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The effect of intermittent fasting on blood pressure variability in patients with newly diagnosed hypertension or prehypertension

Yunus Erdem, Gülsüm Özkan, Şükrü Ulusoy, Mustafa Arıcı, Ülver Derici, Şule Şengül, Şükrü Sindel, Şehsuvar Ertürk

PII: S1933-1711(17)30412-6

DOI: 10.1016/j.jash.2017.11.008

Reference: JASH 1102

To appear in: Journal of the American Society of Hypertension

Received Date: 13 August 2017

Revised Date: 8 November 2017

Accepted Date: 22 November 2017

Please cite this article as: Erdem Y, Özkan G, Ulusoy Ş, Arıcı M, Derici Ü, Şengül Ş, Sindel Ş, Ertürk Ş, Turkish Society of Hypertension and Renal Diseases, The effect of intermittent fasting on blood pressure variability in patients with newly diagnosed hypertension or prehypertension, Journal of the American Society of Hypertension (2018), doi: 10.1016/j.jash.2017.11.008.

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ACCEPTED MANUSCRIPT The effect of intermittent fasting on blood pressure variability in patients with newly

diagnosed hypertension or prehypertension

Yunus Erdem1, Gülsüm Özkan2, Şükrü Ulusoy3, Mustafa Arıcı1, Ülver Derici4, Şule Şengül5,

Şükrü Sindel4, Şehsuvar Ertürk5; Turkish Society of Hypertension and Renal Diseases

Department of Nephrology1, Hacettepe University, School of Medicine, Ankara, Turkey

Department of Nephrology2, Namık Kemal University, School of Medicine, Tekirdağ, Turkey

Department of Nephrology3, Karadeniz Technical University, School of Medicine, Trabzon,

Turkey

Department of Nephrology4, Gazi University, School of Medicine, Ankara, Turkey

Department of Nephrology5, Ankara University, School of Medicine, Ankara, Turkey

Running title: Fasting and Blood Pressure Variability

Corresponding Author: Dr. Gülsüm ÖZKAN

Namık Kemal University

School of Medicine

Department of Nephrology

59000 Tekirdağ

TURKEY

Mail- address : [email protected]

Phone number : +90 284 2507359

This study has not been presented previously

Conflict of Interest: We report no conflict of interest

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ACCEPTED MANUSCRIPT Abstract

Background: Intermittent fasting is a phenomenon which can be observed in most humans.

The effect of intermittent fasting on blood pressure variability (BPV) has not previously been

investigated. The purpose of this study was to assess the effect of fasting on BP (with office,

home, central and ambulatory blood pressure monitoring [ABPM]) and on BPV.

Methods: Sixty individuals were included in the study. Office, home, ABPM and central BP

measurements were performed before and during intermittent fasting. Standard deviation (SD)

and coefficient variation (CV) were used for office and home BPV measurement, while the

smoothness index (SI) was used to calculate ABPM variability. Patients’ BP and BPV values

before and during intermittent fasting were then compared.

Results: Intermittent fasting resulted in a significant decrease in office BP values and ABPM

measurements but caused no significant change in home and central BP measurements.

Twenty-four hour urinary sodium excretion decreased. SI values obtained from ABPM

measurements were low, in other words, BPV was greater. BPV was higher in patients who

woke up to eat before sunrise, but BPV was low in patients with high BMI.

Conclusion: Intermittent fasting produced a significant decrease in BP values in terms of

office and ABPM measurements in this study, but caused no significant change in central BP

and home measurements. We also identified an increase in BPV during intermittent fasting,

particularly in patients who rose before sunrise.

Key words: Fasting, intermittent fasting, blood pressure variability, BPV, central blood

pressure

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ACCEPTED MANUSCRIPT Introduction:

Various types of fasting have been performed since ancient times, for reasons of both health

benefits and of religious belief. Intermittent fasting is a religious obligation performed by

many believers worldwide. It generally involves consuming no food or drink, broadly from

before sunrise to sunset. In addition, in order to prepare themselves for hunger and thirst

throughout the day, people who fast often wake up before sunrise, have an early meal (sahur),

and then go back to sleep. Other individuals who fast may forego the sahur. Intermittent

fasting therefore results in temporary changes to the individual’s familiar patterns of sleep and

eating.

While the effect on human health of intermittent fasting is uncertain, previous studies have

shown that it may have potentially beneficial effects in the prevention and treatment of

diseases such as obesity, type 2 diabetes mellitus and cardiovascular diseases [1,2]. Previous

animal studies have shown that blood pressure (BP) falls during the fasting period, and then

increases again after eating [3]. Very few clinical studies have investigated the effects of

intermittent fasting on BP control and course in hypertensive patients. One such study was

performed by Perk G et al., who determined no change before and after intermittent fasting in

ambulatory blood pressure monitoring (ABPM) of hypertensive patients under treatment [4].

Ural et al. investigated the course of BP before and after intermittent fasting in stage 2-3

hypertensive patients receiving combination treatment, and also determined no difference [5].

However, apart from a very few studies of hypertensive patients, no studies have investigated

the effects of intermittent fasting on blood pressure variability (BPV) and urinary sodium

excretion in pre-hypertensive and/or newly diagnosed hypertensive patients.

