Re: Re: Carbohydrate restriction regulates the adaptive response to fasting

[Guest guest]

A ketogenic diet may " mimic " the way the body is forced to use energy during CR,

but it is not without some very serious side effects. Yes, it is used

occasionally on a limited basis to treat epilepsy, but again, there are serious

consequences and the patients are not kept on the diet more than 2 years.

You may want to check out the study by Kwiterovich who studies the effects of

such a diet on children over the course of 6 months to 2 years (see abstract

below)

Regards

Jeff.

JAMA. 2003 Aug 20;290(7):912-20.

Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins,

and apolipoproteins in children.

Kwiterovich PO Jr

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & term=%22Kwit\

erovich+PO+Jr%22%5BAuthor%5D> , Vining EP

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & term=%22Vini\

ng+EP%22%5BAuthor%5D> , Pyzik P

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & term=%22Pyzi\

k+P%22%5BAuthor%5D> , Skolasky R Jr

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & term=%22Skol\

asky+R+Jr%22%5BAuthor%5D> , Freeman JM

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & term=%22Free\

man+JM%22%5BAuthor%5D> .

Lipid Research Atherosclerosis Division, Department of Neurology, The s

Hopkins Medical Institutions, Baltimore, Md, USA. pkwitero@...

CONTEXT: Little prospective long-term information is available on the effect of

a ketogenic diet on plasma lipoproteins in children with difficult-to-control

seizures.

OBJECTIVE: To determine the effect in children with intractable seizures of a

high-fat ketogenic diet on plasma levels of the major apolipoprotein B

(apoB)-containing lipoproteins, low-density lipoprotein (LDL) and very LDL

(VLDL); and the major apolipoprotein A-I (apoA-I)-containing lipoprotein,

high-density lipoprotein (HDL).

DESIGN, SETTING, AND PATIENTS: A 6-month prospective cohort study of 141

children (mean [sD] age, 5.2 [3.8] years for 70 boys and 6.1 [4.4] years for 71

girls) with difficult-to-treat seizures who were hospitalized for initiation of

a high-fat ketogenic diet and followed up as outpatients. This cohort

constituted a subgroup of the 371 patients accepted into the ketogenic diet

program between 1994 and 2001. A subset of the cohort was also studied after 12

(n = 59) and 24 (n = 27) months.

INTERVENTION: A ketogenic diet consisting of a high ratio of fat to carbohydrate

and protein combined (4:1 [n = 102], 3.5:1 [n = 7], or 3:1 [n = 32]). After diet

initiation, the calories and ratio were adjusted to maintain ideal body weight

for height and maximal urinary ketosis for seizure control.

MAIN OUTCOME MEASURES: Differences at baseline and 6-month follow-up for levels

of total, VLDL, LDL, HDL, and non-HDL cholesterol; triglycerides; total apoB;

and apoA-I.

RESULTS: At 6 months, the high-fat ketogenic diet significantly increased the

mean plasma levels of total (58 mg/dL [1.50 mmol/L]), LDL (50 mg/dL [1.30

mmol/L]), VLDL (8 mg/dL [0.21 mmol/L]), and non-HDL cholesterol (63 mg/dL [1.63

mmol/L]) (P<.001 vs baseline for each); triglycerides (58 mg/dL [0.66 mmol/L])

(P<.001); and total apoB (49 mg/dL) (P<.001). Mean HDL cholesterol decreased

significantly (P<.001), although apoA-I increased (4 mg/dL) (P =.23).

Significant but less marked changes persisted in children observed after 12 and

24 months.

CONCLUSIONS: A high-fat ketogenic diet produced significant increases in the

atherogenic apoB-containing lipoproteins and a decrease in the antiatherogenic

HDL cholesterol. Further studies are necessary to determine if such a diet

adversely affects endothelial vascular function and promotes inflammation and

formation of atherosclerotic lesions.

[Guest guest]

A ketogenic diet may " mimic " the way the body is forced to use energy during CR,

but it is not without some very serious side effects. Yes, it is used

occasionally on a limited basis to treat epilepsy, but again, there are serious

consequences and the patients are not kept on the diet more than 2 years.

You may want to check out the study by Kwiterovich who studies the effects of

such a diet on children over the course of 6 months to 2 years (see abstract

below)

Regards

Jeff.

JAMA. 2003 Aug 20;290(7):912-20.

Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins,

and apolipoproteins in children.

Kwiterovich PO Jr

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & term=%22Kwit\

erovich+PO+Jr%22%5BAuthor%5D> , Vining EP

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & term=%22Vini\

ng+EP%22%5BAuthor%5D> , Pyzik P

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & term=%22Pyzi\

k+P%22%5BAuthor%5D> , Skolasky R Jr

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & term=%22Skol\

asky+R+Jr%22%5BAuthor%5D> , Freeman JM

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & term=%22Free\

man+JM%22%5BAuthor%5D> .

