Re: CR and cholesterol production

[Guest guest]

> CRers appear to stop endogenous production of cholesterol

> effectively.

Al,

I know of at least two CRers who have had elevated cholesterol levels.

The basic problem was that they consumed mostly MUFAs and almost no

PUFAs. PUFAs include linoleic acid (C18:2) which is an omega-6

essential fatty acid that has the highest cholesterol-reducing

properties.

CR may help to lower cholesterol during a weight loss phase, but once

you reach equilibrium at your target weight, the balance of fatty

acids (sat:mufa:pufa) and the ratio of carbohydrates-to-fat play a

significant role in maintaining good lipid levels. A major

complicating factor is that the fatty acids created from carbohydrates

(de novo synthesis of fatty acids) consists primarily of palmitic acid

which increases cholesterol. A compensating amount of linoleic acid

must be available in the diet since the omega-6 fatty acids cannot be

made by the body.

Tony

====

>

> CRers appear to stop endogenous production of cholesterol

effectively. It was

> interesting to present the results for Figure 2 comparing CR with

other means of

> blood cholesterol reduction in humans. It is food for not thought?

>

>

> PJ.

> Regulation of cholesterol biosynthesis by diet in humans.

> Am J Clin Nutr. 1997 Aug;66(2):438-46. Review.

> PMID: 9250128 http://tinyurl.com/mjwoy

>

> ... Dietary factors influencing human cholesterol synthesis

include energy

> restriction, meal frequency, dietary fat type, and cholesterol and

phytosterol

> content. Food deprivation for as short as 24 h results in almost

complete cessation

> of cholesterol biosynthesis. Similarly, increased meal frequency

patterns are

> associated with a substantial depression in synthesis. In contrast,

consumption of

> oils rich in polyunsaturated fatty acids, despite reducing circulating

> concentrations, increases the cholesterol synthesis rate compared

with other fats.

> Stepwise addition of dietary cholesterol is associated with only a

modest decline in

> cholesterogenesis while raising plasma concentrations slightly. It

can be concluded

> that synthesis, as a contributor to circulating cholesterol

concentrations, is

> sensitive to many dietary factors. Energy deprivation results in the

greatest

> decline in synthesis, likely accounting for the beneficial decline

in circulating

> cholesterol concentrations observed with weight loss.

> ... Food deprivation might be anticipated to exert two possible

actions on

> cholesterol synthesis. First, if dietary cholesterol was an

important control

> element, desuppression of cholesterogenesis would occur through

removal of incoming

> dietary input. Second, and in contrast, synthesis inhibition would

be expected if

> interruption of substrate supply for cholesterogenesis was an

important regulatory

> factor. Both animal and human literature bear out that any

desuppression due to

> absence of dietary cholesterol during food deprivation is minor

compared with the

> suppression caused by the removal of energy input itself. It has

been established

> that food restriction results in a marked reduction of

cholesterogenesis in animals

> (50, 54) and moderate suppression (59-61) to almost complete

suppression (43, 52) in

> human subjects. Although correlations between excess body weight and

synthesis rates

> have been identified (59, 60), suggesting that synthesis

reequilibrates to a new

> lower level with weight loss, it has also been shown that even very

acute energy

> restriction without weight loss exerts an immediate suppression of

synthesis (43,

> 61). Food restriction may result in a decrease in available

precursor for pathways

> of lipogenesis (50, 55). These observations provide an explanation

for the reduction

> in circulating cholesterol concentrations seen with weight loss in

humans in

> negative energy balance situations. Presumably, as with fatty acid

synthesis, an

> adequate supply of carbon atoms fluxing through the acetyl CoA pool

is required for

> the cholesterol synthetic process. The action of dietary restriction

on sterol

> biosynthesis is the most dramatic of any dietary perturbations

observed thus far in

> humans.

> Meal frequency ... The possible beneficial action of increasing

the number of

> meals consumed each day has been examined from several standpoints.

Reduced

> circulatory concentrations of total and low-density-lipoprotein

(LDL) cholesterol

> have been observed in individuals consuming the same amount of food

as many small

> rather than as fewer large meals each day (62). Associated with

these changes were

> lower circulating insulin concentrations, suggesting that insulin

action may be a

> potent promoter of cholesterogenesis (62). Work in humans studying

the actions of

> increased meal frequency on cholesterol synthesis reveal

cholesterogenesis rates

> about one-third less in subjects provided with meals every 4 h

around the clock

> compared with subjects given the same food as three meals per day at

normal

> mealtimes (53). Substantially reduced mean daily insulin and gastric

inhibitory

> polypeptide concentrations were observed in these nibblers,

suggesting that hormonal

> actions are responsible for the reduced cholesterol synthesis

observed (53). Insulin

> has been shown to stimulate the incorporation of labeled acetate

into cholesterol

> (63) and LDL binding and degradation (64) in vitro. Insulin may also

work indirectly

> because the activities of other enzymes associated with the

cholesterogenesis

> pathway, pyruvate dehydrogenase and phosphofructokinase, are insulin

dependent (65).

> It can be speculated that both availability of carbon-source

precursors and

> favorable hormonal profiles are essential for cholesterogenesis to

occur.

> ...

> ... The dietary factor producing the greatest change in

synthesis in humans is

> food restriction. It can be speculated that both hepatic and

extrahepatic synthesis

> declines because of the fall in circulating insulin concentrations,

as is seen with

> consumption (if evenly spaced meals or food deprivation. A direct

action of

> diminished substrate availability may further suppress whole-body

synthesis in all

> active tissues, accounting for the immediate and pronounced

reduction seen with food

> deprivation. Here, the lack of available substrate appears to be a

stronger

> suppresser of synthesis than is the absence of exogenous, dietary

cholesterol, in

> desuppressing synthesis. An important and yet unanswered question is

at what level

> of food restriction does a substantial decline in cholesterogenesis,

and circulating

> concentrations, occur. The type of dietary fat similarly influences

> cholesterogenesis in liver and perhaps intestine through regulation

of the free

> sterol pool. Hepatic PUFA may result in esterification of free

cholesterol from

> cellular regulatory pools. The decline in free cholesterol

concentrations stimulates

> the rate of sterol synthesis. The modest suppression of synthesis in

the face of

> increases in exogenous cholesterol reflects suppression of hepatic

synthesis,

> whereas extrahepatic synthesis remains relatively unaffected.

Conversely, plant

> sterols, particularly saturated sterols such as sitostanol, enhance

hepatic

> biosynthesis through reduction of the absorption of both exogenously and

> endogenously derived intestinal cholesterol, and thus, hepatic

cholesterol delivery

> via chylomicron remnants. Comparison of the response to various

dietary factors of

> human cholesterogenesis ... is summarized in Figure 2.

> Figure 2. Extent of action of dietary factors on organ

cholesterol biosynthesis

> in adult humans.

> ======================

> Diet factor Cholesterol biosynthesis

> ======================

> Food Restriction -100%

> Meal frequency -36%

> MUFA -11%

> PUFA +39%

> Cholesterol (mg/day)

> 650 -20%

> 50 +15%

> ======================

> MUFA. monounsaturated fatty acid: PUFA. polyunsaturated fatty acid.

> ... cholesterol biosynthesis rates in humans, the factor

identified as having

> the strongest influence on synthesis is negative energy balance.