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ACCEPTED MANUSCRIPT The purpose of this study was to assess the effects of intermittent fasting on BPV, central BP

and urinary sodium excretion in pre-hypertensive and/or newly diagnosed hypertensive

patients.

Materials-Methods

Cappadocia cohort

This is a prospective cohort study conducted by Turkey Society of Internal Medicine (TSIM)

[6]. The observational part of the study began in March 2013. Once informed written consent

had been obtained, participants were administered a questionnaire to collect baseline data.

Study personnel collected the following information from participants while administering a

167-question electronic questionnaire: demographic characteristics, place of residence, level

of education, employment status, lifestyle information, and medical history, including

diagnosed illnesses and medication use. Physical examinations were performed on all

subjects, including the measurement of blood pressure (at least twice), body weight, height,

and waist and neck circumferences. The study participants survey every year in terms of

changes in these factors, the development of new illnesses, changes in weight, waist size, and

medication use, level of physical activity, smoking status, alcohol consumption, and

nutritional factors.

Patient selection

Individuals followed-up due to prehypertension and hypertension in the Cappadocia cohort

and living in Gülşehir, aged 18 or over, who had been informed about the study and gave

verbal agreement to participate, with a sufficient intellectual level to provide a medical

history, to measure BP at home and to perform 24-h ABPM and who fasted intermittently

were included in the study. Pregnant subjects, patients with known heart failure, kidney

failure or chronic liver disease, subjects using antihypertensive drugs, who had fasted in the

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ACCEPTED MANUSCRIPT previous 24 h before their visit and subjects who were unwilling to provide contact details

were excluded. Ethical committee approval for the study was obtained from the Hacettepe

University Medical Faculty, and the study began once informed written consent had been

received from patients.

Study protocol:

Individuals from the Cappadocia cohort diagnosed with prehypertension and hypertension

(SBP 120-139 and ≥140; DBP 80-89 and ≥90 mmHg) according to the JNC 8 guideline [7],

under monitoring and wishing to be included in the study underwent a detailed physical

examination. Those subjects who did not use antihypertensive agents were included in the

study. Office BP, central BP, and home BP measurement and 24-h ABPM and 24-h urine

collection procedures were then repeated before and during the intermittent fasting period,

after subjects had fasted for at least one week, using the protocol and equipment described

below.

Office blood pressure measurement

Office BP measurements were performed with a UA-651SL monitor (Kitamoto-shi, Saitama

364-8585 Japan). Before office BP measurement, the patient was left for at least 5 min in a

relaxed position in a silent room at a suitable temperature. Patients were asked whether they

had used caffeine, alcohol or cigarettes in the previous 1-2 hours. BP was measured from both

arms using an appropriately sized cuff on the forearm, with the forearm at heart level, with the

back and the forearm supported and the patient in a seated position. Care was taken during BP

measurement to ensure that patients did not cross their legs or speak. BP was measured five

times at 1-min intervals. The first measurement was not included in the analysis. The mean of

the subsequent four values was taken and recorded as office BP. Office measurements were

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ACCEPTED MANUSCRIPT performed twice, before and during the intermittent fasting period, after subjects had fasted

for at least one week.

Home blood pressure measurement

Home BP was measured with a UA-651SL (Kitamoto-shi, Saitama 364-8585 Japan) device.

Home BP measurements were performed by patients following appropriate training in the

technique. BP was measured five times at 1-min intervals in the morning and evening for one

week. At the end of one week, mean morning and evening values were taken and recorded as

home BP values. Home BP was measured twice, once before and once during the intermittent

fasting period, after subjects had fasted for at least one week.

Ambulatory blood pressure measurement

Twenty-four hour BP (24-h ABPM) was measured twice, once before and once during the

intermittent fasting period, after subjects had fasted for at least one week, using a Mobil-O-

Graph NG 24h ABPM Classic (I.E.M. GmbH, Stolberg, Germany) device. Both monitoring

periods began at approximately the same time. Monitoring was performed from the non-

dominant arm. Patients were asked to record their hours of sleeping, waking and eating and

their daily activities. Sleeping-waking periods were evaluated accordingly. Patients were

instructed to keep the relevant arm immobile during BP measurement. Daytime BP

measurement was performed once every 15 min and night-time measurement once every half

hour. Measurements with at least 70% validity from day and night-time measurements in 24-h

ABPM records were included for analysis.

Central blood pressure measurement

Central BP was measured using the ARCSolver method. The ARCSolver method is

commercially available in the oscillometric Mobil-O-Graph NGW 24-hour ambulatory BP

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ACCEPTED MANUSCRIPT and PWA monitor (IEM; Stolberg, Germany). The device is approved by the Food and Drug

Administration and by Conformité Européenne, and its blood pressure detection unit has been

validated according to British Hypertension Society [8] and European Society of

Hypertension [9] recommendations. The algorithms for the generation of central SBP and

aortic blood pressure curves, using the oscillometric method, have been reported previously

[10] but are briefly explained here. Following conventional oscillometric BP assessment,

peripheral pressure waves are recorded, using the brachial cuff, at the DBP level for 10

seconds. Following digitization, a 3-step algorithm is applied. First, the single pressure waves

are verified for their plausibility by testing minima position and corresponding wavelengths.

