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To the Editor:

We read with interest the paper by Liu et al. recently published in HEPATOLOGY in which they demonstrated that oral coadministration of fermentable fiber and live bacteria significantly improved gut flora, plasma ammonia levels, neuropsychological tests, endotoxemia, and the Child-Turcotte-Pugh score in patients with liver cirrhosis.1 They also demonstrated that fermentable fiber alone has similar therapeutic benefit. They assessed the effect of fermentable fiber by quantitative bacteriological and pH analysis of fecal samples.1 We have also undertaken a similar study but evaluated the effect by measuring plasma ammonia, serum short-chain fatty acid (SCFA) levels, and serum diamine oxidase (DAO) activity.2

In our study, 24 outpatients with viral cirrhosis were randomly assigned into 2 groups. A fermentable fiber product, Healsh Fiber (Ajinomoto Co., Ltd., Tokyo, Japan), containing 5 g of galactomannans per package was used. It was supplemented to food and given to 12 patients in the fiber group (7 men and 5 women; mean age, 60 ± 6 years; Child-Turcotte-Pugh classification: 6 patients in Group A, 3 in Group B, and 3 in Group C) at 5 g ter in die for 30 days. The blood levels of albumin, cholinesterase, ammonia, prothrombin time, SCFA, and DAO were measured before and 30 days after treatment. To evaluate nutrition status, meals for 3 days were recorded, and the fiber and energy intakes were calculated. To use as controls, blood tests and diet recordings were performed in 12 patients with cirrhosis (6 men and 6 women; mean age, 65 ± 5 years; Child-Turcotte-Pugh classification: 7 patients in Group A, 2 in Group B, and 3 in Group C) without fiber intake. During the observation period, other medications were not changed. Informed consent was obtained from all patients, and the Ethics Committee of Mie University School of Medicine approved the investigation protocol. Serum SCFA levels and DAO activity were measured by high-performance liquid chromatography and high sensitivity colorimetric methods.3–5 The sum of acetic acids, propionic acid and n-butyric acids levels was regarded as the level of SCFA. The background and changes in test results between the 2 groups were compared by using Mann-Whitney U test and Wilcoxon rank test, respectively. A P value less than .05 was considered as statistically significant.

There was no significant difference in patients' background and dietary intake at entry. High individual variability was observed in fiber intake, ranging from 7 to 21 g/d before the test. In the fiber group, ammonia levels significantly decreased from 49.5 ± 26.8 to 37.1 ± 19.8 μmol/L (P < .05), while SCFA levels and DAO activity significantly increased from 31.2 ± 9.8 and 11.1 ± 4.3 to 39.7 ± 6.9 μmol/L and 14.0 ± 5.0 U/L, respectively (both, P < .05). The results of other tests were not significantly changed. In the control group, neither blood test results nor nutritional element in food intake significantly changed during the observation period (Table 1).

Table 1. Changes in Blood Tests and Nutritional Element in Food Intake Before and After Fermentable Fiber Therapy
Blood TestsFiber GroupControl Group
At entryAfter 30 daysAt entryAfter 30 days
  • NOTE. Data are mean ± standard deviation.

  • Abbreviation: Ch-E, cholinesterase.

  • *

    P < .05 vs. data at entry.

Albumin (g/dL)3.4 ± 0.63.3 ± 0.63.1 ± 0.43.1 ± 0.4
Ch-E (ΔpH)0.48 ± 0.190.48 ± 0.20.4 ± 0.120.4 ± 0.13
Plasma ammonia (μmol/L, normal <40)49.5 ± 26.837.1 ± 19.8*43.8 ± 24.352.9 ± 20.9
Prothrombin time (%)73.7 ± 14.675.5 ± 15.270.7 ± 12.970.5 ± 14.9
SCFA (μmol/L, normal 60–100)31.2 ± 9.839.7 ± 6.9*24.3 ± 626.6 ± 8
DAO (U/L, normal 10–15)11.1 ± 4.314 ± 5*10.6 ± 3.210.1 ± 3.4
Nutritional Element in Food IntakeFiber GroupControl Group
At entryAfter 30 daysAt entryAfter 30 days
Energy (kcal)1618 ± 2031659 ± 2351857 ± 3191913 ± 261
Protein (g)58 ± 1263 ± 1358 ± 1664 ± 15
Fat (g)40 ± 1040 ± 734 ± 1039 ± 12
Carbohydrate (g)256 ± 32269 ± 51320 ± 51318 ± 40
Fiber (g)12 ± 526 ± 6*11 ± 411 ± 4

Fermentable fiber intake appears to change gut flora and increase SCFA, resulting in decreased plasma ammonia levels but increase in DAO activity. A decrease in pH with SCFA production in large intestine also appears to improve plasma ammonia levels.1 Fermentable fiber intake may be a supplementary treatment for patients with cirrhosis.

References

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  • 1
    Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. HEPATOLOGY 2004; 39: 14411449.
  • 2
    Rokkas T, Vaja S, Murphy GM, Dowling RH. Postheparin plasma diamine oxidase in health and intestinal disease. Gastroenterology 1990; 98: 14931501.
  • 3
    Nakao M, Ogura Y, Satake S, Ito I, Iguchi A, Takagi K, et al. Usefulness of soluble dietary fiber for the treatment of diarrhea during enteral nutrition in elderly patients. Nutrition 2002; 18: 3539.
  • 4
    Takagi K, Nakao M, Ogura Y, Nabeshima T, Kunii A. Sensitive colorimetric assay of serum diamine oxidase. Clin Chem Acta 1994; 226: 6775.
  • 5
    Hoshi S, Sakata T, Mikuni K, Hashimoto H, Kimura S. Galactosylsucrose and xylosylfructoside alter digestive tract size and concentrations of cecal organic acids in rats fed diets containing cholesterol and cholic acid. J Nutr 1994; 124: 5260.

Motoh Iwasa*, Makoto Nakao†, Yoshiaki Kato†, Yoshinao Kobayashi*, Kenji Takagi‡, Masahiko Kaito*, Yukihiko Adaci*, * Department of Internal Medicine Division of Gastroenterology and Hepatology Mie University School of Medicine Tsu, Japan, † Department of Pharmacy Mie University Hospital Tsu, Japan, ‡ Department of Medical Technology Nagoya University School of Health Sciences Nagoya, Japan.