Food restriction

> and weight loss have been shown to reduce both cholesterol plasma

concentrations and

> synthesis. These findings underscore the importance of energy

balance in the control

> of circulating cholesterol concentrations.

>

> -- Al Pater, alpater@...

>

> -- Al Pater, PhD; email: old542000@...

>

> __________________________________________________

>

[Guest guest]

> CRers appear to stop endogenous production of cholesterol

> effectively.

Al,

I know of at least two CRers who have had elevated cholesterol levels.

The basic problem was that they consumed mostly MUFAs and almost no

PUFAs. PUFAs include linoleic acid (C18:2) which is an omega-6

essential fatty acid that has the highest cholesterol-reducing

properties.

CR may help to lower cholesterol during a weight loss phase, but once

you reach equilibrium at your target weight, the balance of fatty

acids (sat:mufa:pufa) and the ratio of carbohydrates-to-fat play a

significant role in maintaining good lipid levels. A major

complicating factor is that the fatty acids created from carbohydrates

(de novo synthesis of fatty acids) consists primarily of palmitic acid

which increases cholesterol. A compensating amount of linoleic acid

must be available in the diet since the omega-6 fatty acids cannot be

made by the body.

Tony

====

>

> CRers appear to stop endogenous production of cholesterol

effectively. It was

> interesting to present the results for Figure 2 comparing CR with

other means of

> blood cholesterol reduction in humans. It is food for not thought?

>

>

> PJ.

> Regulation of cholesterol biosynthesis by diet in humans.

> Am J Clin Nutr. 1997 Aug;66(2):438-46. Review.

> PMID: 9250128 http://tinyurl.com/mjwoy

>

> ... Dietary factors influencing human cholesterol synthesis

include energy

> restriction, meal frequency, dietary fat type, and cholesterol and

phytosterol

> content. Food deprivation for as short as 24 h results in almost

complete cessation

> of cholesterol biosynthesis. Similarly, increased meal frequency

patterns are

> associated with a substantial depression in synthesis. In contrast,

consumption of

> oils rich in polyunsaturated fatty acids, despite reducing circulating

> concentrations, increases the cholesterol synthesis rate compared

with other fats.

> Stepwise addition of dietary cholesterol is associated with only a

modest decline in

> cholesterogenesis while raising plasma concentrations slightly. It

can be concluded

> that synthesis, as a contributor to circulating cholesterol

concentrations, is

> sensitive to many dietary factors. Energy deprivation results in the

greatest

> decline in synthesis, likely accounting for the beneficial decline

in circulating

> cholesterol concentrations observed with weight loss.

> ... Food deprivation might be anticipated to exert two possible

actions on

> cholesterol synthesis. First, if dietary cholesterol was an

important control

> element, desuppression of cholesterogenesis would occur through

removal of incoming

> dietary input. Second, and in contrast, synthesis inhibition would

be expected if

> interruption of substrate supply for cholesterogenesis was an

important regulatory

> factor. Both animal and human literature bear out that any

desuppression due to

> absence of dietary cholesterol during food deprivation is minor

compared with the

> suppression caused by the removal of energy input itself. It has

been established

> that food restriction results in a marked reduction of

cholesterogenesis in animals

> (50, 54) and moderate suppression (59-61) to almost complete

suppression (43, 52) in

> human subjects. Although correlations between excess body weight and

synthesis rates

> have been identified (59, 60), suggesting that synthesis

reequilibrates to a new

> lower level with weight loss, it has also been shown that even very

acute energy

> restriction without weight loss exerts an immediate suppression of

synthesis (43,

> 61). Food restriction may result in a decrease in available

precursor for pathways

> of lipogenesis (50, 55). These observations provide an explanation

for the reduction

> in circulating cholesterol concentrations seen with weight loss in

humans in

> negative energy balance situations. Presumably, as with fatty acid

synthesis, an

> adequate supply of carbon atoms fluxing through the acetyl CoA pool

is required for

> the cholesterol synthetic process. The action of dietary restriction

on sterol

> biosynthesis is the most dramatic of any dietary perturbations

observed thus far in

> humans.

> Meal frequency ... The possible beneficial action of increasing

the number of

> meals consumed each day has been examined from several standpoints.

Reduced

> circulatory concentrations of total and low-density-lipoprotein

(LDL) cholesterol

> have been observed in individuals consuming the same amount of food

as many small

> rather than as fewer large meals each day (62). Associated with

these changes were

> lower circulating insulin concentrations, suggesting that insulin

action may be a

> potent promoter of cholesterogenesis (62). Work in humans studying

the actions of

> increased meal frequency on cholesterol synthesis reveal

cholesterogenesis rates

> about one-third less in subjects provided with meals every 4 h

around the clock

> compared with subjects given the same food as three meals per day at

normal

> mealtimes (53). Substantially reduced mean daily insulin and gastric

inhibitory

> polypeptide concentrations were observed in these nibblers,

suggesting that hormonal

> actions are responsible for the reduced cholesterol synthesis

observed (53). Insulin

> has been shown to stimulate the incorporation of labeled acetate

into cholesterol

> (63) and LDL binding and degradation (64) in vitro. Insulin may also

work indirectly

> because the activities of other enzymes associated with the

cholesterogenesis

> pathway, pyruvate dehydrogenase and phosphofructokinase, are insulin

dependent (65).

> It can be speculated that both availability of carbon-source

precursors and

> favorable hormonal profiles are essential for cholesterogenesis to

occur.

> ...

> ... The dietary factor producing the greatest change in

synthesis in humans is

> food restriction. It can be speculated that both hepatic and

extrahepatic synthesis

> declines because of the fall in circulating insulin concentrations,

as is seen with

> consumption (if evenly spaced meals or food deprivation. A direct

action of

> diminished substrate availability may further suppress whole-body

synthesis in all

> active tissues, accounting for the immediate and pronounced

reduction seen with food

> deprivation. Here, the lack of available substrate appears to be a

stronger

> suppresser of synthesis than is the absence of exogenous, dietary

cholesterol, in

> desuppressing synthesis. An important and yet unanswered question is

at what level

> of food restriction does a substantial decline in cholesterogenesis,

and circulating

> concentrations, occur. The type of dietary fat similarly influences

> cholesterogenesis in liver and perhaps intestine through regulation

of the free

> sterol pool. Hepatic PUFA may result in esterification of free

cholesterol from

> cellular regulatory pools. The decline in free cholesterol

concentrations stimulates

> the rate of sterol synthesis. The modest suppression of synthesis in

the face of

> increases in exogenous cholesterol reflects suppression of hepatic

synthesis,

> whereas extrahepatic synthesis remains relatively unaffected.

Conversely, plant

> sterols, particularly saturated sterols such as sitostanol, enhance

hepatic

> biosynthesis through reduction of the absorption of both exogenously and

> endogenously derived intestinal cholesterol, and thus, hepatic

cholesterol delivery

> via chylomicron remnants. Comparison of the response to various

dietary factors of

> human cholesterogenesis ... is summarized in Figure 2.

> Figure 2. Extent of action of dietary factors on organ

cholesterol biosynthesis

> in adult humans.

> ======================

> Diet factor Cholesterol biosynthesis

> ======================

> Food Restriction -100%

> Meal frequency -36%

> MUFA -11%

> PUFA +39%

> Cholesterol (mg/day)

> 650 -20%

> 50 +15%

> ======================

> MUFA. monounsaturated fatty acid: PUFA. polyunsaturated fatty acid.

