In human research, a glutamine-containing supplement increased serum growth hormone levels (
32
;
39
). Treatment of patients with chronic illness with human growth hormone normalized plasma or muscle glutamine levels (
139
;
140
). In recent surgical patients, combination of glutamine with growth hormone and IGF-1 resulted in a net protein gain over glutamine alone, suggesting a combination effect (
2
). In patients with short bowel syndrome, a combination of growth hormone and glutamine had additive effects (
69
;
70
). Growth hormone stimulated glutamine transport across the brush border membrane in human research (
141
). However, infusion into the femoral artery decreased glutamine release from muscle and decreased de novo synthesis of muscle glutamine (
142
). The relationship of glutamine and growth hormone has been discussed by others (
143
).
Immunosuppressants
Immunosuppressants: In human research, parenteral and enteral glutamine were associated with modifications in systemic interleukin and endotoxin production or human leukocyte antigen-DR expression on monocytes, and improvements in lymphocyte recovery (
22
;
144
;
145
;
146
;
128
;
147
;
3
;
148
). Plasma glutamine was associated with the production of tumor necrosis factor (TNF) and IL-2 (
48
). In human and animal research, glutamine increased immunoglobulin levels in plasma and nasal fluids (
17
;
18
;
19
).
Insulin
Insulin: Glutamine levels were increased in insulin treated patients with abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and reperfusion (
66
). Fasting insulin levels increased in cystic fibrosis patients using oral glutamine (
67
). Glutamine increased insulin-mediated glucose disposal in trauma patients (
68
).
Interferon-alpha
Interferon-alpha: In human research, the combination of interferon-alpha and a glutamine-derived agent, murabutide, appeared to have beneficial effects on anti- and proinflammatory cytokines (
149
). In recent surgical patients, combination of glutamine with growth hormone and IGF-1 resulted in a net protein gain over glutamine alone, suggesting a combination effect (
2
).
Methotrexate
Methotrexate: Methotrexate was suggested to be the cause for a lack of effect of glutamine in allogeneic bone marrow patients (
9
).
Neuroleptics
Neuroleptics: In human research, glutamine decreased the dose of neuroleptics required in hospital inpatients (
47
).
Nonsteroidal anti-inflammatory agents (NSAIDs)
Nonsteroidal anti-inflammatory agents (NSAIDs): In human research, glutamine reduced intestinal permeability induced by indomethacin (
150
), but not aspirin (
151
). In animal research, glutamine ameliorated indomethacin-induced intestinal damage, including reduced oxidative stress (
152
).
Opiates
Opiates: In children undergoing stem cell transplantation, use of narcotics was decreased in those children receiving glutamine (
92
).
Protein sparing agents
Protein sparing agents: Glutamine has protein-sparing or improved-nitrogen-balance effects in infants, and nonhealthy children and adults (
153
;
154
;
155
;
156
;
103
;
3
;
18
;
105
;
1
;
118
;
157
;
8
;
7
).
Somatostatin
Somatostatin: Somatostatin had no effect on plasma glutamine levels (
158
).
Sulpiride
Sulpiride: Sulpiride had no effect on serum levels of glutamine (
159
).
Valproic acid
Valproic acid: In human research, there was some evidence to suggest valproate therapy is associated with increased brain levels of glutamine (
160
).
Glutamine/Herb/Supplement Interactions:
Antibacterials
Antibacterials: Glutamine in postsurgical, catabolic, or exercising individuals reduced the rate of infection (
104
;
97
;
126
;
84
). In burn or critically ill patients, glutamine supplementation resulted in a reduced incidence of Gram-negative bacteremia, positive blood cultures in general, and septic complications (
58
;
12
;
75
;
8
;
7
). Glutamine had no effect on antibiotic use in various clinical trials (
77
;
9
).
Anticachexic herbs and supplements
Anticachexic herbs and supplements: In patients with cancer or HIV-related cachexia, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased weight gain and fat free mass (
53
;
41
). This was attributed to decreased protein breakdown and improved protein synthesis.
