IMPROVEMENT OF INTESTINAL PERMEABILITY WITH ALANYL-GLUTAMINE IN HIV PATIENTS:

Randomized double-blinded, placebo-controlled study using isonitrogenous doses of alanyl-glutamine (24 g/day) and placebo (glycine, 25 g/day) during 10 days. Before and after this nutritional supplementation lactulose and mannitol urinary excretion were determined by high performance liquid chromatography.

Results

Forty six patients with HIV/AIDS, 36 of whom were male, with 37.28 ± 3 (mean ± standard error) years were enrolled. Twenty two and 24 subjects were treated with alanyl-glutamine and with glycine respectively. In nine patients among all in the study protocol that reported diarrhea in the 14 days preceding the beginning of the study, mannitol urinary excretion was significantly lower than patients who did not report this symptom [median (range): 10.51 (3.01–19.75) vs. 15.37 (3.93–46.73); P = 0.0281] and lactulose/mannitol ratio was significantly higher [median (range): 0.04 (0.00–2.89) vs. 0.02 (0.00–0.19); P = 0.0317]. There was also a significant increase in mannitol urinary excretion in the group treated with alanyl-glutamine [median (range): 14.38 (8.25–23.98) before vs 21.24 (6.27–32.99) after treatment; n = 14, P = 0.0382].

Conclusion

Our results suggest that the integrity and intestinal absorption are more intensely affected in patients with HIV/AIDS who recently have had diarrhea. Additionally, nutritional supplementation with alanyl-glutamine was associated with an improvement in intestinal absorption.

Intestinal absorption; Glutamine; HIV; Placebos

Parameters	All	Study groups		P
Parameters	n = 46	Placebo GLY ^a a GLY = glycine (placebo) – GLY (25 g/day) was given with orange juice for 10 days, beginning on the 1st day of the study protocol n = 24	AG ^b b AG = alanyl-glutamine - AG (24 g/day) was given with orange juice for 10 days, beginning on the 1st day of the study protocol n = 22	P
Age in years (Mean ± SE)	37.28 ± 3.00	40.13 ± 1.89	34.18 ± 1.66	0.024^* * P = 0.024 comparing the mean age between AG group and the GLY (placebo) group using the Student t test
Gender
Male, n (%)	36 (78.3)	17 (70.8)	19 (86.4)	NS
Female, n (%)	10 (21.7)	7 (29.2)	3 (13.6)	NS
Clinical classification ^c c CDC (1993)(7)
A, n (%)	15 (32.6)	7 (29.2)	8 (36.4)	NS
B, n (%)	3 (6.5)	1 (4.2)	2 (9.1)	NS
C, n (%)	28 (60.9)	16 (66.6)	12 (54.5)	NS
CD4/mm³, n (Mean ± SE)	44 (384.5 ± 16.47)	24 (409.5 ± 64.9)	20 (354.4 ± 46.0)	NS
<200, n (%)	12 (27.3)	7 (29.2)	5 (25.0))	NS
≥200, n (%)	32 (72.7)	17 (70.8)	15 (75.0)	NS
VL (log₁₀), n (Mean ± SE)	37 (4.08 ± 1.05)	22 (4.08 ± 1.11)	15 (4.05 ± 0.99)	NS
HAART
Yes, n (%)	38 (82.6)	22 (91.7)	16 (72.7)	NS
No, n (%)	8 (17.4)	2 (8.3)	6 (27.3)	NS
Weight, n (Median ± SE)	46 (60.9 ± 3.3)	24 (60.7 ± 2.4)	22 (62.2 ± 2.1)	NS
BMI , n (Median ± SE)	46 (22.9 ± 1.9)	24 (22.3 ± 0.7)	22 (22.4 ± 0.8)	NS
Diarrhea (last 14 days)
Yes, n (%)	9 (19.6)	6 (25.0)	3 (13.6)	NS
No, n (%)	37 (80.4)	18 (75.0)	19 (86.4)	NS

Intestinal permeability test parameters median (range)	Treatment group or clinical status		P
	Placebo GLY^a a GLY = Glycine (placebo) – GLY (25 g/day) was given with orange juice for 10 days, beginning on the 1st day of the study protocol (n = 24)	AG ^b b AG = alanyl-glutamine - AG (24 g/day) was given with orange juice for 10 days, beginning on the 1st day of the study protocol (n = 22)
% of lactulose excretion	0.32 (0.00–8.71)	0.30 (0.00–3.82)	NS
% of mannitol excretion	16.10 (3.01–46.70)	13.70 (5.30–31.60)	NS
Lactulose/mannitol ratio	0.02 (0.00–2.89)	0.02 (0.00–0.19)	NS
	Diarrhea reported in the last 14 days (n = 9)	No diarrhea reported in the last 14 days (n = 36)
% of lactulose excretion	0.86 (0.00–8.71)	0.29 (0.00–3.82)	0.0318^* * P = 0.0318 and P = 0.0261 comparing groups that reported and did not report diarrhea in the last 14 days at baseline, using the Student t test, for urinary excretion of lactulose (%) and for lactulose/mannitol ratio respectively
% of mannitol excretion	11.70 (3.01–22.20)	15.35 (3.90–46.70)	NS
lactulose/mannitol ratio	0.05 (0.00–2.89)	0.02 (0.00–0.19)	0.0261^* * P = 0.0318 and P = 0.0261 comparing groups that reported and did not report diarrhea in the last 14 days at baseline, using the Student t test, for urinary excretion of lactulose (%) and for lactulose/mannitol ratio respectively
	Without HAART (n = 8)	HAART use (n = 37)
% of lactulose excretion	0.33 (0.10–1.01)	0.29 (0.00–8.71)	NS
% of mannitol excretion	17.05 (5.30–43.60)	14.00 (3.01–46.70)	NS
Lactulose/mannitol ratio	0.03 (0.00–0.19)	0.02 (0.00–2.89)	NS
	CD4 <200/mm³ (n = 12)	CD4 ≥200/mm³ (n = 31)
% of lactulose excretion	0.32 (0.00–1.38)	0.32 (0.00–8.71)	NS
% of mannitol excretion	13.60 (6.40–46.70)	14.50 (3.01–43.60)	NS
Lactulose/mannitol ratio	0.02 (0.00–0.22)	0.02 (0.00–2.89)	NS
	BMI <18.5 (n = 4)	BMI ≥18.5 (n = 42)
% of lactulose excretion	0.67 (0.42–1.16)	0.29 (0.00–8.71)	NS
% of mannitol excretion	12.50 (5.40–31.60)	14.50 (3.01–46.70)	NS
lactulose/mannitol ratio	0.07 (0.01–0.13)	0.02 (0.00–2.89)	NS