> ... cholesterol biosynthesis rates in humans, the factor

identified as having

> the strongest influence on synthesis is negative energy balance.

Food restriction

> and weight loss have been shown to reduce both cholesterol plasma

concentrations and

> synthesis. These findings underscore the importance of energy

balance in the control

> of circulating cholesterol concentrations.

>

> -- Al Pater, alpater@...

>

> -- Al Pater, PhD; email: old542000@...

>

> __________________________________________________

>

[Guest guest]

It appears logical to me that endogenous production would fall with CR, because we operate at a lower level and have less cholesterol turnover. Cholesterol production is a natural requirement in building/rebuilding cells, so I doubt I want to "stop" that.

It's just that high levels are associated with CVD in obesers.

The one reference indicated that high TC does not CAUSE CVD.

And it appears that 150 is about the right number, according to the AHA risk chart.

I recall there's been some discussion where the ideal number is, I don't think we know that. My risk is close to 1%.

Regards.

[ ] CR and cholesterol production

CRers appear to stop endogenous production of cholesterol effectively. It wasinteresting to present the results for Figure 2 comparing CR with other means ofblood cholesterol reduction in humans. It is food for not thought? PJ.Regulation of cholesterol biosynthesis by diet in humans.Am J Clin Nutr. 1997 Aug;66(2):438-46. Review.PMID: 9250128 http://tinyurl.com/mjwoy ... Dietary factors influencing human cholesterol synthesis include energyrestriction, meal frequency, dietary fat type, and cholesterol and phytosterolcontent. Food deprivation for as short as 24 h results in almost complete cessationof cholesterol biosynthesis. Similarly, increased meal frequency patterns areassociated with a substantial depression in synthesis. In contrast, consumption ofoils rich in polyunsaturated fatty acids, despite reducing circulatingconcentrations, increases the cholesterol synthesis rate compared with other fats.Stepwise addition of dietary cholesterol is associated with only a modest decline incholesterogenesis while raising plasma concentrations slightly. It can be concludedthat synthesis, as a contributor to circulating cholesterol concentrations, issensitive to many dietary factors. Energy deprivation results in the greatestdecline in synthesis, likely accounting for the beneficial decline in circulatingcholesterol concentrations observed with weight loss. ... Food deprivation might be anticipated to exert two possible actions oncholesterol synthesis. First, if dietary cholesterol was an important controlelement, desuppression of cholesterogenesis would occur through removal of incomingdietary input. Second, and in contrast, synthesis inhibition would be expected ifinterruption of substrate supply for cholesterogenesis was an important regulatoryfactor. Both animal and human literature bear out that any desuppression due toabsence of dietary cholesterol during food deprivation is minor compared with thesuppression caused by the removal of energy input itself. It has been establishedthat food restriction results in a marked reduction of cholesterogenesis in animals(50, 54) and moderate suppression (59-61) to almost complete suppression (43, 52) inhuman subjects. Although correlations between excess body weight and synthesis rateshave been identified (59, 60), suggesting that synthesis reequilibrates to a newlower level with weight loss, it has also been shown that even very acute energyrestriction without weight loss exerts an immediate suppression of synthesis (43,61). Food restriction may result in a decrease in available precursor for pathwaysof lipogenesis (50, 55). These observations provide an explanation for the reductionin circulating cholesterol concentrations seen with weight loss in humans innegative energy balance situations. Presumably, as with fatty acid synthesis, anadequate supply of carbon atoms fluxing through the acetyl CoA pool is required forthe cholesterol synthetic process. The action of dietary restriction on sterolbiosynthesis is the most dramatic of any dietary perturbations observed thus far inhumans. Meal frequency ... The possible beneficial action of increasing the number ofmeals consumed each day has been examined from several standpoints. Reducedcirculatory concentrations of total and low-density-lipoprotein (LDL) cholesterolhave been observed in individuals consuming the same amount of food as many smallrather than as fewer large meals each day (62). Associated with these changes werelower circulating insulin concentrations, suggesting that insulin action may be apotent promoter of cholesterogenesis (62). Work in humans studying the actions ofincreased meal frequency on cholesterol synthesis reveal cholesterogenesis ratesabout one-third less in subjects provided with meals every 4 h around the clockcompared with subjects given the same food as three meals per day at normalmealtimes (53). Substantially reduced mean daily insulin and gastric inhibitorypolypeptide concentrations were observed in these nibblers, suggesting that hormonalactions are responsible for the reduced cholesterol synthesis observed (53). Insulinhas been shown to stimulate the incorporation of labeled acetate into cholesterol(63) and LDL binding and degradation (64) in vitro. Insulin may also work indirectlybecause the activities of other enzymes associated with the cholesterogenesispathway, pyruvate dehydrogenase and phosphofructokinase, are insulin dependent (65).It can be speculated that both availability of carbon-source precursors andfavorable hormonal profiles are essential for cholesterogenesis to occur. ... ... The dietary factor producing the greatest change in synthesis in humans isfood restriction. It can be speculated that both hepatic and extrahepatic synthesisdeclines because of the fall in circulating insulin concentrations, as is seen withconsumption (if evenly spaced meals or food deprivation. A direct action ofdiminished substrate availability may further suppress whole-body synthesis in allactive tissues, accounting for the immediate and pronounced reduction seen with fooddeprivation. Here, the lack of available substrate appears to be a strongersuppresser of synthesis than is the absence of exogenous, dietary cholesterol, indesuppressing synthesis. An important and yet unanswered question is at what levelof food restriction does a substantial decline in cholesterogenesis, and circulatingconcentrations, occur. The type of dietary fat similarly influencescholesterogenesis in liver and perhaps intestine through regulation of the freesterol pool. Hepatic PUFA may result in esterification of free cholesterol fromcellular regulatory pools. The decline in free cholesterol concentrations stimulatesthe rate of sterol synthesis. The modest suppression of synthesis in the face ofincreases in exogenous cholesterol reflects suppression of hepatic synthesis,whereas extrahepatic synthesis remains relatively unaffected. Conversely, plantsterols, particularly saturated sterols such as sitostanol, enhance hepaticbiosynthesis through reduction of the absorption of both exogenously andendogenously derived intestinal cholesterol, and thus, hepatic cholesterol deliveryvia chylomicron remnants. Comparison of the response to various dietary factors ofhuman cholesterogenesis ... is summarized in Figure 2. Figure 2. Extent of action of dietary factors on organ cholesterol biosynthesisin adult humans.======================Diet factor Cholesterol biosynthesis======================Food Restriction -100%Meal frequency -36%MUFA -11%PUFA +39%Cholesterol (mg/day) 650 -20% 50 +15%======================MUFA. monounsaturated fatty acid: PUFA. polyunsaturated fatty acid. ... cholesterol biosynthesis rates in humans, the factor identified as havingthe strongest influence on synthesis is negative energy balance. Food restrictionand weight loss have been shown to reduce both cholesterol plasma concentrations andsynthesis. These findings underscore the importance of energy balance in the controlof circulating cholesterol concentrations.-- Al Pater, alpater@... -- Al Pater, PhD; email: old542000@...__________________________________________________

[Guest guest]

It appears logical to me that endogenous production would fall with CR, because we operate at a lower level and have less cholesterol turnover. Cholesterol production is a natural requirement in building/rebuilding cells, so I doubt I want to "stop" that.

