Everyone experiences constipation sooner or later. Difficulties with bowel movements cause a lot of troubles, anxiety, and deterioration in well-being. To eliminate this problem, you can use medications and traditional medicine. Laxatives, the main active ingredient in which is lactulose, are very popular. They are in demand because they have a number of advantages:
- safety;
- soft impact;
- efficiency;
- a minimum set of unpleasant side effects.
In addition, the body does not get used to drugs of this group, so there is no need to fear that intestinal motor functions will decrease.
Description:
Transparent viscous liquid from colorless to yellow with a brownish tint.
Pharmacotherapeutic group:
laxative.
ATX code:
A06AD11.
Pharmacological properties
Pharmacodynamics
It has a hyperosmotic laxative effect, stimulates intestinal motility, improves the absorption of phosphates and calcium salts, and promotes the excretion of ammonium ions.
Lactulose is broken down by the intestinal flora of the colon into low molecular weight organic acids, which leads to a decrease in pH and an increase in osmotic pressure and, as a result, an increase in the volume of intestinal contents. These effects stimulate intestinal motility and affect stool consistency. The physiological rhythm of emptying the large intestine is restored.
In hepatic encephalopathy and hepatic (pre)coma, the effect is due to the suppression of proteolytic bacteria by increasing the number of acidophilic bacteria (for example, lactobacilli); the transition of ammonia into ionic form due to acidification of the contents of the colon; bowel movements due to a decrease in pH in the colon and the osmotic effect; as well as reducing nitrogen-containing toxic substances by stimulating bacteria that utilize ammonia for bacterial protein synthesis.
Lactulose as a prebiotic substance enhances the growth of beneficial bacteria such as bifidobacteria and lactobacilli, which in turn helps to suppress the growth of potentially pathogenic bacteria such as Clostridium and E.coli, and provides a more favorable balance of intestinal flora.
Has the ability to inhibit the growth and reproduction of salmonella and shigella. Does not reduce the absorption of vitamins and is not addictive.
The effect occurs 24-48 hours after administration (the delay is due to the passage of the drug through the gastrointestinal tract).
Pharmacokinetics
Absorption is low (renal excretion is 3%). Without being absorbed, it reaches the large intestine, where it is broken down by intestinal flora. Completely metabolized at doses of 40-75 ml; at higher dosages, it is partially excreted unchanged through the intestines.
Lactulose for children
The fact that lactulose can be beneficial for children was established by pediatricians in Austria back in the late 1940s. Observing bottle-fed babies, we noticed that dysbacteriosis occurs in such babies several times more often than in babies fed breast milk. After a series of experiments, it turned out that human milk contains lactulose, and this, in turn, provides healthy intestinal microflora.
Chemists have learned to synthesize this substance from lactose. And pharmacists introduce it into syrups that improve the microflora of children's intestines. This syrup can be given to children of all ages. The instructions for use describe in detail the dosages for each age group.
For adults, lactulose is available in the form of dietary supplements, laxative tablets, and other pharmaceutical forms. At the same time, the effect on the body is the same.
Directions for use and doses
The drug is intended for oral administration,
during or after meals.
Lactulose may be given as a single daily dose, or the dose may be divided into two doses using a measuring cup.
All dosages must be selected individually. If one dose is prescribed per day, it should be taken at the same time, for example, during breakfast.
For constipation:
- children under 1 year: 5 ml/day;
- children from 1 to 6 years: 5-10 ml/day;
- children from 7 to 14 years: 15 ml/day;
- children over 14 years of age and adults: in the first three days, 15-45 ml/day, then 10-30 ml/day.
The laxative effect of the drug develops during the first two days of administration. The duration of treatment is from 4 weeks to 3-4 months.
With hepatic coma, (pre)coma, encephalopathy
:
The initial dose is 30-45 ml 3 times a day. Then the dose is selected so that soft stools are produced 2-3 times a day. Treatment can last up to 3 months or more.
For hepatic coma, (pre)coma and hepatic encephalopathy: 30-50 ml orally 3 times a day, the daily dose can be 90-190 ml; then in an individually selected maintenance dose (providing a stool pH of 5-5.5) 2-3 times a day.
