CR in bed rest

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Hi All,

The pdf-avavailable below appears to suggest that CR helps the function of our

blood

flow through our vascular system and the profile of our blood fats irrespective

of

the requirement for ambulation.

This is important for more than space flight?

J Appl Physiol. 2005 Aug 11; [Epub ahead of print]

Modulation of endothelial and smooth muscle functionby bed rest and

hypoenergetic,

low-fat nutrition.

Hesse C, Siedler H, Luntz SP, Arendt BM, Goerlich R, Fricker R, Heer M, Haefeli

WE.

Prolonged microgravity alters the regulation of the peripheral vasculature. The

influence of reduced food intake, as often observed in astronauts, on vascular

function is unclear. In a randomized, four-phase cross-over study the effect of

simulated microgravity (13 days of bed rest), energetic restriction (-25%, fat

reduced), and their combination on endothelium-dependent and -independent

vasodilation was compared with ambulatory control conditions. Using venous

occlusion

plethysmography cumulative intraarterial dose-response curves to

endotheliumdependent (acetylcholine) and -independent (sodium nitroprusside)

vasodilators were constructed in 10 healthy male volunteers before and on day 13

of

each of the four intervention periods. Bed rest combined with normoenergetic

nutrition impaired the dose-response to acetylcholine (ANOVA, p=0.004) but not

to

sodium nitroprusside, whereas hypoenergetic diet under ambulatory conditions

improved responses to acetylcholine (p=0.044) and sodium nitroprusside

(p<0.001).

When bed rest was combined with hypoenergetic diet acetylcholine responses did

not

change. Similarly, under control conditions no change was observed. Individual

changes in the total cholesterol-to-HDL ratio were correlated with changes in

endothelial and vascular smooth muscle relaxation. In conclusion, short-term bed

rest impairs endothelium-dependent arterial relaxation in humans. A

hypoenergetic,

low-fat diet modulates serum lipids, improves endothelium-dependent and

-independent

relaxation, and may antagonize the unfavorable effects of simulated microgravity

on

endothelial function.

PMID: 16099888

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=16099888 & query_hl=3

.... Table 1 - Effects of bed rest and nutrition on anthropometric, hemodynamic,

and

DNA

strand break variables in 10 healthy participants

........................................

----ambulatory+normoenergetic bed rest+normoenergetic ambulatory+hypoenergetic

bed

rest+hypoenergetic

----Adaptation Intervention Adaptation Intervention Adaptation Intervention

Adaptation Intervention

........................................

Weight [kg] 76.1±9.4 75.8±9.6 76.9±8.7 75.4±9.1** 78.6±11.0 77.1±11.2** 77.9±9.6

75.2±9.5**

BMI [kg/m²] 22.8±3.2 22.7±3.3 23.1±2.9 22.7±3.0** 23.6±3.8 23.2±3.9** 23.4±3.3

22.6±3.3**

Mean BP [mmHg] 71±3 †71±2 68±3 ‡ 75±3 76±3 74±2 76±1 79±2

Heart Rate [1/min] 65±2 † 61±2 63±2 ‡ 60±2 63±1 59±1** 62±2 59±2

FAV [ml] 1465±68 1455±65 1480±68 1465±70 1430±62 1420±65 1400±58 1385±55

FBF [ml/min/100ml] 3.3±0.5 4.5±0.7 4.7±0.7 3.8±0.5 4.3±0.3 3.6±0.3 5.2±1.1

3.6±0.4

AUC SNP [units] 14.2±1.8 14.2±1.4 15.5±1.5 14.6±2.1 12.1±1.1 12.8±1.0 12.6±1.2

11.1±0.9

AUC ACh [units] 22.9±3.2 24.9±3.3 25.5±4.8 19.3±3.6 17.8±3.0 25.5±4.7 21.7±3.5

16.9±4.2

AUC ACh/AUC SNP 1.64±0.18 1.82±0.23 1.63±0.29 1.18±0.34 1.43±0.20 1.93±0.30*

1.72±0.24 1.44±0.29

TM [µm] 2.35±0.18 2.31±0.19 ** 2.16±0.34 2.39±0.22 ** 2.33±0.18 2.12±0.18 **

2.45±0.19 2.51±0.15 **

...................................

Data are from day 9 of the adaptation and from day 13 of the intervention

period.

BMI indicates body mass index; BP blood pressure; FAV forearm volume; FBF

forearm

blood flow; TM tail moment. AUC SNP and AUC ACh indicate the area under the

dose-response-curves of SNP and ACh. Values are means±SE from 10 participants,

with

the following exceptions: † n=9 and ‡ n=8 participants (missing data due to

hard

disc failure), ** n=8 subjects (missing data due to gel damage during storage).

*p<0.05, ** p<0.01 for comparison intervention versus respective adaptation

period.

Data of the four adaptation phases were not significantly different.

.... Table 2 - Relative changes in serum lipids after 13 days of intervention

...............................

----ambulatory+normoenergetic bed rest+normoenergetic ambulatory+hypoenergetic

bed

rest+hypoenergetic

................................

delta-Triglycerides [%] -4±7 +4±13 -10±5 -4±4

delta-Total cholesterol [%] -5±2 -9±6 -12±3** -12±3*

delta-HDL [%] -9±2** -14±4* -15±3** -17±3**

delta-LDL [%] -4±4 -2±13 -13±4* -8±5

delta-Total cholesterol/HDL [%] +5±2 +7±9 +5±4 +7±3

..................................

Relative changes in serum lipids from day 9 of the adaptation to day 13 of the

intervention period. Values are means±SE from 10 subjects. *p<0.05, **p<0.01 for

comparison intervention versus corresponding adaptation period.

