Intermittent fasting for heart risk

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Hi All,

The pdf-available not in Medline yet paper below seems to support the view that

it

would be good to intermittently fast for our heart health. Body weights seemed

not

to be affected by the Muslin fasting month study.

Effects of Intermittent Fasting on Serum Lipid Levels, Coagulation Status and

Plasma Homocysteine Levels.

Benli Aksungar, Fehime; Eren, Aynur; Ure, Sengul; Teskin, Onder; Ates,

Gursel.

ls of Nutrition & Metabolism, Mar/Apr2005, Vol. 49 Issue 2, p77, 6p

Abstract: Background: During Ramadan, Muslims fast during the daylight hours

for a

month. The duration of restricted food and beverage intake is approximately 12

h/day

which makes Ramadan a unique model of intermittent fasting. Many physiological

and

psychological changes are observed during Ramadan that are probably due to the

changes in eating and sleeping patterns. Methods: Serum total cholesterol,

triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL),

prothrombin time, activated partial thromboplastin time (aPTT), plasma

fibrinogen,

D-dimer and homocysteine levels were measured in 24 healthy fasting volunteers

(12

females, 12 males) aged 21–35 years. Venous blood samples were taken 1 week

before

Ramadan, on the 21st day of Ramadan and 20 days after Ramadan. Results: No

significant changes were observed on serum total cholesterol, triglycerides and

LDL

levels. HDL levels were significantly elevated during Ramadan (p < 0.001) and 20

days after Ramadan (p < 0.05). Prothrombin time, aPTT, fibrinogen and D-dimer

levels were in the physiologic limits in all samples but D-dimer levels were

significantly low at the end of Ramadan in comparison to pre- and post-fasting

levels (p < 0.001). Homocysteine levels, being still in reference ranges, were

low

during Ramadan (p < 0.05) and reached the pre-fasting levels after Ramadan.

Conclusion: Our results demonstrate that intermittent fasting led to some

beneficial

changes in serum HDL and plasma homocysteine levels, and the coagulation

status.

These changes may be due to omitting at least one meal when the body was

particularly metabolically active and possibly had a low blood viscosity level

at

the same time. We conclude that intermittent fasting may have beneficial effects

on

hemostatic risk markers for cardiovascular diseases.

Introduction

It is well known that nutritional habits, sleeping pat-

terns and frequency of meals have profound effects on

maintaininghumanhealth.Ramadan isareligiousmonth

during which all Muslims refrain from eating and drink-

ing during the daylight hours for a month.The duration

of restricted food and beverage intake is approximately

12 h/day which makes Ramadan a unique model of in-

termittent fasting.Many physiological and psychological

changes that are probably due to the changes in eating

and sleeping patterns are observed during Ramadan [1,

2].

Homocysteine is a mixed amino acid, intermediary on

the metabolic pathway between methionine and cysteine.

Several B vitamins are cofactors in the methionine cata-

bolic pathway.Deficiencies in folic acid, vitamin B 12 and

pyridoxine have been associated with mildly elevated ho-

mocysteine levels in healthy populations [3, 4].The role

of plasma homocysteine levels in vascular diseases and

the mechanisms are still a matter of debate.Recent stud-

ies suggest that hyperhomocysteinemia may stimulate

procoagulant factors or impair anticoagulant mecha-

nisms by affecting normal endothelial functions [4].

Circulating concentrations of D-dimer reffect the ex-

tent of & #64257; brin turnover in the circulation as this antigen is

present in several degradation products from the cleavage

of cross-linked & #64257; brin by plasmin [5, 6].Hence, plasma D -

dimer levels indicate & #64257; brin generation and & #64257; brinolytic

activity in the body.It has been shown that & #64257; brin D-dimer

is associated with the risk of future ischemic heart disease

in individuals with and without baseline evidence of vas-

cular disease [6–8].

Physiological changes during prolonged intermittent

fasting and the possible effects of delayed or shortened

periods of sleep on human metabolism are not well estab-

lished.In this study we have investigated the effects of

intermittent fasting and the change in sleeping pattern on

serum lipid levels, coagulation status and plasma homo-

cysteine levels.

