Chemistry Reference
In-Depth Information
the primary precursor for gluconeogenesis. However, in humans, the metabolism of
propionate is less well understood.
Propionate may also have systemic effects in humans, including a potential hypo-
lipidemic action. Results from animal studies suggest that propionate inhibits cho-
lesterol synthesis by inhibiting both 3-hydroxy-3-methylglutaryl-CoA synthase and
3-hydroxy-3-methylglutaryl-CoA reductase.
61,62
As mentioned earlier, polyfructans
are bifidogenic and may improve the acetate:propionate ratio, which is associated
with a reduction in serum lipids. The use of polyfructans (e.g., Neosugar, inulin) in
individuals with type 2 diabetes mellitus (8 g/day)
63
and hyperlipidemia (18 g/day)
64
resulted in decreases in serum cholesterol. However, no hypolipidemic effect (20
g/day) was observed in healthy subjects.
65
Other studies have also investigated the
effect of polyfructans on blood lipids in the dose range of 8 to 20 g/day, but have
yielded inconsistent results.
66
This inconsistency in human intervention studies, in
contrast to animal experiments, may be related to species differences. Numerous
mechanisms have been proposed to be responsible for the observed lipid-lowering
effect, with increased production of propionate being one of the possible mecha-
nisms of action. Increased production of propionate, through fermentation, may
inhibit hepatic cholesterol synthesis.
39,54,61,67-69
This effect has been supported in
studies with hyperlipidemic experimental animals,
38,39
but not supported in other
animal studies.
70-72
To date, there are limited experimental studies in humans that
have quantified the production of acetate and propionate specifically related with the
use of prebiotics. Absorption of propionate from the human colon is more efficient
than acetate,
73,74
and studies in ruminant mucosa show that propionate is activated to
its CoA derivative (a step required for its oxidation) to a greater extent than acetate.
75
During a single pass, the liver extracts 90 percent of propionate, as opposed to 75
percent of acetate
76,77
and colon infusions of equal amounts of acetate and propionate
suggest that the amount of colonic propionate reaching peripheral blood is only 25
percent of the amount of colonic acetate doing so.
53
11.6 buTyrATE
Butyrate is an important SCFA not only as the preferred fuel of the colonic epi-
thelial cells, but it also plays a major role in the regulation of cell proliferation and
differentiation and may be beneficial for inflammatory bowel disease.
1,25,78,79
It is
estimated that 70 to 90 percent of butyrate is metabolized by the colonocyte, thus
making it the most important SCFA in colonocyte metabolism.
2
Butyrate is used
preferentially over propionate and acetate in a ratio of 90:30:50,
2
and is preferred
over glucose or glutamine supplied by blood.
80
More than 70 percent of the oxygen
consumed by human colonic tissue is due to butyrate oxidation. Sodium butyrate
exerts an antiproliferative effect on many cell types, and evidence from animal and
cell line studies suggests that it also has preventive effects on colon cancer and ade-
noma development.
81
Similar effects have been shown with acetate and propionate
where apoptosis was induced in colorectal tumor cell lines, but to a much lesser
extent than butyrate.
82,83
Butyrate also stimulates immunogenicity of cancer cells.
84