Table 3 - Correlation between changes in serum lipids, oxidative DNA damage, and

vascular responsiveness in 10 healthy participants

----delta-AUCSNP delta-AUCACh delta-TM [%]

----p-value rs p-value rs p-value rs

...................................

delta-Total cholesterol [%] p=0.01 -0.559 n.s. — n.s. —

delta-HDL [%] n.s. — n.s. — n.s. —

delta-LDL [%] p<0.001 -0.693 n.s. — p=0.04 0.534

delta-Total cholesterol/HDL [%] p=0.008 -0.573 p=0.023 -0.504 n.s. —

delta-TM [%] p=0.003 -0.711 n.s. — — —

......................................

Correlation between percent changes in lipids, percent changes in DNA strand

breaks

and unit changes in the area under the dose-response curves (AUC) of sodium

nitroprusside (SNP) and acetylcholine (ACh) during the hypoenergetic study

phases.

rs=Spearman correlation coefficient.

.... DISCUSSION

.... Effect of a hypoenergetic, low fat diet

The second major finding of the present study was that a short-term low-fat,

hypoenergetic diet

improved vascular smooth muscle function (Figure 2c) as well as endothelial

function

(Figure 3c)

in ambulatory healthy volunteers in the absence of cardiovascular risk factors.

As expected, the low-fat diet induced significant reductions in serum lipids

(Table

2). The

individual changes in LDL were correlated with individual changes in oxidative

stress and

vascular smooth muscle relaxation (Table 3). However, presumably because of the

small

number of participants, a significant correlation with individual changes in

endothelial function

was only found for the parameter cholesterol-to-HDL ratio (Figure 4).

To our knowledge no study has so far investigated dietary approaches to lower

serum

lipids and

their effects on endothelial function in healthy, lean individuals. In a recent

study in

hypercholesterolemic patients monounsaturated fat was substituted by walnuts.

Similarly to our

study, endothelium-dependent vasodilation improved, with changes in vasodilation

being

inversely correlated to changes in cholesterol-to-HDL ratios (32). The effect of

the

walnut diet

may be mediated in part through the improved lipid profile, but special

components

of walnuts

such as á -linolenic acid, L-arginine, and antioxidants might have contributed

to the beneficial

effects (32). Another study in hypercholesterolemic patients (36) investigated

the

effects of LDL

apheresis on vascular function: A single session of LDL apheresis decreases LDL

and

augments

endothelial function and NOx production. Endothelium-independent vasodilation

after

LDL-

apheresis was unchanged (36). However, this is not in contrast with our data,

because the

highest SNP dose infused in this earlier study corresponds to the third dose

used in

our study.

Differences in SNP response were only evident with higher doses and thus may

have

been

missed in this earlier trial. Our finding of augmented endothelium-independent

vasodilator

responses are consistent with a study investigating the relationship between

cardiovascular risk

factors and vascular drug responses (8), that found that a lower

cholesterol-to-HDL

ratio is

associated with enhanced responses to both NO donors and ACh. It is possible

that

decreased

endothelin-1 may contribute to improved vasodilator function. However,

endothelin-1

increases

after acute LDL lowering (36) and thus would augment vascular tone and impair

SNP

responses,

which was not the case.

The strong correlations between changes in ACh responses after LDL apheresis and

respective

changes in LDL, oxidized LDL, and NOx production (36) as well as the finding

that

LDL

increases vascular production of superoxide anion, which can inactivate NO

rapidly

(28),

suggest that improvement of endothelial function after LDL lowering may be

caused by

augmented NO bioavailability due to reduction in oxidative stress (36). Indeed

the

individual

decrease in LDL values in our study was correlated with the reduction of

oxidative

stress as

assessed by DNA strand breaks (expressed as TM). A recent study in rabbits has

confirmed that

this parameter is not only associated with cholesterol-induced atherosclerotic

plaque formation,

but also decreases quickly after cholesterol withdrawal (24).

Epidemiologic and angiographic studies have firmly established a causal relation

between

elevated serum cholesterol levels and the development of atherosclerosis and

ischemic heart

disease (23). Furthermore, the results of primary- and secondary-prevention

trials

provide

compelling evidence that cholesterol reduction leads to a significant

improvement of

endothelial

vasomotor function and a decrease in the rate of cardiovascular events (23). Our

study expands

this knowledge in so far, that even in healthy humans without any cardiovascular

risk factors

only 13 days of a moderate hypoenergetic, low fat diet – independent of

confounding

factors

such as co-medication or physical activity – result in a substantial increase in

vasodilator

function along with the expected decrease of serum lipids.

Combined effect of bed rest and hypoenergetic diet

When bed rest was combined with hypoenergetic diet, endothelium-dependent

vasodilation was

still lower at all ACh dose-rates (Figure 3d), but it was less pronounced than

the

effect of

normoenergetic bed rest and did not reach statistical significance. These data

may

therefore

indicate that a hypoenergetic, low fat diet may antagonize the unfavorable

effects

of bed rest on

endothelial function, possibly by partially restoring NO bioavailability.

Unfortunately our study design does not allow quantification of the extent of

improvement

properly. Although the standardisation within a study session (comparison before

and

after

intervention) was high, comparison between study sessions is less exact due to

relatively long

periods between study sessions, and the change of infusion arm between sessions.

In summary, strict bed rest for 13 days impairs endothelium-dependent arterial

relaxation in

healthy males. This effect was offset by a concurrent low fat diet, which

modulates

serum lipids

and oxidative stress, and improves endothelium-dependent and -independent

vasodilation.

Because endothelial dysfunction predicts the occurrence of cardiovascular

disease

(16) and is

independently related to future cardiovascular events (12), protective effects

of a

low fat diet (or

other nutritional or pharmacological interventions) on endothelial function are

worth being

investigated in astronauts and bedridden patients in future studies.

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

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