.... during Ramadan, total energy intake was increased minimally (2, 180 vs.2,

320

kcal during

Ramadan)which is probably because of increased carbohydrate

intake (approximately 49.7 vs.53.6%during Ramadan).

During Ramadan the frequency of meals was reduced to two,

compared to three times in the pre-and post-fasting period.

.... Results

No significant changes were observed on serum total

protein, albumin, calcium, TG and LDL levels.HDL lev-

els were significantly elevated during Ramadan (p !

0.001)and 20 days after Ramadan (p !0.05).The mean

HDL risk factor was decreased during Ramadan (p !

0.05)and remained depleted after Ramadan fasting for

at least 20 days (p !0.05).PT, aPTT, fibrinogen and D-

dimer levels were in the physiologic limits in all samples

but D-dimer levels were significantly low at the end of

Ramadan in comparison to pre-and post-fasting levels

(p !0.001).

Homocysteine levels, being still in reference ranges,

were low during Ramadan and reached the basal levels,

(pre-fasting levels)after Ramadan.D-dimer levels and

homocysteine levels were positively correlated (r =0.67),

while fibrinogen and D-dimer levels were not correlated

(r =0.08).Average body weight and 24-hour urinary vol-

umes did not change significantly.The mean±SD values

of all parameters of male subjects are shown in table 1

and of female subjects in table 2 .

Table 1. Intermittent fasting data of male subjects:fasting and post-fasting

levels

are compared to basal (pre-fasting)levels

--------------------------

Pre-fasting Fasting Post-fasting

Cholesterol, mg/dl 179.25±47.94 174.11±42.73 178.8±39.68

LDL, mg/dl 115.7±37.44 109.8±34.85 106.1±35.17

HDL, mg/dl 49±15.25 56±16.31**57±15.09**

Triglycerides, mg/dl 76.27±29.04 76.68±27.08 70.05±27.8

HDL risk factor 3.85±1.41 2.92±1.12*2.97±1.33*

BUN, mg/dl 17±2.51 18±3.52 17±2.12

Creatinine, mg/dl 1.0±0.1 1.1±0.12 1.0±0.08

Total protein, g/l 7.8±1.32 7.9±1.23 7.7±1.28

Calcium, mg/dl 9.01±0.5 9.41±0.23 9.46±0.33

D-dimer, ng/ml 159.3±21.6 89.2±27.7**144.2±11.6

Fibrinogen, mg/dl 255±42 286±56 278±48

PT, s 12.50±1.10 12.12±1.02 12.46±0.91

aPTT, s 32±3.2 33±2.15 33±2.9

Homocysteine, µM l 10.20±1.26 9.06±1.22*9.52±1.03

Urine volume, ml/24 h 1, 750±198 1, 790±145 1, 830±142

Weight, kg 82.24±5.47 82.47±6.05 82.41±5.21

Values are mean±SD.

*p <0.05, **p <0.001.

Table 2. Intermittent fasting data of female subjects:fasting and post-fasting

levels are compared to basal (pre-fasting) levels

----------------------------

----Pre-fasting Fasting Post-fasting

-------------------------------

Cholesterol, mg/dl 178.15±67.73 182.32±58.94 176.91±79.65

LDL, mg/dl 107.4±37.44 103.7±54.67 99.4±64.89

HDL, mg/dl 57.4±13.63 66.5±11.79**66.9±11.08**

Triglycerides, mg/dl 66.82±23.53 68.66±15.49 65.58±26.74

HDL risk factor 3.31±1.23 2.63±1.02*2.71±1.47*

BUN, mg/dl 15±1.46 14±2.67 15±2.71

Creatinine, mg/dl 0.9±0.14 1.0±0.24 0.9±0.18

Total protein, g/l 7.3±0.38 7.5±0.23 7.4±0.38

Calcium, mg/dl 8.9±1.40 9.1±1.37 9.5±1.46

D-dimer, ng/ml 167.3±35.2 73.5±26.7**153.7±28.4

Fibrinogen, mg/dl 258±67 266±43 262±76

PT, s 13.15±1.42 13.27±1.89 13.52±1.72

aPTT, s 33±2.66 34±1.75 32±2.41

Homocysteine, µM l 10.77±2.58 8.52±1.78**9.97±2.15

Urine volume, ml/24 h 1, 640±178 1, 580±239 1, 690±216

Weight, kg 63.14±6.22 62.69±5.92 62.23±6.67

---------------------------------

Values are mean±SD.