Lipid Research Atherosclerosis Division, Department of Neurology, The s

Hopkins Medical Institutions, Baltimore, Md, USA. pkwitero@...

CONTEXT: Little prospective long-term information is available on the effect of

a ketogenic diet on plasma lipoproteins in children with difficult-to-control

seizures.

OBJECTIVE: To determine the effect in children with intractable seizures of a

high-fat ketogenic diet on plasma levels of the major apolipoprotein B

(apoB)-containing lipoproteins, low-density lipoprotein (LDL) and very LDL

(VLDL); and the major apolipoprotein A-I (apoA-I)-containing lipoprotein,

high-density lipoprotein (HDL).

DESIGN, SETTING, AND PATIENTS: A 6-month prospective cohort study of 141

children (mean [sD] age, 5.2 [3.8] years for 70 boys and 6.1 [4.4] years for 71

girls) with difficult-to-treat seizures who were hospitalized for initiation of

a high-fat ketogenic diet and followed up as outpatients. This cohort

constituted a subgroup of the 371 patients accepted into the ketogenic diet

program between 1994 and 2001. A subset of the cohort was also studied after 12

(n = 59) and 24 (n = 27) months.

INTERVENTION: A ketogenic diet consisting of a high ratio of fat to carbohydrate

and protein combined (4:1 [n = 102], 3.5:1 [n = 7], or 3:1 [n = 32]). After diet

initiation, the calories and ratio were adjusted to maintain ideal body weight

for height and maximal urinary ketosis for seizure control.

MAIN OUTCOME MEASURES: Differences at baseline and 6-month follow-up for levels

of total, VLDL, LDL, HDL, and non-HDL cholesterol; triglycerides; total apoB;

and apoA-I.

RESULTS: At 6 months, the high-fat ketogenic diet significantly increased the

mean plasma levels of total (58 mg/dL [1.50 mmol/L]), LDL (50 mg/dL [1.30

mmol/L]), VLDL (8 mg/dL [0.21 mmol/L]), and non-HDL cholesterol (63 mg/dL [1.63

mmol/L]) (P<.001 vs baseline for each); triglycerides (58 mg/dL [0.66 mmol/L])

(P<.001); and total apoB (49 mg/dL) (P<.001). Mean HDL cholesterol decreased

significantly (P<.001), although apoA-I increased (4 mg/dL) (P =.23).

Significant but less marked changes persisted in children observed after 12 and

24 months.

CONCLUSIONS: A high-fat ketogenic diet produced significant increases in the

atherogenic apoB-containing lipoproteins and a decrease in the antiatherogenic

HDL cholesterol. Further studies are necessary to determine if such a diet

adversely affects endothelial vascular function and promotes inflammation and

formation of atherosclerotic lesions.

[Guest guest]

All is vanity.....

On 10/23/05, drsusanforshey <drsusanforshey@...> wrote:

It's a surprise to me. I eat a very high carb (leafy greens, crucifersetc), and very very low FAT diet. Fasting has documented physiologic

benefits and if restricting carbs mimics the effects of a fastingstate perhaps this outweighs any purported " antioxidant " benefits fromhuge consumption of plants. Seems to me that this suggests perhaps

Caloric restriction with ADEQUATE nutrition (and low carbs) trumpsCaloric Restriction with SUPRA nutrition. (or am i reading too muchinto this?)Is it best to CRAN with restricted carbs, OR CRSN consuming mainly

leafy greens, crucifers etc??? IOW, what % of various macro's is CRON,as it may be known at this time?> > Hmmm....> >> > " These results demonstrate that restriction of dietary carbohydrate,> > not the general absence of energy intake itself, is responsible for

> > initiating the metabolic response to short-term fasting. " > >> > I don't know what to make of this but sounds interesting > >> > Can we get full text?> >

> >> >> >> > Am J Physiol. 1992 May;262(5 Pt 1):E631-6.> >> > Carbohydrate restriction regulates the adaptive response tofasting.> >> > Klein S, Wolfe RR.

> >> > Department of Internal Medicine, University of Texas Medical> > Branch, Galveston.> >> >> >>> I don't know that this is very surprising. Carbohydrate restriction

> forces our body into a ketogenic energy cycle (fat conversion to asugar> equivalent to keep brain et al happy). Adkins and others have exploited> this energy pathway for quick water loss (from glycogen reduction) and

> other apparent short term benefits. To begin fasting while the body is> already burning primarily fat would be a fairly modest shift towhere it> gets that fat from than a major " source of energy " transition. Just

> because we stop eating, doesn't mean the body doesn't still need andget> it's fuel.>> I suspect this shift to fat only energy metabolism is the source ofmuch> discomfort for first time fasters, especially if their body hasn't

> experienced a low carbohydrate state previously. There have been> suggestions that our brains run better on ketones than sugar and some> research has suggested that as beneficial for epilepsy sufferers. IMO

> pretty interesting stuff...>> JR>

[Guest guest]

All is vanity.....

