Re: Intermittent fasting for heart risk

[Guest guest]

Hi Al:

I can't wait to see the results of the 'eating once a day in the

early evening' study (Mattson I think?). They should be available

soon. Based on the results below it seems likely that a '23-hour-

fast' regimen will be beneficial also.

Can anyone please tell me about the significance of the 'D-dimer'

biomarkers in the study below? TIA.

Rodney.

--- In , Al Pater <old542000@y...>

wrote:

> 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@y...

>

>

>

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