It's just that high levels are associated with CVD in obesers.

The one reference indicated that high TC does not CAUSE CVD.

And it appears that 150 is about the right number, according to the AHA risk chart.

I recall there's been some discussion where the ideal number is, I don't think we know that. My risk is close to 1%.

Regards.

[ ] CR and cholesterol production

CRers appear to stop endogenous production of cholesterol effectively. It wasinteresting to present the results for Figure 2 comparing CR with other means ofblood cholesterol reduction in humans. It is food for not thought? PJ.Regulation of cholesterol biosynthesis by diet in humans.Am J Clin Nutr. 1997 Aug;66(2):438-46. Review.PMID: 9250128 http://tinyurl.com/mjwoy ... Dietary factors influencing human cholesterol synthesis include energyrestriction, meal frequency, dietary fat type, and cholesterol and phytosterolcontent. Food deprivation for as short as 24 h results in almost complete cessationof cholesterol biosynthesis. Similarly, increased meal frequency patterns areassociated with a substantial depression in synthesis. In contrast, consumption ofoils rich in polyunsaturated fatty acids, despite reducing circulatingconcentrations, increases the cholesterol synthesis rate compared with other fats.Stepwise addition of dietary cholesterol is associated with only a modest decline incholesterogenesis while raising plasma concentrations slightly. It can be concludedthat synthesis, as a contributor to circulating cholesterol concentrations, issensitive to many dietary factors. Energy deprivation results in the greatestdecline in synthesis, likely accounting for the beneficial decline in circulatingcholesterol concentrations observed with weight loss. ... Food deprivation might be anticipated to exert two possible actions oncholesterol synthesis. First, if dietary cholesterol was an important controlelement, desuppression of cholesterogenesis would occur through removal of incomingdietary input. Second, and in contrast, synthesis inhibition would be expected ifinterruption of substrate supply for cholesterogenesis was an important regulatoryfactor. Both animal and human literature bear out that any desuppression due toabsence of dietary cholesterol during food deprivation is minor compared with thesuppression caused by the removal of energy input itself. It has been establishedthat food restriction results in a marked reduction of cholesterogenesis in animals(50, 54) and moderate suppression (59-61) to almost complete suppression (43, 52) inhuman subjects. Although correlations between excess body weight and synthesis rateshave been identified (59, 60), suggesting that synthesis reequilibrates to a newlower level with weight loss, it has also been shown that even very acute energyrestriction without weight loss exerts an immediate suppression of synthesis (43,61). Food restriction may result in a decrease in available precursor for pathwaysof lipogenesis (50, 55). These observations provide an explanation for the reductionin circulating cholesterol concentrations seen with weight loss in humans innegative energy balance situations. Presumably, as with fatty acid synthesis, anadequate supply of carbon atoms fluxing through the acetyl CoA pool is required forthe cholesterol synthetic process. The action of dietary restriction on sterolbiosynthesis is the most dramatic of any dietary perturbations observed thus far inhumans. Meal frequency ... The possible beneficial action of increasing the number ofmeals consumed each day has been examined from several standpoints. Reducedcirculatory concentrations of total and low-density-lipoprotein (LDL) cholesterolhave been observed in individuals consuming the same amount of food as many smallrather than as fewer large meals each day (62). Associated with these changes werelower circulating insulin concentrations, suggesting that insulin action may be apotent promoter of cholesterogenesis (62). Work in humans studying the actions ofincreased meal frequency on cholesterol synthesis reveal cholesterogenesis ratesabout one-third less in subjects provided with meals every 4 h around the clockcompared with subjects given the same food as three meals per day at normalmealtimes (53). Substantially reduced mean daily insulin and gastric inhibitorypolypeptide concentrations were observed in these nibblers, suggesting that hormonalactions are responsible for the reduced cholesterol synthesis observed (53). Insulinhas been shown to stimulate the incorporation of labeled acetate into cholesterol(63) and LDL binding and degradation (64) in vitro. Insulin may also work indirectlybecause the activities of other enzymes associated with the cholesterogenesispathway, pyruvate dehydrogenase and phosphofructokinase, are insulin dependent (65).It can be speculated that both availability of carbon-source precursors andfavorable hormonal profiles are essential for cholesterogenesis to occur. ... ... The dietary factor producing the greatest change in synthesis in humans isfood restriction. It can be speculated that both hepatic and extrahepatic synthesisdeclines because of the fall in circulating insulin concentrations, as is seen withconsumption (if evenly spaced meals or food deprivation. A direct action ofdiminished substrate availability may further suppress whole-body synthesis in allactive tissues, accounting for the immediate and pronounced reduction seen with fooddeprivation. Here, the lack of available substrate appears to be a strongersuppresser of synthesis than is the absence of exogenous, dietary cholesterol, indesuppressing synthesis. An important and yet unanswered question is at what levelof food restriction does a substantial decline in cholesterogenesis, and circulatingconcentrations, occur. The type of dietary fat similarly influencescholesterogenesis in liver and perhaps intestine through regulation of the freesterol pool. Hepatic PUFA may result in esterification of free cholesterol fromcellular regulatory pools. The decline in free cholesterol concentrations stimulatesthe rate of sterol synthesis. The modest suppression of synthesis in the face ofincreases in exogenous cholesterol reflects suppression of hepatic synthesis,whereas extrahepatic synthesis remains relatively unaffected. Conversely, plantsterols, particularly saturated sterols such as sitostanol, enhance hepaticbiosynthesis through reduction of the absorption of both exogenously andendogenously derived intestinal cholesterol, and thus, hepatic cholesterol deliveryvia chylomicron remnants. Comparison of the response to various dietary factors ofhuman cholesterogenesis ... is summarized in Figure 2. Figure 2. Extent of action of dietary factors on organ cholesterol biosynthesisin adult humans.======================Diet factor Cholesterol biosynthesis======================Food Restriction -100%Meal frequency -36%MUFA -11%PUFA +39%Cholesterol (mg/day) 650 -20% 50 +15%======================MUFA. monounsaturated fatty acid: PUFA. polyunsaturated fatty acid. ... cholesterol biosynthesis rates in humans, the factor identified as havingthe strongest influence on synthesis is negative energy balance. Food restrictionand weight loss have been shown to reduce both cholesterol plasma concentrations andsynthesis. These findings underscore the importance of energy balance in the controlof circulating cholesterol concentrations.-- Al Pater, alpater@... -- Al Pater, PhD; email: old542000@...__________________________________________________

[Guest guest]

It just occurred to me that the paper under discussion is the same

one the abstract of which I posted last week. So thanks AL for the

precision added by the more complete version.

I was then puzzled (more than ever it seems)by the fact that,

according to the article, though PUFA consumption lowered serum

cholesterol levels it also raised its synthesis!!!???? What happens

to the cholesterol? How is it being used up? why do PUFAS have this

effect? It seems -logically- that if levels are sinking while

production goes up it means that production can't keep up???? If so

to what demand?

> >

> > CRers appear to stop endogenous production of cholesterol

> effectively. It was

> > interesting to present the results for Figure 2 comparing CR with

> other means of

> > blood cholesterol reduction in humans. It is food for not

thought?

> >

> >

> > PJ.

> > Regulation of cholesterol biosynthesis by diet in humans.

> > Am J Clin Nutr. 1997 Aug;66(2):438-46. Review.