Antidepressants
Antidepressants: In human research, antidepressant treatment was associated with increased serum glutamine (
35
).
Antidiarrheals
Antidiarrheals: In human research, glutamine induced an increase in water and electrolyte absorption or reduced secretion (
127
;
31
). Reduced gut permeability has been shown in other glutamine-supplementation studies (
128
;
129
;
130
;
131
;
132
). Reduced diarrhea has been shown in clinical studies (
63
;
115
).
Anti-inflammatory herbs
Anti-inflammatory herbs: In postoperative patients, parenteral glutamine decreased systemic inflammation (
133
;
21
).
Antioxidants
Antioxidants: A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (
161
).
Antiretroviral herbs
Antiretroviral herbs: In human research, glutamine reduced the severity of antiretroviral agent-associated diarrhea (
80
;
134
;
135
) and increased blood levels of antiretroviral agents (
135
).
Arginine
Arginine: A combination of beta-hydroxy-beta-methylbutyrate (BHMB), glutamine, and arginine was studied for rheumatoid arthritis and was well tolerated (
28
). A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (
161
). A combination of omega-3 fatty acids, arginine, and glutamine was well tolerated and improved levels of serum protein and immunological response (
162
;
163
).
Beta-hydroxy-beta-methylbutyrate (BHMB)
Beta-hydroxy-beta-methylbutyrate (BHMB): In human research, a combination of BHMB, glutamine, and arginine was studied for rheumatoid arthritis and was well tolerated (
28
).
Branched-chain amino acids
Branched-chain amino acids: In human research, a combination of carbohydrates and branched-chain amino acids increased plasma glutamine during exercise over carbohydrate alone (
164
). Branched-chain amino acids resulted in an increase in muscle and plasma glutamine production during exercise (
165
;
166
;
167
;
168
;
169
).
Chemotherapeutic herbs and supplements
Chemotherapeutic herbs and supplements: Glutamine 10g orally three times daily for four days starting 24 hours after completion of paclitaxel resulted in a reduction in the severity of peripheral neuropathy (
137
). Various human studies suggest that glutamine is associated with reduction in side effects associated with chemotherapy (
138
;
14
;
16
;
15
;
88
;
90
).
Exercise performance herbs and supplements
Exercise performance herbs and supplements: In human research, strenuous exercise decreased plasma levels of glutamine (
170
). Glutamine supplementation promoted storage of muscle glycogen following exercise, to a similar extent as oral glucose polymer (
36
), and enhanced exercise-induced IL-6 production (
20
). Glutamine increased body mass, lean body mass, and initial rate of power production in exercising adults (
171
). In a review, Ohtani discussed the beneficial effects of dietary amino acid supplementation, including glutamine, on muscle function, fatigue, and recovery in exercising athletes (
45
).
Fiber
Fiber: A combination of probiotics, fiber, and glutamine reduced diarrhea associated with antiretrovirals (
134
).
Growth hormones
Growth hormones: In human research, a glutamine-containing supplement increased serum growth hormone levels (
32
;
39
). Treatment of patients with chronic illness with human growth hormone normalized plasma or muscle glutamine levels (
139
;
140
). In recent surgical patients, combination of glutamine with growth hormone and IGF-1 resulted in a net protein gain over glutamine alone, suggesting a combination effect (
2
). In patients with short bowel syndrome, a combination of growth hormone and glutamine had additive effects (
69
;
70
). Growth hormone stimulated glutamine transport across the brush border membrane in human research (
141
). However, infusion into the femoral artery decreased glutamine release from muscle and decreased de novo synthesis of muscle glutamine (
142
). The relationship of glutamine and growth hormone has been discussed by others (
143
).