On 10/23/05, drsusanforshey <drsusanforshey@...> wrote:

It's a surprise to me. I eat a very high carb (leafy greens, crucifersetc), and very very low FAT diet. Fasting has documented physiologic

benefits and if restricting carbs mimics the effects of a fastingstate perhaps this outweighs any purported " antioxidant " benefits fromhuge consumption of plants. Seems to me that this suggests perhaps

Caloric restriction with ADEQUATE nutrition (and low carbs) trumpsCaloric Restriction with SUPRA nutrition. (or am i reading too muchinto this?)Is it best to CRAN with restricted carbs, OR CRSN consuming mainly

leafy greens, crucifers etc??? IOW, what % of various macro's is CRON,as it may be known at this time?> > Hmmm....> >> > " These results demonstrate that restriction of dietary carbohydrate,> > not the general absence of energy intake itself, is responsible for

> > initiating the metabolic response to short-term fasting. " > >> > I don't know what to make of this but sounds interesting > >> > Can we get full text?> >

> >> >> >> > Am J Physiol. 1992 May;262(5 Pt 1):E631-6.> >> > Carbohydrate restriction regulates the adaptive response tofasting.> >> > Klein S, Wolfe RR.

> >> > Department of Internal Medicine, University of Texas Medical> > Branch, Galveston.> >> >> >>> I don't know that this is very surprising. Carbohydrate restriction

> forces our body into a ketogenic energy cycle (fat conversion to asugar> equivalent to keep brain et al happy). Adkins and others have exploited> this energy pathway for quick water loss (from glycogen reduction) and

> other apparent short term benefits. To begin fasting while the body is> already burning primarily fat would be a fairly modest shift towhere it> gets that fat from than a major " source of energy " transition. Just

> because we stop eating, doesn't mean the body doesn't still need andget> it's fuel.>> I suspect this shift to fat only energy metabolism is the source ofmuch> discomfort for first time fasters, especially if their body hasn't

> experienced a low carbohydrate state previously. There have been> suggestions that our brains run better on ketones than sugar and some> research has suggested that as beneficial for epilepsy sufferers. IMO

> pretty interesting stuff...>> JR>

[Guest guest]

drsusanforshey wrote:

> It's a surprise to me. I eat a very high carb (leafy greens, crucifers

> etc), and very very low FAT diet. Fasting has documented physiologic

> benefits and if restricting carbs mimics the effects of a fasting

> state perhaps this outweighs any purported " antioxidant " benefits from

> huge consumption of plants. Seems to me that this suggests perhaps

> Caloric restriction with ADEQUATE nutrition (and low carbs) trumps

> Caloric Restriction with SUPRA nutrition. (or am i reading too much

> into this?)

>

> Is it best to CRAN with restricted carbs, OR CRSN consuming mainly

> leafy greens, crucifers etc??? IOW, what % of various macro's is CRON,

> as it may be known at this time?

>

>

>

>

>>> Hmmm....

>>>

>>> " These results demonstrate that restriction of dietary carbohydrate,

>>> not the general absence of energy intake itself, is responsible for

>>> initiating the metabolic response to short-term fasting. "

>>>

>>> I don't know what to make of this but sounds interesting

>>>

>>> Can we get full text?

>>>

>>>

>>>

>>>

>>> Am J Physiol. 1992 May;262(5 Pt 1):E631-6.

>>>

>>> Carbohydrate restriction regulates the adaptive response to

> fasting.

>>> Klein S, Wolfe RR.

>>>

>>> Department of Internal Medicine, University of Texas Medical

>>> Branch, Galveston.

>>>

>>>

>>>

>> I don't know that this is very surprising. Carbohydrate restriction

>> forces our body into a ketogenic energy cycle (fat conversion to a

> sugar

>> equivalent to keep brain et al happy). Adkins and others have exploited

>> this energy pathway for quick water loss (from glycogen reduction) and

>> other apparent short term benefits. To begin fasting while the body is

>> already burning primarily fat would be a fairly modest shift to

> where it

>> gets that fat from than a major " source of energy " transition. Just

>> because we stop eating, doesn't mean the body doesn't still need and

> get

>> it's fuel.

>>

>> I suspect this shift to fat only energy metabolism is the source of

> much

>> discomfort for first time fasters, especially if their body hasn't

>> experienced a low carbohydrate state previously. There have been

>> suggestions that our brains run better on ketones than sugar and some

>> research has suggested that as beneficial for epilepsy sufferers. IMO

>> pretty interesting stuff...

>>

>> JR

>>

>

>

>

>

>

As Jeff said, it only mimics the energy pathway. The benefits suggested

for fasting and I am inclined to believe there can be some benefit,

probably comes from not only exercising this energy pathway but resting

the digestive system and perhaps reseting our internal flora.

If carbohydrate restriction was even remotely equivalent to fasting

Adkins's diet would have turned out far healthier. Knocking out any

important (essential?) food group long term isn't likely to be good.