> > PMID: 9250128 http://tinyurl.com/mjwoy

> >

> > ... Dietary factors influencing human cholesterol synthesis

> include energy

> > restriction, meal frequency, dietary fat type, and cholesterol and

> phytosterol

> > content. Food deprivation for as short as 24 h results in almost

> complete cessation

> > of cholesterol biosynthesis. Similarly, increased meal frequency

> patterns are

> > associated with a substantial depression in synthesis. In

contrast,

> consumption of

> > oils rich in polyunsaturated fatty acids, despite reducing

circulating

> > concentrations, increases the cholesterol synthesis rate compared

> with other fats.

> > Stepwise addition of dietary cholesterol is associated with only a

> modest decline in

> > cholesterogenesis while raising plasma concentrations slightly. It

> can be concluded

> > that synthesis, as a contributor to circulating cholesterol

> concentrations, is

> > sensitive to many dietary factors. Energy deprivation results in

the

> greatest

> > decline in synthesis, likely accounting for the beneficial decline

> in circulating

> > cholesterol concentrations observed with weight loss.

> > ... Food deprivation might be anticipated to exert two

possible

> actions on

> > cholesterol synthesis. First, if dietary cholesterol was an

> important control

> > element, desuppression of cholesterogenesis would occur through

> removal of incoming

> > dietary input. Second, and in contrast, synthesis inhibition would

> be expected if

> > interruption of substrate supply for cholesterogenesis was an

> important regulatory

> > factor. Both animal and human literature bear out that any

> desuppression due to

> > absence of dietary cholesterol during food deprivation is minor

> compared with the

> > suppression caused by the removal of energy input itself. It has

> been established

> > that food restriction results in a marked reduction of

> cholesterogenesis in animals

> > (50, 54) and moderate suppression (59-61) to almost complete

> suppression (43, 52) in

> > human subjects. Although correlations between excess body weight

and

> synthesis rates

> > have been identified (59, 60), suggesting that synthesis

> reequilibrates to a new

> > lower level with weight loss, it has also been shown that even

very

> acute energy

> > restriction without weight loss exerts an immediate suppression of

> synthesis (43,

> > 61). Food restriction may result in a decrease in available

> precursor for pathways

> > of lipogenesis (50, 55). These observations provide an explanation

> for the reduction

> > in circulating cholesterol concentrations seen with weight loss in

> humans in

> > negative energy balance situations. Presumably, as with fatty acid

> synthesis, an

> > adequate supply of carbon atoms fluxing through the acetyl CoA

pool

> is required for

> > the cholesterol synthetic process. The action of dietary

restriction

> on sterol

> > biosynthesis is the most dramatic of any dietary perturbations

> observed thus far in

> > humans.

> > Meal frequency ... The possible beneficial action of

increasing

> the number of

> > meals consumed each day has been examined from several

standpoints.

> Reduced

> > circulatory concentrations of total and low-density-lipoprotein

> (LDL) cholesterol

> > have been observed in individuals consuming the same amount of

food

> as many small

> > rather than as fewer large meals each day (62). Associated with

> these changes were

> > lower circulating insulin concentrations, suggesting that insulin

> action may be a

> > potent promoter of cholesterogenesis (62). Work in humans studying

> the actions of

> > increased meal frequency on cholesterol synthesis reveal

> cholesterogenesis rates

> > about one-third less in subjects provided with meals every 4 h

> around the clock

> > compared with subjects given the same food as three meals per day

at

> normal

> > mealtimes (53). Substantially reduced mean daily insulin and

gastric

> inhibitory

> > polypeptide concentrations were observed in these nibblers,

> suggesting that hormonal

> > actions are responsible for the reduced cholesterol synthesis

> observed (53). Insulin

> > has been shown to stimulate the incorporation of labeled acetate

> into cholesterol

> > (63) and LDL binding and degradation (64) in vitro. Insulin may

also

> work indirectly

> > because the activities of other enzymes associated with the

> cholesterogenesis

> > pathway, pyruvate dehydrogenase and phosphofructokinase, are

insulin

> dependent (65).

> > It can be speculated that both availability of carbon-source

> precursors and

> > favorable hormonal profiles are essential for cholesterogenesis to

> occur.

> > ...

> > ... The dietary factor producing the greatest change in

> synthesis in humans is

> > food restriction. It can be speculated that both hepatic and

> extrahepatic synthesis

> > declines because of the fall in circulating insulin

concentrations,

> as is seen with

> > consumption (if evenly spaced meals or food deprivation. A direct

> action of

> > diminished substrate availability may further suppress whole-body

> synthesis in all

> > active tissues, accounting for the immediate and pronounced

> reduction seen with food

> > deprivation. Here, the lack of available substrate appears to be a

> stronger

> > suppresser of synthesis than is the absence of exogenous, dietary

> cholesterol, in

> > desuppressing synthesis. An important and yet unanswered question

is

> at what level

> > of food restriction does a substantial decline in

cholesterogenesis,

> and circulating

> > concentrations, occur. The type of dietary fat similarly

influences

> > cholesterogenesis in liver and perhaps intestine through

regulation

> of the free

> > sterol pool. Hepatic PUFA may result in esterification of free

> cholesterol from

> > cellular regulatory pools. The decline in free cholesterol

> concentrations stimulates

> > the rate of sterol synthesis. The modest suppression of synthesis

in

> the face of

> > increases in exogenous cholesterol reflects suppression of hepatic

> synthesis,

> > whereas extrahepatic synthesis remains relatively unaffected.

> Conversely, plant

> > sterols, particularly saturated sterols such as sitostanol,

enhance

> hepatic

> > biosynthesis through reduction of the absorption of both

exogenously and

> > endogenously derived intestinal cholesterol, and thus, hepatic

> cholesterol delivery

> > via chylomicron remnants. Comparison of the response to various

> dietary factors of

> > human cholesterogenesis ... is summarized in Figure 2.

> > Figure 2. Extent of action of dietary factors on organ

> cholesterol biosynthesis

> > in adult humans.

> > ======================

> > Diet factor Cholesterol biosynthesis

> > ======================

> > Food Restriction -100%

> > Meal frequency -36%

> > MUFA -11%

> > PUFA +39%

> > Cholesterol (mg/day)

> > 650 -20%

> > 50 +15%

> > ======================

> > MUFA. monounsaturated fatty acid: PUFA. polyunsaturated fatty

acid.

> > ... cholesterol biosynthesis rates in humans, the factor

> identified as having

> > the strongest influence on synthesis is negative energy balance.

> Food restriction

> > and weight loss have been shown to reduce both cholesterol plasma

> concentrations and

> > synthesis. These findings underscore the importance of energy

> balance in the control

> > of circulating cholesterol concentrations.

> >

> > -- Al Pater, alpater@

> >

> > -- Al Pater, PhD; email: old542000@

> >

> > __________________________________________________

> >

[Guest guest]

It just occurred to me that the paper under discussion is the same

one the abstract of which I posted last week. So thanks AL for the

precision added by the more complete version.

I was then puzzled (more than ever it seems)by the fact that,

according to the article, though PUFA consumption lowered serum

cholesterol levels it also raised its synthesis!!!???? What happens

to the cholesterol? How is it being used up? why do PUFAS have this

effect? It seems -logically- that if levels are sinking while

production goes up it means that production can't keep up???? If so

to what demand?