In the postoperative period
:
Adults: 10-30 ml 3 times a day, children over 1 year: 5-10 ml 2-3 times a day, up to 1 year: 5 ml 2-3 times a day. The drug is prescribed 18-24 hours after surgery for 3-5 days.
Food sources
The list of foods rich in lactulose does not only include dairy products. Although, of course, there are more substances in this category. So, to enrich the body with a useful prebiotic, it is important to pay attention to breast milk, natural yoghurts, cottage cheese, bananas and rye bran. Cauliflower, broccoli, asparagus, corn, beans and even onions or garlic can be used as sources of this beneficial substance. Sweet lovers can replenish their prebiotic reserves from dried apricots and black currants.
Side effect
Side effects are usually mild and reversible and are a consequence of exceeding the dose.
In the first days of taking lactulose, flatulence may occur, which, as a rule, disappears after 1-2 days. If high doses are used for a long time in the treatment of hepatic encephalopathy, the patient may develop electrolyte imbalances as a result of diarrhea and, as a result, convulsions, flatulence, nausea, headache, dizziness, arrhythmia, myalgia, increased fatigue, and weakness.
Deficiency Symptoms
You can understand that the body does not have enough lactulose by looking at several of the most common symptoms. The most common and most important symptom is regular constipation, and to eliminate the problem it is enough to treat the body with a prebiotic for several days. Other symptoms of dysbiosis (which is most often a consequence of lactulose deficiency) may include:
- nausea;
- vomiting;
- weight loss;
- stomach ache.
Well, in total, all these disorders lead to disruption of metabolic processes and the function of the digestive organs.
special instructions
If there is no therapeutic effect within two days or if constipation returns after treatment, the patient is advised to consult a doctor.
The drug should be administered with caution to patients with galactose intolerance. Please note that the drug may contain small amounts of bound sugars (for example, lactose, galactose, epilactose).
When treating hepatic (pre)coma, higher doses of the drug are usually prescribed, which should be taken into account in patients with diabetes mellitus.
When treating children, laxatives should be used in exceptional cases and under medical supervision. It must be taken into account that during treatment, disorders of the emptying reflex may occur.
Patients with rare congenital disorders such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use this drug.
With long-term use of the drug (more than 6 months), the concentration of potassium, chlorine and carbon dioxide in the blood plasma should be regularly monitored.
For gastrocardial syndrome, doses should be increased gradually to avoid flatulence.
What determines the level of lactulose in the body?
Lactulose belongs to substances that the body is unable to synthesize on its own. Therefore, the only source of prebiotics for humans is food and bioactive supplements. If we are not talking about the treatment of advanced chronic diseases, then to maintain a stable level of lactulose, a balanced, proper diet, with the consumption of foods rich in microelements, vitamins and other beneficial substances, is sufficient. In more complex cases, medications containing high concentrations of lactulose come to the rescue. But you shouldn't be afraid of these drugs. They cause virtually no side effects and are allowed even for infants.
Lactulose for weight loss
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Perhaps half of overweight people dream of a miracle diet that will help them lose 5 or even 10 extra pounds in a week. Nutritionists, hearing this, say: “Nonsense! This cannot be! But advertising promises something else. Most drugs that quickly get rid of excess weight work on the principle of a laxative. For this reason, lactulose is sometimes also used inappropriately. By consuming drugs based on this substance, obese people want to achieve a laxative effect to reduce weight.
But a laxative, even the strongest one, has no effect on fat deposits. And false weight loss occurs only due to loss of moisture. Continuing this “weight loss” for several days, the only result that can be achieved for sure is dehydration and leaching of nutrients from the body. And even the beneficial properties of lactulose will not save the situation.
But there are options when lactulose can be taken for weight loss, or more precisely, as an adjuvant. When following a diet, especially if there are few foods rich in fiber in the diet, constipation often occurs. This is where lactulose comes to the rescue - it will help quickly remove waste products from the body, cleanse the intestines and take care of the correct microflora. As a result, this will affect your overall well-being, increase your tone and strengthen your immune system. This means you will have the strength to exercise, without which there will definitely be no effective weight loss.