I still suspect energy restriction trumps gaming macro nutrient ratios

even to knock out extremes.

JR

[Guest guest]

drsusanforshey wrote:

> It's a surprise to me. I eat a very high carb (leafy greens, crucifers

> etc), and very very low FAT diet. Fasting has documented physiologic

> benefits and if restricting carbs mimics the effects of a fasting

> state perhaps this outweighs any purported " antioxidant " benefits from

> huge consumption of plants. Seems to me that this suggests perhaps

> Caloric restriction with ADEQUATE nutrition (and low carbs) trumps

> Caloric Restriction with SUPRA nutrition. (or am i reading too much

> into this?)

>

> Is it best to CRAN with restricted carbs, OR CRSN consuming mainly

> leafy greens, crucifers etc??? IOW, what % of various macro's is CRON,

> as it may be known at this time?

>

>

>

>

>>> Hmmm....

>>>

>>> " These results demonstrate that restriction of dietary carbohydrate,

>>> not the general absence of energy intake itself, is responsible for

>>> initiating the metabolic response to short-term fasting. "

>>>

>>> I don't know what to make of this but sounds interesting

>>>

>>> Can we get full text?

>>>

>>>

>>>

>>>

>>> Am J Physiol. 1992 May;262(5 Pt 1):E631-6.

>>>

>>> Carbohydrate restriction regulates the adaptive response to

> fasting.

>>> Klein S, Wolfe RR.

>>>

>>> Department of Internal Medicine, University of Texas Medical

>>> Branch, Galveston.

>>>

>>>

>>>

>> I don't know that this is very surprising. Carbohydrate restriction

>> forces our body into a ketogenic energy cycle (fat conversion to a

> sugar

>> equivalent to keep brain et al happy). Adkins and others have exploited

>> this energy pathway for quick water loss (from glycogen reduction) and

>> other apparent short term benefits. To begin fasting while the body is

>> already burning primarily fat would be a fairly modest shift to

> where it

>> gets that fat from than a major " source of energy " transition. Just

>> because we stop eating, doesn't mean the body doesn't still need and

> get

>> it's fuel.

>>

>> I suspect this shift to fat only energy metabolism is the source of

> much

>> discomfort for first time fasters, especially if their body hasn't

>> experienced a low carbohydrate state previously. There have been

>> suggestions that our brains run better on ketones than sugar and some

>> research has suggested that as beneficial for epilepsy sufferers. IMO

>> pretty interesting stuff...

>>

>> JR

>>

>

>

>

>

>

As Jeff said, it only mimics the energy pathway. The benefits suggested

for fasting and I am inclined to believe there can be some benefit,

probably comes from not only exercising this energy pathway but resting

the digestive system and perhaps reseting our internal flora.

If carbohydrate restriction was even remotely equivalent to fasting

Adkins's diet would have turned out far healthier. Knocking out any

important (essential?) food group long term isn't likely to be good.

I still suspect energy restriction trumps gaming macro nutrient ratios

even to knock out extremes.

JR

[Guest guest]

Respectfully, Dr Forshey, I doubt you've experienced the effects of a very low fat diet yet, ie, skin problems, or severe constipation caused by too much fiber. Some CRONies have.

AFAIC, there is no optimum in CRON if it causes medical problems, and there are medical problems that docs just don't know about.

Best for anyone to be cautious adopting any diet that others use. Like we can try cutting out one big mac from our diet of 3 per day (ha) to start.

I found most of my problems were from too MUCH nutrition, not the dispersion of macros.

There is no panacea.

Regards.

[ ] Re: Carbohydrate restriction regulates the adaptive response to fasting

It's a surprise to me. I eat a very high carb (leafy greens, crucifersetc), and very very low FAT diet. Fasting has documented physiologicbenefits and if restricting carbs mimics the effects of a fastingstate perhaps this outweighs any purported "antioxidant" benefits fromhuge consumption of plants. Seems to me that this suggests perhapsCaloric restriction with ADEQUATE nutrition (and low carbs) trumpsCaloric Restriction with SUPRA nutrition. (or am i reading too muchinto this?)Is it best to CRAN with restricted carbs, OR CRSN consuming mainlyleafy greens, crucifers etc??? IOW, what % of various macro's is CRON,as it may be known at this time?

[Guest guest]

Respectfully, Dr Forshey, I doubt you've experienced the effects of a very low fat diet yet, ie, skin problems, or severe constipation caused by too much fiber. Some CRONies have.

AFAIC, there is no optimum in CRON if it causes medical problems, and there are medical problems that docs just don't know about.

Best for anyone to be cautious adopting any diet that others use. Like we can try cutting out one big mac from our diet of 3 per day (ha) to start.

I found most of my problems were from too MUCH nutrition, not the dispersion of macros.

There is no panacea.

Regards.