> >

> > CRers appear to stop endogenous production of cholesterol

> effectively. It was

> > interesting to present the results for Figure 2 comparing CR with

> other means of

> > blood cholesterol reduction in humans. It is food for not

thought?

> >

> >

> > PJ.

> > Regulation of cholesterol biosynthesis by diet in humans.

> > Am J Clin Nutr. 1997 Aug;66(2):438-46. Review.

> > PMID: 9250128 http://tinyurl.com/mjwoy

> >

> > ... Dietary factors influencing human cholesterol synthesis

> include energy

> > restriction, meal frequency, dietary fat type, and cholesterol and

> phytosterol

> > content. Food deprivation for as short as 24 h results in almost

> complete cessation

> > of cholesterol biosynthesis. Similarly, increased meal frequency

> patterns are

> > associated with a substantial depression in synthesis. In

contrast,

> consumption of

> > oils rich in polyunsaturated fatty acids, despite reducing

circulating

> > concentrations, increases the cholesterol synthesis rate compared

> with other fats.

> > Stepwise addition of dietary cholesterol is associated with only a

> modest decline in

> > cholesterogenesis while raising plasma concentrations slightly. It

> can be concluded

> > that synthesis, as a contributor to circulating cholesterol

> concentrations, is

> > sensitive to many dietary factors. Energy deprivation results in

the

> greatest

> > decline in synthesis, likely accounting for the beneficial decline

> in circulating

> > cholesterol concentrations observed with weight loss.

> > ... Food deprivation might be anticipated to exert two

possible

> actions on

> > cholesterol synthesis. First, if dietary cholesterol was an

> important control

> > element, desuppression of cholesterogenesis would occur through

> removal of incoming

> > dietary input. Second, and in contrast, synthesis inhibition would

> be expected if

> > interruption of substrate supply for cholesterogenesis was an

> important regulatory

> > factor. Both animal and human literature bear out that any

> desuppression due to

> > absence of dietary cholesterol during food deprivation is minor

> compared with the

> > suppression caused by the removal of energy input itself. It has

> been established

> > that food restriction results in a marked reduction of

> cholesterogenesis in animals

> > (50, 54) and moderate suppression (59-61) to almost complete

> suppression (43, 52) in

> > human subjects. Although correlations between excess body weight

and

> synthesis rates

> > have been identified (59, 60), suggesting that synthesis

> reequilibrates to a new

> > lower level with weight loss, it has also been shown that even

very

> acute energy

> > restriction without weight loss exerts an immediate suppression of

> synthesis (43,

> > 61). Food restriction may result in a decrease in available

> precursor for pathways

> > of lipogenesis (50, 55). These observations provide an explanation

> for the reduction

> > in circulating cholesterol concentrations seen with weight loss in

> humans in

> > negative energy balance situations. Presumably, as with fatty acid

> synthesis, an

> > adequate supply of carbon atoms fluxing through the acetyl CoA

pool

> is required for

> > the cholesterol synthetic process. The action of dietary

restriction

> on sterol

> > biosynthesis is the most dramatic of any dietary perturbations

> observed thus far in

> > humans.

> > Meal frequency ... The possible beneficial action of

increasing

> the number of

> > meals consumed each day has been examined from several

standpoints.

> Reduced

> > circulatory concentrations of total and low-density-lipoprotein

> (LDL) cholesterol

> > have been observed in individuals consuming the same amount of

food

> as many small

> > rather than as fewer large meals each day (62). Associated with

> these changes were

> > lower circulating insulin concentrations, suggesting that insulin

> action may be a

> > potent promoter of cholesterogenesis (62). Work in humans studying

> the actions of

> > increased meal frequency on cholesterol synthesis reveal

> cholesterogenesis rates

> > about one-third less in subjects provided with meals every 4 h

> around the clock

> > compared with subjects given the same food as three meals per day

at

> normal

> > mealtimes (53). Substantially reduced mean daily insulin and

gastric

> inhibitory

> > polypeptide concentrations were observed in these nibblers,

> suggesting that hormonal

> > actions are responsible for the reduced cholesterol synthesis

> observed (53). Insulin

> > has been shown to stimulate the incorporation of labeled acetate

> into cholesterol

> > (63) and LDL binding and degradation (64) in vitro. Insulin may

also

> work indirectly

> > because the activities of other enzymes associated with the

> cholesterogenesis

> > pathway, pyruvate dehydrogenase and phosphofructokinase, are

insulin

> dependent (65).

> > It can be speculated that both availability of carbon-source

> precursors and

> > favorable hormonal profiles are essential for cholesterogenesis to

> occur.

> > ...

> > ... The dietary factor producing the greatest change in

> synthesis in humans is

> > food restriction. It can be speculated that both hepatic and

> extrahepatic synthesis

> > declines because of the fall in circulating insulin

concentrations,

> as is seen with

> > consumption (if evenly spaced meals or food deprivation. A direct

> action of

> > diminished substrate availability may further suppress whole-body

> synthesis in all

> > active tissues, accounting for the immediate and pronounced

> reduction seen with food

> > deprivation. Here, the lack of available substrate appears to be a

> stronger

> > suppresser of synthesis than is the absence of exogenous, dietary

> cholesterol, in

> > desuppressing synthesis. An important and yet unanswered question

is

> at what level

> > of food restriction does a substantial decline in

cholesterogenesis,

> and circulating

> > concentrations, occur. The type of dietary fat similarly

influences

> > cholesterogenesis in liver and perhaps intestine through

regulation

> of the free

> > sterol pool. Hepatic PUFA may result in esterification of free

> cholesterol from

> > cellular regulatory pools. The decline in free cholesterol

> concentrations stimulates

> > the rate of sterol synthesis. The modest suppression of synthesis

in

> the face of

> > increases in exogenous cholesterol reflects suppression of hepatic

> synthesis,

> > whereas extrahepatic synthesis remains relatively unaffected.

> Conversely, plant

> > sterols, particularly saturated sterols such as sitostanol,

enhance

> hepatic

> > biosynthesis through reduction of the absorption of both

exogenously and

> > endogenously derived intestinal cholesterol, and thus, hepatic

> cholesterol delivery

> > via chylomicron remnants. Comparison of the response to various

> dietary factors of

> > human cholesterogenesis ... is summarized in Figure 2.

> > Figure 2. Extent of action of dietary factors on organ

> cholesterol biosynthesis

> > in adult humans.

> > ======================

> > Diet factor Cholesterol biosynthesis

> > ======================

> > Food Restriction -100%

> > Meal frequency -36%

> > MUFA -11%

> > PUFA +39%

> > Cholesterol (mg/day)

> > 650 -20%

> > 50 +15%

> > ======================

> > MUFA. monounsaturated fatty acid: PUFA. polyunsaturated fatty

acid.

> > ... cholesterol biosynthesis rates in humans, the factor

> identified as having

> > the strongest influence on synthesis is negative energy balance.

> Food restriction

> > and weight loss have been shown to reduce both cholesterol plasma

> concentrations and

> > synthesis. These findings underscore the importance of energy

> balance in the control

> > of circulating cholesterol concentrations.

> >

> > -- Al Pater, alpater@

> >

> > -- Al Pater, PhD; email: old542000@

> >

> > __________________________________________________

> >

[Guest guest]

You'll have to do some research, start with

http://library.usask.ca/theses/available/etd-01232006-123919/unrestricted/g_woo.pdf

diagram on pg 10.