Parameters	Treatment group
Parameters	Placebo glycyne ^a a GLY = Glycine (placebo) – GLY (25 g/day) was given with orange juice for 10 days, beginning on the 1st day of the study protocol		Alanyl-glutamine ^b b AG = alanyl-glutamine - AG (24 g/day) was given with orange juice for 10 days, beginning on the 1st day of the study protocol
Weight (kg)	n = 20	P	n = 17	P
Before (mean ± SE)	60.64 ± 2.59	NS	63.08 ± 2.04	NS
After (mean ± SE)	62.66 ± 2.82		63.82 ± 1.98
BMI	n = 20		n = 17
Before (mean ± SE)	23.75 ± 0.82	NS	22.62 ± 0.87	NS
After (mean ± SE)	23.73 ± 0.99		22.87 ± 0.86
CD4 (/mm³)	n = 19		n = 17
Before (mean ± SE)	421.26 ± 75.84	NS	384.88 ± 48.48	NS
After (mean ± SE)	278.45 ± 63.88		412.00 ± 54.97
HIV viral load (log₁₀)	n = 19		n = 9
Before (mean ± SE)	4.04 ± 0.56	NS	4.07 ± 0.99	NS
After (mean ± SE)	3.86 ± 0.63		3.71 ± 0.72
% of lactulose excretion	n = 19		n = 14
Before, median (range)	0.28 (0.00–1.15)	NS	0.21 (0.00–3.82)	NS
After, median (range)	0.29 (0.00–3.95)		0.26 (0.00–1.17)
% of mannitol excretion	n = 19		n = 14
Before, median (range)	16.79 (3.93–46.73)	NS	14.38 (8.25–23.98)	0.0382^* * P = 0.0382 comparing the percentage of mannitol urinary excretion before and after treatment in AG group, using paired Student t test
After, median (range)	17.47 (0.00–47.51)		21.24 (6.27–32.99)
Lactulose/mannitol ratio	n = 19		n = 14
Before, median (range)	0.02 (0.00–0.12)	NS	0.02 (0.00–0.19)	NS
After, median (range)	0.02 (0.00–0.24)		0.01 (0.00–0.41)

Parameters	Treatment groups
	Placebo glycine ^a a GLY = Glycine (placebo) – GLY (25 g/day) was given with orange juice for 10 days, beginning on the 1st day of the study protocol (n = 24)		Alanyl-glutamine ^b b AG = alanyl-glutamine - AG (24 g/day) was given with orange juice for 10 days, beginning on the 1st day of the study protocol (n = 22)		Total (n = 46)
	n	%	n	%	n	%
Adverse event ^c c,d P > 0.05 comparing treatment with versus GLY (Chi-square or Fisher's exact test)
Dizziness	4	14.81	4	16.00	8	15.38
Nausea	4	14.81	4	16.00	8	15.38
Asthenia	2	7.40	2	8.00	4	7.69
Vomit	2	7.40	2	8.00	3	5.76
Facial paresthesia	2	7.40	0	0.00	2	3.84
Sweating	1	3.70	1	4.00	2	3.84
Cold extremities	1	3.70	1	4.00	2	3.84
Blurred vision	1	3.70	0	0.00	1	1.92
Headache	1	3.70	0	0.00	1	1.92
Constipation	1	3.70	0	0.00	1	1.92
Colic	1	3.70	0	0.00	1	1.92
Burning in thorax	1	3.70	0	0.00	1	1.92
Diarrhea	0	0.00	1	4.00	1	1.92
Fever	0	0.00	1	4.00	1	1.92
Paresthesia of members	0	0.00	1	4.00	1	1.92
Dyspnea	0	0.00	1	4.00	1	192
Serious adverse event ^d c,d P > 0.05 comparing treatment with versus GLY (Chi-square or Fisher's exact test)
Death ^e e Clinical feature of disseminated histoplasmosis	1	3.70	0	0.00	1	1.92
Head injury ^f f Motorcycle accident	0	0.00	1	4.00	1	1.92

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