Lactulose: arguments and facts
Lactulose (4-O-beta-D-galactopyranosyl-D-fructose) is a synthetic disaccharide consisting of residues of galactose and fructose molecules. Lactulose is a stereoisomer of lactose. Medicines based on lactulose are available in the form of syrup or tablets. Indications for the use of lactulose preparations include: treatment of acute or chronic constipation, the need to achieve a soft stool consistency (in case of painful processes, the need for surgical intervention in the colon and/or anal area, in the postoperative period); treatment and prevention of hepatic encephalopathy; hyperammonemia of various origins. Lactulose is also used in the hydrogen breath test to detect bacterial overgrowth in the small intestine and assess motility. An extensive series of works by domestic and foreign authors is devoted to the study of the effect and tolerability of lactulose in various diseases. Among them, a prominent place is occupied by studies of the drug Normaze (lactulose syrup, Dr. Reddy's), which is widely used in Russia.
Lactulose in the treatment of constipation
One of the most important areas of application of lactulose is the treatment of acute and chronic constipation of various etiologies in patients of all age categories, including newborns and elderly patients. Lactulose can be prescribed as monotherapy, as well as in conjunction with laxatives based on dietary fiber, polyethylene glycol, and simultaneously with short courses of stimulant laxatives.
In adults, for the treatment of constipation, an initial dose of lactulose of 15–30 ml at night (if taken systematically in the morning) is recommended, with subsequent modification based on the frequency and consistency of stool [1].
According to surveys and analysis of medical records, approximately a quarter of the population of developed countries suffers from chronic constipation. A significant proportion of cases are primary, or idiopathic, constipation associated with poor lifestyle or functional disorders [2]. In the treatment of constipation, non-drug methods are not effective in all patients; there is a need to prescribe laxatives [2].
A systematic review by D. Ramkumar and SS Rao (2003) and a review by J. Johanson (2007) analyzed randomized trials (over the period 1966–2006) that assessed the effectiveness and safety of various laxatives in the treatment of chronic constipation in adults. The most convincing efficacy data corresponding to levels of recommendations A and B are obtained for polyethylene glycol (PEG), lactulose, psyllium and tegaserod [2, 3].
A systematic review of drugs for the treatment of constipation in adults recommended by the FDA (Food and Drug Administration) emphasizes that, despite some methodological shortcomings of the clinical studies conducted, the effectiveness of lactulose is beyond doubt (recommendation level B), although it is slightly inferior in severity of action PEG and dietary fiber preparations in combination with senna preparations [4].
Experts - authors of recommendations for the treatment of chronic constipation - believe that for irritable bowel syndrome with constipation, lactulose is most effective in cases where abdominal pain is significantly reduced after defecation. Due to the insufficient amount of research on the safety of lactulose in irritable bowel syndrome with constipation, it is more advisable to prescribe a disaccharide as an alternative to PEG - if the latter is ineffective or intolerable [1].
Lactulose is effective in the treatment of constipation, which develops when the urge to defecate is often ignored (in children and adults), since with systematic use of the disaccharide, a distinct and persistent urge is formed. Treatment begins with a low dose, with a gradual increase over several weeks until the effect is achieved, when the patient cannot ignore the urge to defecate. The effect lasts for several weeks and even months after discontinuation of the drug.
Dietary fiber and lactulose exhibit prebiotic properties and serve as sources of short-chain fatty acid (SCFA) production in the colon. The similarity and “naturalness” of the action of laxatives of these two classes served as the basis for organizing comparative studies.
A randomized, open-label, parallel group study of 124 patients with chronic idiopathic constipation compared the effectiveness of psyllium and lactulose. The duration of treatment was 4 weeks. Both laxatives showed similar positive effects on stool frequency, consistency, and general symptoms; were equally effective in reducing abdominal pain and the need to strain. Patients noted a more pleasant taste of lactulose [5].