Immunostimulants
Immunostimulants: In human research, parenteral and enteral glutamine were associated with modifications in systemic interleukin and endotoxin production or human leukocyte antigen-DR expression on monocytes, and improvements in lymphocyte recovery (
22
;
144
;
145
;
146
;
128
;
147
;
3
;
148
). Plasma glutamine was associated with the production of tumor necrosis factor (TNF) and IL-2 (
48
). In human and animal research, glutamine increased immunoglobulin levels in plasma and nasal fluids (
17
;
18
;
19
).
Immunosuppressants
Immunosuppressants: In human research, parenteral and enteral glutamine were associated with modifications in systemic interleukin and endotoxin production or human leukocyte antigen-DR expression on monocytes, and improvements in lymphocyte recovery (
22
;
144
;
145
;
146
;
128
;
147
;
3
;
148
). Plasma glutamine was associated with the production of tumor necrosis factor (TNF) and IL-2 (
48
). In human and animal research, glutamine increased immunoglobulin levels in plasma and nasal fluids (
17
;
18
;
19
).
Insulin-modifying herbs and supplements
Insulin-modifying herbs and supplements: Glutamine levels were increased in insulin-treated patients with abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and reperfusion (
66
). Fasting insulin levels increased in cystic fibrosis patients using oral glutamine (
67
). Glutamine increased insulin-mediated glucose disposal in trauma patients (
68
).
Narcotics
Narcotics: In children undergoing stem cell transplantation, use of narcotics was decreased in those children receiving glutamine (
92
).
Neuroleptics
Neuroleptics: In human research, glutamine decreased the dose of neuroleptics required in hospital inpatients (
47
).
Omega-3 fatty acids
Omega-3 fatty acids: A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (
161
). A combination of omega-3 fatty acids, arginine, and glutamine was well tolerated and improved levels of serum protein and immunological response (
162
;
163
).
Ornithine alpha-ketoglutarate (OKG)
Ornithine alpha-ketoglutarate (OKG): In burn and trauma patients, OKG induced an increase in plasma glutamine (
172
;
173
).
Probiotics
Probiotics: A combination of probiotics, fiber, and glutamine reduced diarrhea associated with antiretrovirals (
134
). A combination of probiotics and glutamine in enteral feeding reduced the infection rate and length of stay in critical care (
27
).
Protein-sparing herbs and supplements
Protein-sparing herbs and supplements: Glutamine has protein-sparing or improved-nitrogen-balance effects in infants, and nonhealthy children and adults (
153
;
154
;
155
;
156
;
103
;
3
;
18
;
105
;
1
;
118
;
157
;
8
;
7
).
Weight-promoting herbs and supplements
Weight-promoting herbs and supplements: In patients with cancer-related cachexia, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased weight gain and fat free mass, which was maintained for approximately six months (
53
). This was attributed to decreased protein breakdown and improved protein synthesis. Weight gain was also increased in chemotherapy-treated cancer patients given glutamine (
101
).
Wound-healing herbs and supplements
Wound-healing herbs and supplements: In burn patients, glutamine improved wound healing (
10
). In human research, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased collagen deposition, as reflected by hydroxyproline content, but had no effect on total protein accumulation (
54
).
Glutamine/Food Interactions:
Antioxidant-containing foods
Antioxidant-containing foods: A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (
161
).
Carbohydrate
Carbohydrate: During exercise, carbohydrate maintained plasma glutamine (
174
;
175
). During exercise, a low-carbohydrate diet resulted in decreased plasma glutamine in untrained men (
176
).
Fiber
Fiber: Reduced diarrhea has been shown in clinical studies (
63
;
115
). A combination of probiotics, fiber, and glutamine reduced diarrhea associated with antiretrovirals (
134
).
Fish
Fish: A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (
161
). A combination of omega-3 fatty acids, arginine, and glutamine was well tolerated and improved levels of serum protein and immunological response (
162
;
163
).
Fructose
Fructose: In healthy children, fructose absorption was enhanced by dietary glutamine (
177
).
Monosodium glutamate
Monosodium glutamate: Monosodium glutamate consumption by adults increased plasma glutamine (
178
).