[ ] Re: Carbohydrate restriction regulates the adaptive response to fasting

It's a surprise to me. I eat a very high carb (leafy greens, crucifersetc), and very very low FAT diet. Fasting has documented physiologicbenefits and if restricting carbs mimics the effects of a fastingstate perhaps this outweighs any purported "antioxidant" benefits fromhuge consumption of plants. Seems to me that this suggests perhapsCaloric restriction with ADEQUATE nutrition (and low carbs) trumpsCaloric Restriction with SUPRA nutrition. (or am i reading too muchinto this?)Is it best to CRAN with restricted carbs, OR CRSN consuming mainlyleafy greens, crucifers etc??? IOW, what % of various macro's is CRON,as it may be known at this time?

[Guest guest]

Hi All,

See the pdf-available paper below that suggests that it is the carbohydrate

levels,

not calories in general, that matter in fasting effects.

Klein S, Wolfe RR.

Carbohydrate restriction regulates the adaptive response to fasting.

Am J Physiol. 1992 May;262(5 Pt 1):E631-6.

PMID: 1590373

The importance of either carbohydrate or energy restriction in initiating the

metabolic response to fasting was studied in five normal volunteers. The

subjects

participated in two study protocols in a randomized crossover fashion. In one

study

the subjects fasted for 84 h (control study), and in the other a lipid emulsion

was

infused daily to meet resting energy requirements during the 84-h oral fast

(lipid

study). Glycerol and palmitic acid rates of appearance in plasma were determined

by

infusing [2H5]glycerol and [1-13C]palmitic acid, respectively, after 12 and 84 h

of

oral fasting. Changes in plasma glucose, free fatty acids, ketone bodies,

insulin,

and epinephrine concentrations during fasting were the same in both the control

and

lipid studies. Glycerol and palmitic acid rates of appearance increased by 1.63

+/-

0.42 and 1.41 +/- 0.46 mumol.kg-1.min-1, respectively, during fasting in the

control

study and by 1.35 +/- 0.41 and 1.43 +/- 0.44 mumol.kg-1.min-1, respectively, in

the

lipid study. These results demonstrate that restriction of dietary carbohydrate,

not

the general absence of energy intake itself, is responsible for initiating the

metabolic response to short-term fasting.

.... Each subject served as his own control and com-

pleted two study protocols separated by a 3-wk interval in a

randomized crossover fashion. In one study the subjects fasted

for 84 h, whereas, in the other, lipid calories were given intra-

venously during “fasting” to meet resting energy requirements.

All subjects were admitted to the CRC at The University of

Texas Medical Branch and were given a standard meal in the

afternoon and evening. After an overnight (12-h) fast

.... After the infusion study was completed, the subjects random-

ized to complete fasting continued to fast for another 72 h (84 h

total), being given only water, vitamins, potassium chloride (40

meq/day), and sodium chloride (8 g/day) orally. At 84 h of

fasting, the infusion protocol and indirect calorimetry measure-

ments performed after 12 h of fasting were repeated. The sub-

jects randomized to receive lipid calories during fasting were

given a commercial lipid emulsion (Intralipid 20%, Clintec

Nutrition, Deerfield, IL) intravenously during the fasting period

and also received water, vitamins, and electrolytes orally. The

lipid emulsion contained lipid calories in the form of soybean oil

at a concentration of 20 g/dl, phospholipids (1.2 g/dl), and small

amounts of glycerol (2.25 g/dl). Intralipid was infused for 15 h

each day to simulate normal cycles of daytime feeding and

nighttime fasting. On the first day of fasting, Intralipid was

infused after the first isotope infusion study was completed

from 1100 to 0200 h. Plasma triglyceride concentration was

measured 5 h after starting the lipid infusion to ensure adequate

clearance. Intralipid was infused from 0600 to 2100 h during

each subsequent day of fasting. The rate at which the lipid

emulsion was infused was calculated to meet the measured

RMR. After 84 h of fasting with daily lipid infusions (12 h after

completing the final day’s lipid infusion), the isotope infusion

protocol and indirect calorimetry measurements performed

after 12 h of fasting were repeated.

.... After completion of the first fasting study, all subjects con-

sumed a weight-maintaining free-choice diet for 3 wk as

outpatients. The subjects were then readmitted to the CRC

where they completed the second fasting (either with or without

concomitant lipid infusion) study.

.... RESULTS

Data on energy, protein, and fluid balance during fast-

ing are shown in Table 1. Infusion of the lipid emulsion

during fasting provided 5% more calories daily than the

measured resting energy requirements but provided only

19±2 g of carbohydrate calories as glycerol per day.

Weight loss, measured between 12 and 84 h of fasting, was

0.78±0.16 kg greater (P = 0.008) during the control

study than during the lipid study. Nitrogen excretion

during fasting was the same in both studies. Fluid balance

was more negative during the control study than during

the lipid study because of the administration of intrave-

nous fluids during the lipid study, but the differences in

fluid balance were not statistically significant.