A study of similar design and duration by N. Quah et al. was designed as a crossover study with a minimum washout period of 1 week. The number of participants was 50. The authors of the publication emphasize a more distinct and predictable effect of lactulose: with its use, the average frequency of stools was 7.3 times per week (95% CI (confidence interval): 5.7–8.9), whereas with taking dietary fiber – 5.5 times a week (95% CI: 4.4–6.5); p = 0.001. The consistency of stool on a conventional scale was 3.4 (95% CI: 3.1–3.7) and 2.9 (95% CI: 2.5–3.3) points, respectively; p = 0.018. A scale for assessing difficulty with defecation showed similar results. There were no significant differences in drug tolerability, although adverse events were recorded somewhat more frequently when taking lactulose. The final scale for assessing the effectiveness of patients when treated with lactulose was 6.2 points (95% CI: 5.5–7.0), when treated with dietary fiber – 4.8 (95% CI: 4.0–5.9); p = 0.017. Of the 39 patients who completed the study, 24 (61.5%) preferred lactulose, 14 (35.9%) preferred dietary fiber [6].
French researchers compared different regimens of lactulose for chronic idiopathic constipation: 20 g per day in one or two doses. The study was designed as a multicenter, double-blind, crossover design (2 dosing regimens, 3 weeks each). The total number of participants was 121. The results showed that the number of bowel movements per week (7.29 ± 3.20 vs. 7.08 ± 3.03), stool consistency, ease of defecation, frequency and severity of side effects were not significantly different [7 ].
A serious problem is the high prevalence of constipation in elderly and senile patients and its features - frequent slowing of intestinal transit, weakening of the pelvic floor muscles, decreased sensitivity of the rectum, and a tendency to irritate the mucous membrane with dense feces. The use of some laxatives in the elderly carries a high risk of complications - fecal impaction (when prescribing dietary fiber), water and electrolyte disorders (when prescribing salts and careless use of stimulants). Today, researchers are unanimous that in the elderly and senile age, bulk and osmotic laxatives - polyethylene glycol and lactulose - are most suitable as the main means of treating chronic constipation. Lactulose preparations do not irritate the colon mucosa and are not addictive; the active substance and metabolites do not enter the systemic circulation. Stimulant laxatives - senna preparations, bisacodyl, sodium picosulfate - are prescribed in short courses when osmotic agents are insufficiently effective or for occasional constipation [8, 9, 10].
Lactulose has been successfully used to treat symptomatic constipation.
The administration of lactulose (Normaze) in the early period after colon surgery significantly improves treatment results compared to the group of patients taking petroleum jelly. In particular, the duration of postoperative ileus is significantly reduced [11].
For constipation during treatment with opioid analgesics, the use of lactulose or PEG preparations has shown its effectiveness and safety [12, 1].
Lactulose in the form of monotherapy has an effect in some cases of laxative abuse.
Unlike the vast majority of other laxatives, lactulose is approved for use in pregnant and lactating women. Up to 66% of pregnant women note such manifestations of constipation as rare stools, dense stool consistency, and the need for additional straining. The reasons for this are the influence of progesterone on the excitability of intestinal smooth muscle cells, a sedentary lifestyle, taking iron supplements, compression of the intestines by the uterus, etc. Untimely bowel movements can have an adverse effect on the course of pregnancy. In the postpartum period, the cause of bowel dysfunction is changes in the sensitivity and strength of the pelvic floor muscles. The FDA classifies lactulose as a pregnancy risk category B drug. Lactulose does not have embryotoxic or teratogenic effects; in adequate doses does not cause a pronounced increase in intestinal motility and fluid loss, which could have a negative effect on uterine tone and placental blood flow [13]. Lactulose does not enter the systemic circulation and is not found in breast milk.
In the study by T.N. Sokur et al. studied the effectiveness and tolerability of lactulose (Normaze) in women at different stages of pregnancy who suffered from constipation resistant to non-drug treatment methods. The total number of participants was 150. The recommended dose of Normaze was 20–45 ml per day and was selected individually; Duration of treatment: 7–28 days. As a result of treatment, 145 (96.7%) pregnant women had normal stools, a feeling of complete bowel movement, and in 98 (65.3%) the feeling of heaviness and pain in the hypochondrium decreased. Normalization of intestinal function contributed to an improvement in overall well-being. Side effects such as nausea, flatulence, abdominal pain, loose stools with tenesmus were recorded in isolated cases, were moderate and did not require discontinuation of the drug. In no case was there any emergence or worsening of signs of threatened miscarriage, deterioration in general health, or an increase in the severity of preeclampsia [13].