Regards.

[ ] Re: CR and cholesterol production

It just occurred to me that the paper under discussion is the same one the abstract of which I posted last week. So thanks AL for the precision added by the more complete version.I was then puzzled (more than ever it seems)by the fact that, according to the article, though PUFA consumption lowered serum cholesterol levels it also raised its synthesis!!!???? What happens to the cholesterol? How is it being used up? why do PUFAS have this effect? It seems -logically- that if levels are sinking while production goes up it means that production can't keep up???? If so to what demand?> >> > CRers appear to stop endogenous production of cholesterol> effectively. It was> > interesting to present the results for Figure 2 comparing CR with> other means of> > blood cholesterol reduction in humans. It is food for not thought?> > > > > > PJ.> > Regulation of cholesterol biosynthesis by diet in humans.> > Am J Clin Nutr. 1997 Aug;66(2):438-46. Review.> > PMID: 9250128 http://tinyurl.com/mjwoy> > > > ... Dietary factors influencing human cholesterol synthesis> include energy> > restriction, meal frequency, dietary fat type, and cholesterol and> phytosterol> > content. Food deprivation for as short as 24 h results in almost> complete cessation> > of cholesterol biosynthesis. Similarly, increased meal frequency> patterns are> > associated with a substantial depression in synthesis. In contrast,> consumption of> > oils rich in polyunsaturated fatty acids, despite reducing circulating> > concentrations, increases the cholesterol synthesis rate compared> with other fats.> > Stepwise addition of dietary cholesterol is associated with only a> modest decline in> > cholesterogenesis while raising plasma concentrations slightly. It> can be concluded> > that synthesis, as a contributor to circulating cholesterol> concentrations, is> > sensitive to many dietary factors. Energy deprivation results in the> greatest> > decline in synthesis, likely accounting for the beneficial decline> in circulating> > cholesterol concentrations observed with weight loss.> > ... Food deprivation might be anticipated to exert two possible> actions on> > cholesterol synthesis. First, if dietary cholesterol was an> important control> > element, desuppression of cholesterogenesis would occur through> removal of incoming> > dietary input. Second, and in contrast, synthesis inhibition would> be expected if> > interruption of substrate supply for cholesterogenesis was an> important regulatory> > factor. Both animal and human literature bear out that any> desuppression due to> > absence of dietary cholesterol during food deprivation is minor> compared with the> > suppression caused by the removal of energy input itself. It has> been established> > that food restriction results in a marked reduction of> cholesterogenesis in animals> > (50, 54) and moderate suppression (59-61) to almost complete> suppression (43, 52) in> > human subjects. Although correlations between excess body weight and> synthesis rates> > have been identified (59, 60), suggesting that synthesis> reequilibrates to a new> > lower level with weight loss, it has also been shown that even very> acute energy> > restriction without weight loss exerts an immediate suppression of> synthesis (43,> > 61). Food restriction may result in a decrease in available> precursor for pathways> > of lipogenesis (50, 55). These observations provide an explanation> for the reduction> > in circulating cholesterol concentrations seen with weight loss in> humans in> > negative energy balance situations. Presumably, as with fatty acid> synthesis, an> > adequate supply of carbon atoms fluxing through the acetyl CoA pool> is required for> > the cholesterol synthetic process. The action of dietary restriction> on sterol> > biosynthesis is the most dramatic of any dietary perturbations> observed thus far in> > humans.> > Meal frequency ... The possible beneficial action of increasing> the number of> > meals consumed each day has been examined from several standpoints.> Reduced> > circulatory concentrations of total and low-density-lipoprotein> (LDL) cholesterol> > have been observed in individuals consuming the same amount of food> as many small> > rather than as fewer large meals each day (62). Associated with> these changes were> > lower circulating insulin concentrations, suggesting that insulin> action may be a> > potent promoter of cholesterogenesis (62). Work in humans studying> the actions of> > increased meal frequency on cholesterol synthesis reveal> cholesterogenesis rates> > about one-third less in subjects provided with meals every 4 h> around the clock> > compared with subjects given the same food as three meals per day at> normal> > mealtimes (53). Substantially reduced mean daily insulin and gastric> inhibitory> > polypeptide concentrations were observed in these nibblers,> suggesting that hormonal> > actions are responsible for the reduced cholesterol synthesis> observed (53). Insulin> > has been shown to stimulate the incorporation of labeled acetate> into cholesterol> > (63) and LDL binding and degradation (64) in vitro. Insulin may also> work indirectly> > because the activities of other enzymes associated with the> cholesterogenesis> > pathway, pyruvate dehydrogenase and phosphofructokinase, are insulin> dependent (65).> > It can be speculated that both availability of carbon-source> precursors and> > favorable hormonal profiles are essential for cholesterogenesis to> occur. > > ...> > ... The dietary factor producing the greatest change in> synthesis in humans is> > food restriction. It can be speculated that both hepatic and> extrahepatic synthesis> > declines because of the fall in circulating insulin concentrations,> as is seen with> > consumption (if evenly spaced meals or food deprivation. A direct> action of> > diminished substrate availability may further suppress whole-body> synthesis in all> > active tissues, accounting for the immediate and pronounced> reduction seen with food> > deprivation. Here, the lack of available substrate appears to be a> stronger> > suppresser of synthesis than is the absence of exogenous, dietary> cholesterol, in> > desuppressing synthesis. An important and yet unanswered question is> at what level> > of food restriction does a substantial decline in cholesterogenesis,> and circulating> > concentrations, occur. The type of dietary fat similarly influences> > cholesterogenesis in liver and perhaps intestine through regulation> of the free> > sterol pool. Hepatic PUFA may result in esterification of free> cholesterol from> > cellular regulatory pools. The decline in free cholesterol> concentrations stimulates> > the rate of sterol synthesis. The modest suppression of synthesis in> the face of> > increases in exogenous cholesterol reflects suppression of hepatic> synthesis,> > whereas extrahepatic synthesis remains relatively unaffected.> Conversely, plant> > sterols, particularly saturated sterols such as sitostanol, enhance> hepatic> > biosynthesis through reduction of the absorption of both exogenously and> > endogenously derived intestinal cholesterol, and thus, hepatic> cholesterol delivery> > via chylomicron remnants. Comparison of the response to various> dietary factors of> > human cholesterogenesis ... is summarized in Figure 2.> > Figure 2. Extent of action of dietary factors on organ> cholesterol biosynthesis> > in adult humans.> > ======================> > Diet factor Cholesterol biosynthesis> > ======================> > Food Restriction -100%> > Meal frequency -36%> > MUFA -11%> > PUFA +39%> > Cholesterol (mg/day)> > 650 -20%> > 50 +15%> > ======================> > MUFA. monounsaturated fatty acid: PUFA. polyunsaturated fatty acid.> > ... cholesterol biosynthesis rates in humans, the factor> identified as having> > the strongest influence on synthesis is negative energy balance.> Food restriction> > and weight loss have been shown to reduce both cholesterol plasma> concentrations and> > synthesis. These findings underscore the importance of energy> balance in the control> > of circulating cholesterol concentrations.> > > > -- Al Pater, alpater@ > > > > -- Al Pater, PhD; email: old542000@> > > > __________________________________________________> >

[Guest guest]

You'll have to do some research, start with

http://library.usask.ca/theses/available/etd-01232006-123919/unrestricted/g_woo.pdf

diagram on pg 10.

