Chemistry Reference
In-Depth Information
In the colon, bacteria metabolize it into hydrogen, methane, and carbon dioxide,
mainly lactic acid and acetic acid, lowering the pH, especially in the cecum.
9,10
In
vitro
some propionate and butyrate are also produced.
3
In the naïve subject, large
amounts of undigested lactulose induce symptoms of cramps, gas, bloating, and
diarrhea.
7,9
The mechanism is thought to be largely due to osmotic forces increas-
ing small intestinal volume and transit with resultant high flow across the ileocecal
valve and possibly overwhelming the reserve capacity of the colon. It has also been
shown that small amounts (10 to 15 g twice a day) may induce tonic contractions of
the colon leading to the known anticonstipating effect.
11,12
This compound shares with lactose the ability to auto adapt to continued inges-
tion.
13,14
The definition of colonic adaptation refers to reduction of measured exhaled
breath hydrogen, improvement of the outlined symptoms, and a statistically signifi-
cant increase in measured fecal β-galactosidase.
14
In human volunteers, adaptation
is achieved by consuming 20 g of lactulose twice daily for 8 days.
Lactulose is unusual among prebiotics because it has been in medicinal use since
the 1950s, predating the labeling and definition of the food additive by Gibson and
Roberfroid.
15
Although it was recognized early that many of the effects of lactulose
may work through its influence on microflora, especially bifidobacteria,7
7
historically
it was sold and prescribed as a drug. As such, it still requires a doctor's prescription
in most countries. However, by the late twentieth century, lactulose was available as
a food additive in Italy, Japan, and the Netherlands.
7
Lactulose, therefore, is the first true prebiotic recognized for its effects on the
gut flora. The effects of the sugar may be divided into physiological and those
related to selective promotion of specific gut bacteria. However, it is difficult
to separate these two effects, with few exceptions, because as more is learned
about host/bacterial communications, the more putative medicinal and bacterial
effects merge.
A marked effect on bifidobacteria of this substance has been shown in numer-
ous human trials.
7
Addition of lactulose to bottle-fed infants raised bifidobacteria
levels to that found in breastfed infants.
16
Large daily dose intake of 20 to 60 g
17,18
or
small amounts of 5 g twice a day for 6 weeks
19
both induce bifidobacteria in human
volunteers. The magnitude of bifidogenic effect is influenced by the initial bacterial
counts. The lower the initial levels, the higher the postconsumption expansion.
20
In
addition to total bifidobacteria, the species
Bifidobacterium adolescentis
is specifi-
cally increased after 18 weeks of lactulose ingestion in healthy volunteers.
21
The effects of lactulose also result in the decrease of a number of enzymes
including β-glucuronidase,
17,22
an enzyme considered pathogenically relevant to col-
orectal carcinogenesis.
23,24
Furthermore, lactulose reduces colonic fermentation of
amino acids in human volunteers.
25
Reduction of bacterial proteolysis is considered
therapeutic for hepatic encephalopathy (see below) and possibly beneficial for some
intestinal diseases. The same study also revealed that over a 4-week course, intestinal
permeability decreased, but gastric emptying and oral cecal transit were unaffected.
25
Other postulated effects are discussed in the context of specific medical use.