A multicenter, open-label, controlled study of the efficacy and tolerability of lactulose in pregnant women with chronic or episodic constipation (n = 62) was conducted in Switzerland: in 34% of patients, constipation existed before pregnancy, and in the rest it was regarded as “constipation of pregnancy.” Lactulose was prescribed for 4 weeks. Stool frequency increased after a week and reached an optimum (6 times per week) after 2 weeks of treatment; The consistency of stool was normalized. “Good” and “very good” overall assessment of the effect of lactulose was given by 84% of attending physicians and 81% of patients [14].
Lactulose can be recommended for widespread use in rheumatological practice. In patients receiving NSAIDs and cytotoxic drugs, chronic constipation is often associated with hemorrhoids, anal fissures, complicated by dangerous bleeding or infection. It is preferable for such patients to be prescribed laxatives that do not have an irritating effect on the intestinal mucosa.
In the work of A.E. Karateev studied the tolerability of lactulose (Normaze) in patients with rheumatic diseases and chronic constipation. The study included 50 patients. The initial dose of lactulose was 30 ml at night, with subsequent adjustment - 15–60 ml per day; Duration of treatment – 2 weeks. In two patients, lactulose was discontinued due to undesirable effects (increased hemorrhoidal bleeding, severe flatulence). Normalization of stool was achieved in a quarter, significant improvement in 19 (39.6%) patients. The general well-being of patients improved [15].
It should be noted that in randomized studies of the effectiveness and safety of lactulose for chronic constipation in adults (including the elderly), the maximum duration of treatment was 12 weeks [16, 17]. New studies are needed on the safety of the drug with longer use. According to the instructions for lactulose preparations, when taking it for 6 months or longer, it is necessary to control the content of potassium, chlorides and carbon dioxide in the plasma, since long-term diarrhea can lead to disturbances in water and electrolyte balance.
In children, constipation often leads to the development of encopresis - fecal incontinence, inability to control bowel movements, and is also very often combined with delayed gastric emptying and pathological gastroesophageal reflux [18].
Many studies have been devoted to assessing the effect of lactulose in acute or chronic constipation in children, both in Russia and abroad. However, the lack of large randomized trials currently does not allow for a meta-analysis and the development of strict recommendations on dosage and duration of treatment [19].
In the study by L.N. Tsvetkova et al. 135 children aged from 1 to 15 years with constipation duration from 1 week to 4 months participated. The majority were patients aged 1 to 3 years. Triggering factors in the development of acute constipation were the prescription of medications, intestinal infections, changes in habitual lifestyle, etc. Children 1–6 years old were prescribed lactulose (Normaze) 5–10 ml 2–3 times a day, over 6 years old – 10–15 ml 2-3 times a day until stable regular bowel movements are achieved. In 121 children (89.6%) a positive effect was obtained within 7–12 days from the start of therapy; at the same time, abdominal pain and other complaints associated with constipation resolved; in a significant proportion of cases, normalization of the microbial composition of the microflora of feces was noted [20]. The use of lactulose and normalization of stool in children are accompanied by positive dynamics in the manifestations of reflux disease, reducing the frequency of its relapses and the development of severe complications [18].
Experiments with manometry have shown that after oral or rectal administration of lactulose, a decrease in gastric tone is observed and its ability to stretch increases; this effect appears to be of a reflex nature [21].
Lactulose in the treatment and prevention of hepatic encephalopathy
Another important area of application of lactulose is the treatment and prevention of hepatic encephalopathy (HE).
