Chemistry Reference
In-Depth Information
l-rhamnose (25 g), yields more propionate relate to acetate,
46
but longer-term stud-
ies have not shown reductions in serum lipids.
47
Lactulose, a rapidly fermented
dietary fiber, has been shown to increase colonic fermentation and serum cho-
lesterol compared to a control group that did not receive the intervention.
48
The
increase in cholesterol may be a result of increased production and absorption
of colonic acetate, which is a substrate for increased hepatic lipogenesis.
48
Other
substrates such as psyllium, which are viscous fiber sources, are less fermentable
and have been shown to be very effective in reducing serum lipids.
38,49
This effect
may be related to the increase in fecal losses of bile acids. These fermentable
substrates may also generate propionate,
37,38
which have been suggested to reduce
serum cholesterol levels by offsetting the hyperlipidemic effect of acetate genera-
tion. However, results from human studies have been inconsistent. Intakes of 2.7 g
of sodium propionate given in bread
50
and 7.5 g of sodium taken as capsule
51
did
not affect serum lipids. Only one study showed that 5.4 g of propionate given daily
for 2 weeks decreased total cholesterol and low-density lipoprotein cholesterol
(LDL-C) in subjects with total cholesterol > 5.5 mmol/L.
52
In healthy young men
and women, rectal infusions of propionate (180 mmol) did not affect serum lipids
or triglycerides.
53
However, when propionate (60 mmol) was infused with acetate
(180 mmol), free fatty acids decreased by an additional 10 percent and negated
the increase in total and LDL-C seen when acetate was given alone.
53
Therefore,
it appears that the ratio of propionate to acetate may be one of the mechanisms of
action by which propionate reduces serum lipids.
53-56
11.5 ProPIoNATE
Propionate is produced through two main pathways: (1) fixation of CO
2
to form
succinate, which is subsequently decarboxylated (the “dicarboxylic acid pathway”);
and (2) from lactate and acrylate (the “acrylate pathway”).
26
Propionate is a sub-
strate for hepatic gluconeogenesis and has been associated with the inhibition of
cholesterol synthesis in hepatic tissue.
51
However, propionate appears to have two
competing and opposing effects on gluconeogenesis. It is both a substrate for gluco-
neogenesis and an inhibitor of gluconeogenesis. Propionate enters the Krebs cycle at
the level of succinyl CoA. The inhibition of gluconeogenesis by propionate may be
related to its metabolic intermediaries, methymalonyl CoA and succinyl CoA, which
are specific inhibitors of pyruvate carboxylase.
57
Propionate enhances glycolysis,
possibly by depleting hepatic citrate,
58
which is an important metabolic inhibitor of
phosphofructokinase. Propionate may also have an indirect effect on hepatic glucose
metabolism by lower concentrations of plasma free fatty acids, which, in itself, is
known to be closely related to the actual rate of gluconeogenesis.
59
Much of the
knowledge about the nutritional fate of propionate comes from studies of ruminants.
Due to the presence of microbiota in the rumen of ruminants, which digest and
ferment carbohydrates, intestinal glucose update is minimal. Therefore, the produc-
tion of SCFA constitutes the major source of ruminant energy,
60
where propionate is