Probiotic-containing foods
Probiotic-containing foods: A combination of probiotics, fiber, and glutamine reduced diarrhea associated with antiretrovirals (
134
). A combination of probiotics and glutamine in enteral feeding reduced the infection rate and length of stay in critical care (
27
).
Protein
Protein: A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (
161
). A combination of omega-3 fatty acids, arginine, and glutamine was well tolerated and improved levels of serum protein and immunological response (
162
;
163
). Branched-chain amino acids resulted in an increase in muscle and plasma glutamine production during exercise (
165
;
166
;
167
;
168
;
169
). Glutamine has protein sparing or improved nitrogen balance effects in infants, and nonhealthy children and adults (
153
;
154
;
155
;
156
;
103
;
3
;
18
;
105
;
1
;
118
;
157
;
8
;
7
).
Weight promoting diets
Weight promoting diets: In patients with cancer-related cachexia, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased weight gain and fat free mass, which was maintained for approximately six months (
53
). This was attributed to decreased protein breakdown and improved protein synthesis. Weight gain was also increased in chemotherapy-treated cancer patients given glutamine (
101
).
Glutamine/Lab Interactions:
Amino acids
Amino acids: In human study, glutamine supplementation alters levels of other amino acids, including a decrease in glycine, proline, and arginine (
179
), or an increase in glycine, arginine, alanine, or ornithine (
180
;
51
;
181
). In human and animal study, glutamine supplementation increased plasma taurine (
182
). In human study, nonessential amino acids do not appear to increase following glutamine supplementation (
183
). Other studies show no effect on amino acids in general (
184
). Fish determined that glutamine-enriched tube feeding and TPN can result in similar profiles for most plasma amino acids at carefully matched doses (
185
).
Ammonia
Ammonia: In cirrhotic patients without transjugular intrahepatic portosystemic shunts, an oral glutamine load caused an increase in ammonia (
64
).
Antiretroviral agents
Antiretroviral agents: In human study, glutamine increases blood levels of antiretroviral agents (
135
).
Aspartate
Aspartate: In human study, glutamine supplementation increased plasma aspartate (
181
).
Bicarbonate
Bicarbonate: In human study, glutamine supplementation increased levels of plasma bicarbonate (
39
)
Blood cultures
Blood cultures: In burn or critically ill patients, glutamine supplementation resulted in a reduced incidence of Gram-negative bacteremia, positive blood cultures in general, or septic complications (
58
;
12
;
75
;
8
;
7
).
Body mass
Body mass: In patients with cancer or HIV-related cachexia, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased weight gain and fat free mass (
53
;
41
). Glutamine increased body mass, lean body mass, and the initial rate of power production in exercising adults (
171
).
Cholinesterase
Cholinesterase: In human research, glutamine increased blood levels of cholinesterase (
23
).
Citrulline
Citrulline: In human research, glutamine supplementation increased plasma citrulline (
181
).
C-reactive protein
C-reactive protein: In human research, glutamine decreased levels of C-reactive protein (
23
;
58
).
D-xylose
D-xylose: In human research, glutamine supplementation increased levels of serum D-xylose as well as its excretion (
186
).
Electrocardiogram
Electrocardiogram: In human research, a single oral dose of glutamine resulted in a delayed time of onset of a more than 1.0mm of ST segment depression by 38 seconds (
43
).
Endotoxin
Endotoxin: In human research, glutamine supplementation reduced blood levels of endotoxin (
72
;
130
).
Free fatty acid
Free fatty acid: In human research, glutamine supplementation decreased plasma free fatty acids (
181
).
Glucose
Glucose: Glutamine increased insulin-mediated glucose disposal in trauma patients (
68
) and altered glucose homeostasis during and after exercise (
187
). In animal research, glutamine induced insulin resistance in adipose tissue, improving insulin signaling in liver and muscle (
188
). Also, increased glutamine availability blunted the effect of insulin action on glucose production and enhanced insulin-mediated glucose utilization (
189
).