The therapeutic mechanism of action of the drug is not limited to the ability to increase the excretion of ammonia by changing the intestinal pH and laxative effect. In all likelihood, the prebiotic potential of lactulose is also important: by maintaining the mass of saccharolytic bacteria, the ammonium-producing population of intestinal microorganisms is suppressed. Some probiotics also exhibit these mechanisms of action, although evidence is currently insufficient [22, 23]. According to modern concepts, the development of PE is associated with impaired permeability of the intestinal barrier, changes in intestinal microbiocenosis and secondary inflammation. Liver cirrhosis, especially complicated by PE, is accompanied by significant changes in fecal microflora. The quantitative content of some of them (families Alcaligeneceae, Porphyromonadaceae, Enterobacteriaceae) in feces is associated with the severity of brain dysfunction and signs of inflammation [24].
In the intestine, ammonia is formed primarily as a result of bacterial deamination of amino acids. The use of antibiotics as first line of therapy can lead to the selection of resistant strains of ammonium-producing bacteria, and their use is not always justified. Non-absorbable disaccharides - lactulose, lactitol - as a result of laxative action and gas formation, cause rapid evacuation of bacteria and ammonia [25].
The effect of lactulose in the treatment of clinically manifest stages of PE has been shown in numerous works by domestic and foreign authors; lactulose has earned a reputation as an effective and reliable agent in the management of such patients. However, it should be noted that there is a lack of well-designed controlled studies on this issue.
In 2004, the Cochrane Hepato-Biliary Group published a systematic review regarding the effects of non-absorbable disaccharides (lactulose and lactitol) in hepatic encephalopathy. The analysis included 30 randomized trials that compared the effectiveness of lactulose and the natural disaccharide lactitol, placebo, antibiotics, and no intervention. The analysis showed that, compared with placebo or no intervention, administration of nonabsorbable disaccharides had no significant effect on mortality (OR death (RR) 0.41; 95% CI: 0.02–8.68). The results may have been influenced by methodological shortcomings of the studies. Disaccharides significantly contributed to reducing the severity of HE (OR no improvement 0.62; 95% CI: 0.46–0.84). The authors concluded that there is insufficient high-quality research evidence to definitively confirm the effectiveness of disaccharides in the treatment of PE [26].
Despite such uncertain data from a meta-analysis (2004), lactulose is included in modern recommendations for the treatment of type C HE (developing against the background of liver cirrhosis), in which hyperammonemia has an undoubted pathogenetic significance. Treatment of acute hepatic encephalopathy due to cirrhosis of the liver includes, among other things, the administration of lactulose in enemas (300 ml of syrup in 700 ml of water, trying to fill the entire colon) or through a naso-gastric tube (in case of deep encephalopathy). For oral administration, an initial dose of 45 ml and dose titration hourly until stool appears (usually 15–45 ml over 6–12 hours) are recommended; it is possible to replace lactulose with a non-absorbable antibiotic (neomycin, rifaximin).
In chronic encephalopathy against the background of liver cirrhosis (in the pathogenesis of which, apparently, hyperammonemia is even more important), the dose of lactulose is selected in such a way as to achieve 2-3 bowel movements per day and a soft stool consistency. Usually, 15–30 ml of syrup is first prescribed 2 times a day, then they switch to an individually selected regimen. Antibiotics are classified as reserve drugs in cases where the effect of lactulose is insufficient or it is poorly tolerated. A combination of lactulose, antibiotics, and zinc preparations is possible [27, 28, 29].
In recent years, close attention has been paid to the problem of so-called “minimally expressed” hepatic encephalopathy, in which brain dysfunction is detected only with special neuropsychological testing and instrumental studies. This form carries an increased risk of developing manifest PE, reduces the reaction rate, and can limit the patient’s daily activity.
M. Luo et al. published a meta-analysis of 9 studies (total number of participants 434) that examined the effect of lactulose in minimally severe PE. According to neuropsychological testing, lactulose significantly improved reaction time and attention (OR no improvement 0.52; 95% CI: 0.44–0.62; p
The effect of lactulose on intestinal microbiocenosis
Lactulose exhibits prebiotic properties, stimulating the growth of bifidobacteria and some lactobacilli. An increase in the biomass of saccharolytic bacteria appears to potentiate the laxative effect.
Unlike many probiotics, the therapeutic and preventive effect of lactulose is not reduced by antibiotic therapy.