*p <0.05, **p <0.001.

Discussion

Long-lasting modi & #64257; cations in the circadian distribu-

tion of the eating and sleeping schedule result in various

changes in metabolism and Ramadan fasting is shown to

have an impact on metabolic endocrine processes [9, 10].

In the present study our subjects had the same working

hours before and during Ramadan.According to the

questionnaire, their sleep was delayed 2 h on average.

There were two major changes in their routine:meal tim-

ing and sleep schedule.The lack of significant change in

body weight indicates that food intake from sunset to

sunrise was suf & #64257; cient to maintain energy balance.On the

other hand, during the daylight hours, fasting subjects

must certainly be undergoing dehydration [11], but as

con & #64257; rmed from the body weight and the questionnaire,

there was no chronic hypohydration during Ramadan

among our subjects.The water balance seemed to be con-

stant on a daily basis as the 24-hour urinary volumes did

not change significantly.Consistent with our study, in

another recent study using an isotopic tracer technique,

it has been demonstrated that total body water content

was conserved during Ramadan fasting [12].

Recent studies with human beings and animals with

mild hyperhomocysteinemia provided an understanding

of the mechanism that underlies between mild elevations

of homocysteine and vascular disease.These studies dem-

onstrated the possibility that the effect of elevated homo-

cysteine is multifactorial, affecting both the vascular wall

structure and blood coagulation system [3, 13].A meta-

analysis by the Homocysteine Studies Collaboration con-

& #64257; rmed homocysteine as a risk factor for the & #64257; rst events

of stroke and coronary heart disease (CHD)[14].Our re-

sults demonstrate that homocysteine levels were de-

creased in the last week of Ramadan and returned almost

to the basal values 20 days after Ramadan.None of our

subjects used any kind of vitamin supplements and ac-

cording to the questionnaire, consumption of food con-

taining folic acid and other B vitamins did not change

signi & #64257; cantly during the study period.The changes in the

rest-activity cycle and sleep and food patterns during

Ramadan may bene & #64257; cially affect the bioavailabilities or

redistribution of cofactors such as B vitamins.However,

mechanisms that underlie homocysteine decrease during

intermittent fasting for 15 h/day for a month, as in the

Ramadan fasting model, must be further investigated as

some previous studies reported mild hyperhomocystein-

emia under fasting conditions due to mild impairment in

the methylation pathway, although in these studies the

fasting conditions were different [3, 15].

In the present study there was a significant decrease in

D-dimer levels during fasting.It has been suggested that

modestly elevated circulating D-dimer levels reffect mi-

nor increases in blood coagulation, thrombin formation

and a turnover of cross-linked intravascular & #64257; brin which

is partly intra-arterial in origin [5, 6].These increases may

be relevant to CHD as previous prospective studies sug-

gest that CHD risk is approximately 70%greater in those

having higher plasma D-dimer levels [5, 16, 17].Aybak

et al.[18] showed that Ramadan fasting led to a decrease

in the platelet responses to different aggregating agents.