Regards.

[ ] Re: CR and cholesterol production

It just occurred to me that the paper under discussion is the same one the abstract of which I posted last week. So thanks AL for the precision added by the more complete version.I was then puzzled (more than ever it seems)by the fact that, according to the article, though PUFA consumption lowered serum cholesterol levels it also raised its synthesis!!!???? What happens to the cholesterol? How is it being used up? why do PUFAS have this effect? It seems -logically- that if levels are sinking while production goes up it means that production can't keep up???? If so to what demand?> >> > CRers appear to stop endogenous production of cholesterol> effectively. It was> > interesting to present the results for Figure 2 comparing CR with> other means of> > blood cholesterol reduction in humans. It is food for not thought?> > > > > > PJ.> > Regulation of cholesterol biosynthesis by diet in humans.> > Am J Clin Nutr. 1997 Aug;66(2):438-46. Review.> > PMID: 9250128 http://tinyurl.com/mjwoy> > > > ... Dietary factors influencing human cholesterol synthesis> include energy> > restriction, meal frequency, dietary fat type, and cholesterol and> phytosterol> > content. Food deprivation for as short as 24 h results in almost> complete cessation> > of cholesterol biosynthesis. Similarly, increased meal frequency> patterns are> > associated with a substantial depression in synthesis. In contrast,> consumption of> > oils rich in polyunsaturated fatty acids, despite reducing circulating> > concentrations, increases the cholesterol synthesis rate compared> with other fats.> > Stepwise addition of dietary cholesterol is associated with only a> modest decline in> > cholesterogenesis while raising plasma concentrations slightly. It> can be concluded> > that synthesis, as a contributor to circulating cholesterol> concentrations, is> > sensitive to many dietary factors. Energy deprivation results in the> greatest> > decline in synthesis, likely accounting for the beneficial decline> in circulating> > cholesterol concentrations observed with weight loss.> > ... Food deprivation might be anticipated to exert two possible> actions on> > cholesterol synthesis. First, if dietary cholesterol was an> important control> > element, desuppression of cholesterogenesis would occur through> removal of incoming> > dietary input. Second, and in contrast, synthesis inhibition would> be expected if> > interruption of substrate supply for cholesterogenesis was an> important regulatory> > factor. Both animal and human literature bear out that any> desuppression due to> > absence of dietary cholesterol during food deprivation is minor> compared with the> > suppression caused by the removal of energy input itself. It has> been established> > that food restriction results in a marked reduction of> cholesterogenesis in animals> > (50, 54) and moderate suppression (59-61) to almost complete> suppression (43, 52) in> > human subjects. Although correlations between excess body weight and> synthesis rates> > have been identified (59, 60), suggesting that synthesis> reequilibrates to a new> > lower level with weight loss, it has also been shown that even very> acute energy> > restriction without weight loss exerts an immediate suppression of> synthesis (43,> > 61). Food restriction may result in a decrease in available> precursor for pathways> > of lipogenesis (50, 55). These observations provide an explanation> for the reduction> > in circulating cholesterol concentrations seen with weight loss in> humans in> > negative energy balance situations. Presumably, as with fatty acid> synthesis, an> > adequate supply of carbon atoms fluxing through the acetyl CoA pool> is required for> > the cholesterol synthetic process. The action of dietary restriction> on sterol> > biosynthesis is the most dramatic of any dietary perturbations> observed thus far in> > humans.> > Meal frequency ... The possible beneficial action of increasing> the number of> > meals consumed each day has been examined from several standpoints.> Reduced> > circulatory concentrations of total and low-density-lipoprotein> (LDL) cholesterol> > have been observed in individuals consuming the same amount of food> as many small> > rather than as fewer large meals each day (62). Associated with> these changes were> > lower circulating insulin concentrations, suggesting that insulin> action may be a> > potent promoter of cholesterogenesis (62). Work in humans studying> the actions of> > increased meal frequency on cholesterol synthesis reveal> cholesterogenesis rates> > about one-third less in subjects provided with meals every 4 h> around the clock> > compared with subjects given the same food as three meals per day at> normal> > mealtimes (53). Substantially reduced mean daily insulin and gastric> inhibitory> > polypeptide concentrations were observed in these nibblers,> suggesting that hormonal> > actions are responsible for the reduced cholesterol synthesis> observed (53). Insulin> > has been shown to stimulate the incorporation of labeled acetate> into cholesterol> > (63) and LDL binding and degradation (64) in vitro. Insulin may also> work indirectly> > because the activities of other enzymes associated with the> cholesterogenesis> > pathway, pyruvate dehydrogenase and phosphofructokinase, are insulin> dependent (65).> > It can be speculated that both availability of carbon-source> precursors and> > favorable hormonal profiles are essential for cholesterogenesis to> occur. > > ...> > ... The dietary factor producing the greatest change in> synthesis in humans is> > food restriction. It can be speculated that both hepatic and> extrahepatic synthesis> > declines because of the fall in circulating insulin concentrations,> as is seen with> > consumption (if evenly spaced meals or food deprivation. A direct> action of> > diminished substrate availability may further suppress whole-body> synthesis in all> > active tissues, accounting for the immediate and pronounced> reduction seen with food> > deprivation. Here, the lack of available substrate appears to be a> stronger> > suppresser of synthesis than is the absence of exogenous, dietary> cholesterol, in> > desuppressing synthesis. An important and yet unanswered question is> at what level> > of food restriction does a substantial decline in cholesterogenesis,> and circulating> > concentrations, occur. The type of dietary fat similarly influences> > cholesterogenesis in liver and perhaps intestine through regulation> of the free> > sterol pool. Hepatic PUFA may result in esterification of free> cholesterol from> > cellular regulatory pools. The decline in free cholesterol> concentrations stimulates> > the rate of sterol synthesis. The modest suppression of synthesis in> the face of> > increases in exogenous cholesterol reflects suppression of hepatic> synthesis,> > whereas extrahepatic synthesis remains relatively unaffected.> Conversely, plant> > sterols, particularly saturated sterols such as sitostanol, enhance> hepatic> > biosynthesis through reduction of the absorption of both exogenously and> > endogenously derived intestinal cholesterol, and thus, hepatic> cholesterol delivery> > via chylomicron remnants. Comparison of the response to various> dietary factors of> > human cholesterogenesis ... is summarized in Figure 2.> > Figure 2. Extent of action of dietary factors on organ> cholesterol biosynthesis> > in adult humans.> > ======================> > Diet factor Cholesterol biosynthesis> > ======================> > Food Restriction -100%> > Meal frequency -36%> > MUFA -11%> > PUFA +39%> > Cholesterol (mg/day)> > 650 -20%> > 50 +15%> > ======================> > MUFA. monounsaturated fatty acid: PUFA. polyunsaturated fatty acid.> > ... cholesterol biosynthesis rates in humans, the factor> identified as having> > the strongest influence on synthesis is negative energy balance.> Food restriction> > and weight loss have been shown to reduce both cholesterol plasma> concentrations and> > synthesis. These findings underscore the importance of energy> balance in the control> > of circulating cholesterol concentrations.> > > > -- Al Pater, alpater@ > > > > -- Al Pater, PhD; email: old542000@> > > > __________________________________________________> >