A placebo-controlled study by J. Ballongue et al was devoted to studying the effect of lactulose and lactitol at a dose of 20 g per day on the growth of microorganisms in the colon in 36 healthy volunteers. With the use of both prebiotics, an increase in the mass of saccharolytic bacteria, a decrease in the activity of procarcinogenic enzymes and ureases in feces, an increase in the total content of SCFA, a slight decrease in pH and an increase in water content in feces were noted [32].
In the work of O.N. Minushkina et al. It has been shown that in case of duodenal ulcer, the administration of standard triple anti-Helicobacter therapy for 12 days in combination with lactulose (Normaze) is accompanied by improved tolerability of treatment. The frequency of bloating, the development of diarrhea and the identification of signs of disturbances in the composition of the intestinal microflora are reduced. The latter was assessed based on the study of the absolute concentration of SCFAs (C2–C6) and their profiles, as well as the values of anaerobic indices and the total relative content of isoacids in feces. The authors note that initially there was a decrease in the content of acetic acid in the patients’ stool, which may be explained by a decrease in the activity of obligate saccharolytic intestinal microflora. At the same time, the examined groups of patients were characterized by a SCFA profile indicating an increase in the activity of bacteroides, clostridia, eubacteria, fusobacteria, and coprococci [33].
Some studies have shown the ability of lactulose to suppress the growth of Salmonella, Shigella, Clostridia, Proteus, Klebsiella and Candida fungi, probably by reducing the pH of the environment and stimulating the growth of saccharolytic bacteria [34]. The experiment showed that if the number of viable pathogenic bacteria in the presence of ciprofloxacin decreased by approximately 100 times, then when ciprofloxacin was co-administered with lactulose, it decreased by 1000 times. In addition, a positive effect of lactulose on the spreading ability of neutrophils and mononuclear phagocytes has been established [35]. Lactulose (Normaze) is recommended to be prescribed during the period of early convalescence, with an emerging resolution of diarrhea and a decrease in symptoms of intoxication.
Y. Bouhnik et al. compared the effect of two osmotic laxatives - lactulose and polyethylene glycol - on the intestinal microbiocenosis in the treatment of chronic idiopathic constipation. The composition of fecal microflora was assessed. A multicenter, parallel-group, randomized controlled trial included 65 patients with idiopathic constipation. Patients received powdered lactulose or PEG-4000. In the first week the dose was fixed (20 g at night), during the next 3 weeks the dose could be adjusted based on the assessment of effect and tolerability (10–30 g/day). Bacteriological analysis of stool was carried out one day before the start of therapy and on the 21st and 28th days of treatment. The effectiveness and tolerability of laxatives was similar in both groups. In the group receiving lactulose, there was an increase in the population of bifidobacteria (p = 0.04), lactase activity (p
Considering the effectiveness of lactulose as a prebiotic and the high safety of its use, some authors recommend prescribing it not only for intestinal infections (in particular, salmonellosis), but also for patients with hemoblastosis during high-dose polychemotherapy [37].
Lactulose has been proposed to be used for sanitization of the birth canal (prevention of candidiasis and intrauterine infection of the fetus), prescribed 2–3 weeks before birth [38].
In their review article, S. Macfarlane et al. emphasize: despite the small number of randomized controlled studies assessing the probiotic effect of lactulose, oligofructose and galactooligosaccharides, promising results from animal experiments have been obtained, indicating that these substances have a distinct anti-inflammatory effect in the intestine and significantly improve calcium absorption. Perhaps in the future they will find application in the treatment of inflammatory bowel diseases and calcium metabolism disorders [39].
Domestic pediatricians recommend the use of lactulose in order to normalize intestinal functions in formula-fed children of the first year of life and in premature infants in the first month of life with various concomitant pathologies [40, 41].
Various aspects of the therapeutic and preventive effects of lactulose in the treatment of constipation, liver and intestinal diseases continue to be actively studied; The website www.clinicaltrials.gov lists numerous clinical trials currently underway. The continued interest in this drug underscores its relevance in various areas of clinical practice.