On the other hand, an increase in bleeding and coagula-

tion time (but not above the physiologic limits)had been

shown by the same study.These results are in agreement

with the present study.In addition, plasma factor VII co-

agulant activity (FVIIc)is demonstrated to be raised post-

prandially and remained elevated 7 h, especially follow-

ing high-fat diets [19].During Ramadan fasting at least

one meal is omitted, hence a possible increase in FVIIc

activity after lunch may not be seen.Moreover, associa-

tions between homocysteine and & #64257; brin D-dimer are un-

der investigation in recent studies, while in multivariate

analysis the association of homocysteine and D-dimer is

demonstrated to remain statistically significant after ad-

justment for indicators of chronic in & #64258; ammation and & #64257; -

brinogen [20, 21].These results are consistent with our

study in which we showed a significant decrease in D -di-

mer levels indicating & #64257; brin generation in the body was

decreased during intermittent fasting.Additionally, ho-

mocysteine levels were correlated with D-dimer levels.In

combination with other as yet undetermined mecha-

nisms, such as increased HDL levels, coagulation activa-

tion may be minimal during prolonged intermittent fast-

ing.

Plasma fibrinogen and D-dimer levels were not corre-

lated in our study.Previous studies have reported mini-

mal correlations between plasma D-dimer and fibrinogen

levels.This lack of correlation has been reported to have

little reduction in the strength of association between high

D-dimer levels and CHD, indicating that D-dimer is an

independent risk factor for CHD [16, 22, 23].On the

other hand, we have measured clottable fibrinogen.Sweet-

nam et al.[24] reported that a heat-precipitation nephelo-

metric assay of fibrinogen has a better performance in

minimal variations and predicting CHD.To our knowl-

edge, no other reports on plasma D-dimer, fibrinogen and

homocysteine levels during Ramadan fasting are avail-

able.

Most of the previous studies on Ramadan fasting did

not use female subjects – in the present study however, ,

both female and male subjects were studied.The interdic-

tion of fasting during the menstrual period (5±2 days)

seems to be without effect, as the data from female sub-

jects is similar to that from male subjects.Previous stud-

ies showed that at least 10 days were necessary for the

body to adapt metabolically to the changes in feeding and

sleeping habits [1, 10].Moreover, it has been shown that

metabolic changes remain the same for at least 10 days

after Ramadan [1, 10].In the present study, 5±2 days

were possibly not enough for the metabolic shift and that

may be the reason for the interruption of fasting during

the menstrual period, not affecting our data.

In our study, serum HDL levels were significantly el-

evated and HDL risk factor was significantly decreased

during Ramadan and remained the same 20 days after

Ramadan in both female and male subjects.The change

in eating habits during Ramadan did not affect other li-

poproteins, TC and TG levels.These results are consis-

tent with the previous study by Adlouni et al.[1].How-

ever, in their studies, Maislos et al.[25, 26] reported that

HDL levels returned to basal values 4 weeks after the end

of Ramadan.In our subjects, 20 days after Ramadan may

not be enough for HDL to return to pre-fasting levels

which seems to be an advantage on the risk of CHD.The

principle role of HDL in lipid metabolism is the uptake

and transport of cholesterol from peripheral tissues to the

liver through a process known as reverse cholesterol trans-

port which is proposed as a cardioprotective mechanism.

Low HDL levels are associated with an increased risk of

CHD [27].On multivariate analysis it has been suggested

that the best independent lipid predictor of CHD risk

among populations is the TC/HDL ratio (HDL risk fac-

tor)[28, 29] and a unit increment of HDL risk factor adds

an excess of 68%to both the non-fatal and fatal CHD

event risk [28, 30].

In the study, non-fasting samples were taken in the

morning and the fasting ones in the afternoon.This point

is a limitation for the present study as some compared

parameters have circadian variations.However, homo-

cysteine, D-dimer, PT, aPTT, BUN, creatinine and total

protein levels do not intend to change during the day.

Another limitation for the study is only one measurement

for the D-dimer levels at the end of the fasting period was

made.In order to exclude a systematic error, additional

series of D-dimer measurements could have been done.

However, our results demonstrate that although no nu-

tritional diet regimen and no reduction in caloric intake

were applied to the subjects, intermittent fasting led to

some bene & #64257; cial changes in serum HDL and homocyste-

ine levels, and in the coagulation status.These changes

may be due to omitting at least one meal when the body

was particularly metabolically active and possibly had a

low blood viscosity level at the same time.We conclude

that intermittent fasting may have bene & #64257; cial effects on

hemostatic risk markers for cardiovascular diseases.

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

__________________________________

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