Table 1. Metabolic factors during 12 and 84 h of fasting

============

Control study Lipid study

============

Weight loss, kg 2.64±0.13 1.86±0.22*

Measured resting metabolic rate, kcal/kg/day-l 22±l 22±l

Lipid emulsion infused, kcal/kg/day-l 0 23±l

Glycerol infused, g/day 0 19±2

Urinary nitrogen excretion, g/72 h 23.9±3 26.1±3

Fluid balance, ml/72 h -2,761±470 -2,194±133

================

Values are means ± SE.

Fluid balance was fluid intake minus fluid output in urine and estimated

insensible

loss of 800 ml/day.

Significantly different from control value, * P = 0.008.

The plasma substrate and hormone concentrations

after 12 and 84 h of fasting are shown in Table 2.

As expected, plasma glucose and insulin decreased, whereas

total free fatty acids, ketone bodies, and epinephrine

increased after fasting in the control study. Changes in

substrates and hormones were the same in the lipid study

as those during the control study despite the daily infu-

sion of lipid calories. There was no significant change in

plasma norepinephrine after fasting in either the control

or lipid studies. Lipid infusion on the first day of fasting

caused a fourfold increase in plasma triglyceride

concentration. Plasma triglycerides increased from 68±26

mg/dl in the basal state to 278±58 mg/dl at 5 h of

lipid infusion. Basal triglycerides did not change after 84

h of fasting in the control study but increased by -60%

after 84 h of fasting (12 h after stopping the infusion of

Intralipid) in the lipid study. The difference in triglycer-

ide levels in the lipid study, however, were not statisti-

cally significant because of the small sample size and the

variability in the data.

Table 2. Plasma substrate and hormone concentration

=================

Control study Lipid study

12-h fast 84-h fast 12-h fast 84-h fast

=================

Glucose, mg/dl 92±2 68±2* 86±2 66±3*

Free fatty acid, µM 376±92 917±61* 487±66 1,023±80*

Triglyceride, mg/d1 57±lO 61±8 68±26 109±33

Acetoacetate, µM 72±8 1,060±213* 74±ll 980±80*

ß-Hydroxybutyrate, µM 84±20 2,560±370* 108±50 2,540±440*

Insulin, µU/ml 7.5±O.7 2.720.2±6.7k0.7 68+12t 3.2±O.l*

Epinephrine, pg/ml 39±8 68±26† 42±9 70±15†

Norepinephrine, ng/ml 142±21 194±45 179±15 163±25

=================

Values are means ± SE.

For lipid study, 84-h fast was 12 h after stopping lipid emulsion infusion.

Significantly different from corresponding 12-h value, *P < 0.001, †P < 0.01.

Lipolytic rates and the absolute increase in the Ra of

glycerol and palmitic acid during fasting were similar in

both the control and lipid studies (Fig. 1). Glycerol Ra

increased by 1.63±0.42 µmol/kg/min (from 1.94±

0.30 to 3.57±0.21 µmol/kg/min after 12 and 84 h of

total fasting, respectively) in the control study (P <

0.001) and by 1.35±0.41 µmol/kg/min (from 2.28±

0.12 to 3.63±0.41 µmol/kg/min after 12 and 84 h of

fasting plus daily lipid infusions, respectively) in the lipid

study (P <0.001). Palmitic acid Ra increased by 1.41±0.46

µmol/kg/min (from 1.50±0.35 to 2.91±0.23 µmol/kg/min

after 12 and 84 h of total fasting,

respectively) in the control study (P < 0.001) and by 1.43

±0.44 µmol/kg/min (from 1.57±0.23 to 3.01±0.32 -

µmol/kg/min after 12 and 84 h of fasting plus daily

lipid infusions, respectively) in the lipid study (P <

0.001).

Triglyceride oxidation increased during fasting in both

the control and lipid studies (P < 0.001; Fig. 1). Daily

lipid infusion did not affect the rate of triglyceride oxi-

dation, and the values at 12 and 84 h of fasting were

similar in both studies. The rates of triglyceride oxidation

in the control and lipid studies were 1.07±0.09 and 1.13

±0.17 µmol/kg/min, respectively, after 12 h of fast-

ing and 1.77±0.10 and 1.67±0.08 µmol/kg/min,

respectively, after 84 h of fasting. The percentage of

released fatty acids that were oxidized for fuel was also

the same in both studies and remained constant during

fasting. Approximately 50% of mobilized triglycerides

were oxidized after both 12 and 84 h of fasting.

The rate of total triglyceride recycling was similar in

both the control and lipid studies (Fig. 1). Total triglyc-

eride recycling increased from 0.87±0.31 to 1.80±0.23

µmol/kg/min after 12 and 84 h of fasting, respec-

tively, in the control study (P < 0.01) and from 1.15±0.15

to 1.96±0.37 µmol/kg/min, respectively, in the

lipid study (P < 0.01). The rate of intracellular adipocyte

triglyceride recycling was similar in both studies because

the relationship between palmitic acid Ra and glycerol Ra,

an index of intracellular recycling, was similar. The esti-

mated energy cost of total triglyceride recycling was min-

imal and accounted for - 1 and -2% of the daily RMR

after 12 and 84 h of fasting, respectively. ...