Glutamate
Glutamate: In human research, glutamine supplementation increased plasma glutamate (
181
).
Glutamine
Glutamine: In human research, glutamine supplementation resulted in increases in glutamine in some (
2
;
95
;
5
;
71
;
179
;
3
;
72
;
105
;
36
;
190
;
51
;
181
;
107
) but not all (
19
;
59
;
39
;
191
) studies. In human research, gut mucosal and muscle glutamine also increased with supplementation (
192
;
193
). In animal research, glutamine increased muscle and plasma glutamine, but not tumor levels of glutamine (
129
).
Glycerol
Glycerol: In human research, glutamine supplementation decreased plasma glycerol (
181
).
Growth hormone
Growth hormone: In human research, a glutamine-containing supplement increased serum growth hormone levels (
32
;
39
;
39
).
Heart rate
Heart rate: In human research, glutamine reduced resting heart rate (
130
).
Immunoglobulins
Immunoglobulins: In human and animal research, glutamine increased immunoglobulin levels in plasma and nasal fluids (
17
;
18
;
19
). One study found no effect of glutamine on levels of sIgA (
115
).
Insulin
Insulin: Fasting insulin levels increased in cystic fibrosis patients using oral glutamine (
67
).
Insulin-like growth factor
Insulin-like growth factor: In human research, the effect of glutamine on insulin-like growth factor was studied (
33
).
Interleukins
Interleukins: In human research, glutamine supplementation enhanced exercise-induced IL-6 production (
20
) and decreased IL-6 in surgical patients (
21
;
22
). Glutamine was associated with the production of tumor necrosis factor (TNF) and IL-2 (
48
). Glutamine had no effect on serum levels of IL-8 (
115
;
22
) nor reduced IL-8 (
148
;
144
). In other research, glutamine had no effect on IL-6 or TNF (
148
;
144
).
Measures of oxidative stress
Measures of oxidative stress: In human research, glutamine reduced levels of diamine oxidase and malondialdehyde (
130
). In human research, glutamine supplementation resulted in maintenance of presurgical levels of total and reduced muscle glutathione (
26
).
Methotrexate levels
Methotrexate levels: In animal research, glutamine was associated with increased levels of methotrexate in the tumor and decreased levels in the gut (
194
).
Muscle glycogen
Muscle glycogen: In human research, glutamine supplementation promoted storage of muscle glycogen following exercise, to a similar extent as oral glucose polymer (
36
). Glutamine had no effect on muscle glycogen in other studies (
195
).
Nitrogen balance
Nitrogen balance: Glutamine had protein-sparing or improved-nitrogen-balance effects in infants, and nonhealthy children and adults (
153
;
154
;
155
;
156
;
103
;
3
;
18
;
105
;
1
;
118
;
157
;
8
;
7
;
107
). In human research, glutamine supplementation decreased urinary nitrogen and urinary 3-methylhistidine (
11
;
71
). In human research, glutamine had no effect on urinary nitrogen or nitrogen balance (
196
).
Proteins
Proteins: In human research, glutamine has been shown to increase levels of albumin, prealbumin, and transferrin (
23
;
11
;
58
;
71
). Other studies in humans found that glutamine had a lack of an effect on serum protein levels (
196
).
Temperature
Temperature: In human research, glutamine reduced body temperature (
130
).
Urinary ammonium
Urinary ammonium: Urinary ammonium increased in glutamine supplemented healthy individuals, but not patients with renal disease (
44
).
Urinary lactulose:mannitol (L:M) ratio
Urinary lactulose:mannitol (L:M) ratio: In human research, glutamine supplementation decreased the urinary lactulose:mannitol ratio (
130
).
White blood cell count
White blood cell count: In human research, glutamine reduced levels of white blood cells (
130
). In human research, glutamine supplementation increased lymphocyte count, with an increase in CD3+, CD4+, and CD8+, and normalization of the CD16+CD56+ subset (
14
;
23
;
3
;
24
;
197
).