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

__________________________________

- PC Magazine Editors' Choice 2005

http://mail.

[Guest guest]

Hi All,

See the pdf-available paper below that suggests that it is the carbohydrate

levels,

not calories in general, that matter in fasting effects.

Klein S, Wolfe RR.

Carbohydrate restriction regulates the adaptive response to fasting.

Am J Physiol. 1992 May;262(5 Pt 1):E631-6.

PMID: 1590373

The importance of either carbohydrate or energy restriction in initiating the

metabolic response to fasting was studied in five normal volunteers. The

subjects

participated in two study protocols in a randomized crossover fashion. In one

study

the subjects fasted for 84 h (control study), and in the other a lipid emulsion

was

infused daily to meet resting energy requirements during the 84-h oral fast

(lipid

study). Glycerol and palmitic acid rates of appearance in plasma were determined

by

infusing [2H5]glycerol and [1-13C]palmitic acid, respectively, after 12 and 84 h

of

oral fasting. Changes in plasma glucose, free fatty acids, ketone bodies,

insulin,

and epinephrine concentrations during fasting were the same in both the control

and

lipid studies. Glycerol and palmitic acid rates of appearance increased by 1.63

+/-

0.42 and 1.41 +/- 0.46 mumol.kg-1.min-1, respectively, during fasting in the

control

study and by 1.35 +/- 0.41 and 1.43 +/- 0.44 mumol.kg-1.min-1, respectively, in

the

lipid study. These results demonstrate that restriction of dietary carbohydrate,

not

the general absence of energy intake itself, is responsible for initiating the

metabolic response to short-term fasting.

.... Each subject served as his own control and com-

pleted two study protocols separated by a 3-wk interval in a

randomized crossover fashion. In one study the subjects fasted

for 84 h, whereas, in the other, lipid calories were given intra-

venously during “fasting” to meet resting energy requirements.

All subjects were admitted to the CRC at The University of

Texas Medical Branch and were given a standard meal in the

afternoon and evening. After an overnight (12-h) fast

.... After the infusion study was completed, the subjects random-

ized to complete fasting continued to fast for another 72 h (84 h

total), being given only water, vitamins, potassium chloride (40

meq/day), and sodium chloride (8 g/day) orally. At 84 h of

fasting, the infusion protocol and indirect calorimetry measure-

ments performed after 12 h of fasting were repeated. The sub-

jects randomized to receive lipid calories during fasting were

given a commercial lipid emulsion (Intralipid 20%, Clintec

Nutrition, Deerfield, IL) intravenously during the fasting period

and also received water, vitamins, and electrolytes orally. The

lipid emulsion contained lipid calories in the form of soybean oil

at a concentration of 20 g/dl, phospholipids (1.2 g/dl), and small

amounts of glycerol (2.25 g/dl). Intralipid was infused for 15 h

each day to simulate normal cycles of daytime feeding and

nighttime fasting. On the first day of fasting, Intralipid was

infused after the first isotope infusion study was completed

from 1100 to 0200 h. Plasma triglyceride concentration was

measured 5 h after starting the lipid infusion to ensure adequate

clearance. Intralipid was infused from 0600 to 2100 h during

each subsequent day of fasting. The rate at which the lipid

emulsion was infused was calculated to meet the measured

RMR. After 84 h of fasting with daily lipid infusions (12 h after

completing the final day’s lipid infusion), the isotope infusion

protocol and indirect calorimetry measurements performed

after 12 h of fasting were repeated.

.... After completion of the first fasting study, all subjects con-

sumed a weight-maintaining free-choice diet for 3 wk as

outpatients. The subjects were then readmitted to the CRC

where they completed the second fasting (either with or without

concomitant lipid infusion) study.

.... RESULTS

Data on energy, protein, and fluid balance during fast-

ing are shown in Table 1. Infusion of the lipid emulsion

during fasting provided 5% more calories daily than the

measured resting energy requirements but provided only

19±2 g of carbohydrate calories as glycerol per day.

Weight loss, measured between 12 and 84 h of fasting, was

0.78±0.16 kg greater (P = 0.008) during the control

study than during the lipid study. Nitrogen excretion

during fasting was the same in both studies. Fluid balance

was more negative during the control study than during

the lipid study because of the administration of intrave-

nous fluids during the lipid study, but the differences in

fluid balance were not statistically significant.

Table 1. Metabolic factors during 12 and 84 h of fasting

============

Control study Lipid study

============

Weight loss, kg 2.64±0.13 1.86±0.22*

Measured resting metabolic rate, kcal/kg/day-l 22±l 22±l

Lipid emulsion infused, kcal/kg/day-l 0 23±l

Glycerol infused, g/day 0 19±2

Urinary nitrogen excretion, g/72 h 23.9±3 26.1±3

Fluid balance, ml/72 h -2,761±470 -2,194±133

================

Values are means ± SE.

Fluid balance was fluid intake minus fluid output in urine and estimated

insensible

loss of 800 ml/day.

Significantly different from control value, * P = 0.008.

The plasma substrate and hormone concentrations

after 12 and 84 h of fasting are shown in Table 2.

As expected, plasma glucose and insulin decreased, whereas

total free fatty acids, ketone bodies, and epinephrine

increased after fasting in the control study. Changes in

substrates and hormones were the same in the lipid study

as those during the control study despite the daily infu-

sion of lipid calories. There was no significant change in

plasma norepinephrine after fasting in either the control

or lipid studies. Lipid infusion on the first day of fasting

caused a fourfold increase in plasma triglyceride

concentration. Plasma triglycerides increased from 68±26

mg/dl in the basal state to 278±58 mg/dl at 5 h of

lipid infusion. Basal triglycerides did not change after 84

h of fasting in the control study but increased by -60%

after 84 h of fasting (12 h after stopping the infusion of

Intralipid) in the lipid study. The difference in triglycer-

ide levels in the lipid study, however, were not statisti-

cally significant because of the small sample size and the

variability in the data.

Table 2. Plasma substrate and hormone concentration

=================

Control study Lipid study

12-h fast 84-h fast 12-h fast 84-h fast

=================

Glucose, mg/dl 92±2 68±2* 86±2 66±3*

Free fatty acid, µM 376±92 917±61* 487±66 1,023±80*

Triglyceride, mg/d1 57±lO 61±8 68±26 109±33

Acetoacetate, µM 72±8 1,060±213* 74±ll 980±80*

ß-Hydroxybutyrate, µM 84±20 2,560±370* 108±50 2,540±440*

Insulin, µU/ml 7.5±O.7 2.720.2±6.7k0.7 68+12t 3.2±O.l*

Epinephrine, pg/ml 39±8 68±26† 42±9 70±15†

Norepinephrine, ng/ml 142±21 194±45 179±15 163±25

=================

Values are means ± SE.

For lipid study, 84-h fast was 12 h after stopping lipid emulsion infusion.

Significantly different from corresponding 12-h value, *P < 0.001, †P < 0.01.

Lipolytic rates and the absolute increase in the Ra of

glycerol and palmitic acid during fasting were similar in

both the control and lipid studies (Fig. 1). Glycerol Ra

increased by 1.63±0.42 µmol/kg/min (from 1.94±

0.30 to 3.57±0.21 µmol/kg/min after 12 and 84 h of

total fasting, respectively) in the control study (P <

0.001) and by 1.35±0.41 µmol/kg/min (from 2.28±

0.12 to 3.63±0.41 µmol/kg/min after 12 and 84 h of

fasting plus daily lipid infusions, respectively) in the lipid

study (P <0.001). Palmitic acid Ra increased by 1.41±0.46

µmol/kg/min (from 1.50±0.35 to 2.91±0.23 µmol/kg/min

after 12 and 84 h of total fasting,

respectively) in the control study (P < 0.001) and by 1.43

±0.44 µmol/kg/min (from 1.57±0.23 to 3.01±0.32 -

µmol/kg/min after 12 and 84 h of fasting plus daily

lipid infusions, respectively) in the lipid study (P <

0.001).

Triglyceride oxidation increased during fasting in both

the control and lipid studies (P < 0.001; Fig. 1). Daily

lipid infusion did not affect the rate of triglyceride oxi-

dation, and the values at 12 and 84 h of fasting were

similar in both studies. The rates of triglyceride oxidation

in the control and lipid studies were 1.07±0.09 and 1.13

±0.17 µmol/kg/min, respectively, after 12 h of fast-

ing and 1.77±0.10 and 1.67±0.08 µmol/kg/min,

respectively, after 84 h of fasting. The percentage of

released fatty acids that were oxidized for fuel was also

the same in both studies and remained constant during

fasting. Approximately 50% of mobilized triglycerides

were oxidized after both 12 and 84 h of fasting.

The rate of total triglyceride recycling was similar in

both the control and lipid studies (Fig. 1). Total triglyc-

eride recycling increased from 0.87±0.31 to 1.80±0.23

µmol/kg/min after 12 and 84 h of fasting, respec-

tively, in the control study (P < 0.01) and from 1.15±0.15

to 1.96±0.37 µmol/kg/min, respectively, in the

lipid study (P < 0.01). The rate of intracellular adipocyte

triglyceride recycling was similar in both studies because

the relationship between palmitic acid Ra and glycerol Ra,

an index of intracellular recycling, was similar. The esti-

mated energy cost of total triglyceride recycling was min-

imal and accounted for - 1 and -2% of the daily RMR

after 12 and 84 h of fasting, respectively. ...

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

__________________________________

- PC Magazine Editors' Choice 2005

http://mail.