Minima are detected by means of an iterative procedure evaluating higher order time

derivatives of the pressure signal. The second stage involves comparison of all single pressure

waves with one another to recognize artifacts. Aortic pulse waves are then generated via a

general transfer function. Modulus and phase characteristics of the ARCSolver transfer

function are available [10]. Finally, the coherence of the measured parameters is verified and

displayed within the Mobil-O-Graph NG software package which also allows visual

inspection to reveal consistently recorded intrinsic waveform distortion manually. The entire

process takes between 2 and 3 minutes.

24-h urine collection

Patients were asked to collect 24-h urine; they were instructed not to save the urine from their

first urination on the morning when collection began, but to urinate into a collection container

every time thereafter, including the first urination the following morning, and then to bring all

collected urine to the laboratory. Urine sodium was measured in patients’ 24-h urine via the

enzymatic colorimetric method using a Hitachi Modular P800 (Roche Diagnostic Corp.

Indiana, USA) autoanalyzer. The 24-h sodium excretion value (mmol/d) for each individual

was calculated as the concentration of sodium in the urine (mmol/L) × urinary volume (L/d).

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ACCEPTED MANUSCRIPT Twenty-four hour urine was collected twice, once before and once during the intermittent

fasting period, after subjects had fasted for at least one week.

Blood pressure variability analyses

Standard deviation (SD) and coefficient variation (CV) (SD/mean) for SBP, DBP and heart

rate in the calculation of BPV of office and home BP measurements were calculated

separately. SBP, DBP and heart rate were also calculated separately using the smoothness

index formula (SI) for BPV from ABPM records. Hourly average BP measurements over 24 h

(at 15-min intervals by day and 30-min at night) and SD were recorded for each patient. ∆H

was obtained based on mean BP at the time interval when ABPM was started, with the

difference between mean BP at every subsequent time interval and mean BP at the initial hour

being taken, and total BP differences at each time interval being divided by the total number

of hours over which measurement was performed. Similarly, SD was obtained based on mean

SD at the time interval when ABPM was started, with the difference between mean SD at

every subsequent time interval and mean SD at the initial hour being taken, and total SD

differences at each time interval being divided by the total number of hours over which

measurement was performed.

Statistical analysis

PASW 18.0 for Windows software was used for statistical analysis. Compatibility with

normal distribution of variables was examined using the Kolmogorov-Smirnov and Shapiro-

Wilks tests. Normally distributed data were analyzed using the paired t test, or using the

Wilcoxon Signed Rank test if normality was not established. Correlation analyses were

performed using Pearson and Spearman analyses. Type-1 error levels below 0.05 were

interpreted as statistically significant.

Results

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ACCEPTED MANUSCRIPT Sixty patients were included in the study. The median age of the subjects was 46.77 years, and

61.7% were female. Of these patients, 51.7% rose for sahur. Mean BMI of the patient group

was 30.35±5.87. Mean BMI of the patients who rose for sahur was 30.73±5.01, compared to

29.94± 6.78 for those who did not perform sahur. The difference was not significant. A

significant decrease occurred during intermittent fasting, compared to pre- intermittent fasting

values, in office SBP, DBP and heart rate (p <0.001, 0.039 and 0.003, respectively). No

significant difference was observed in home BP before and during intermittent fasting. When

ABPM measurements before and during intermittent fasting were compared, no significant

difference was observed in all-day and day-time SBP, DBP, MAP or heart rate values, while

DBP, MAP and heart rate values among night-time ABPM data were significantly lower

compared to pre- intermittent fasting values (p values 0.003, 0.025 and 0.012, respectively).

Urinary sodium excretion and urinary volume in the intermittent fasting period were

significantly lower compared to pre- intermittent fasting values (p 0.004 and 0.016,

respectively) (Table 1). Central SBP and DBP in the pre-intermittent fasting period were

112.5 (85-151) and 76.5 (60-109) mmHg respectively, compared to 112 (85-161) and 79.5

(61-112) mmHg in the intermittent fasting period, the difference being statistically significant.

Examination of BPV parameter values before and during intermittent fasting revealed no

significant difference in CV and SD, with which we assessed office BP and home

measurements. ABPM data for 41 of the 60 patients in the study were included in the analysis

(the others were excluded for reasons such as insufficient measurement or no second ABPM

measurement being performed). We used SI to determine the variability of ABPM

measurements before and during intermittent fasting. Briefly, a numerically large SI

calculated using the formula ∆H/SD indicates low variability. SI SBP, SI DBP and SI heart

rate were significantly lower during intermittent fasting than before (p 0.012, 0.005 and 0.002,

respectively) (Figure 1 a,b,c).

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ACCEPTED MANUSCRIPT We assessed parameters affecting BPV individually both before and during intermittent

fasting. Age, sex, urinary sodium excretion and BMI before intermittent fasting had no effect

on variability obtained with office, home and ABPM measurements. There was no significant

relation between age, sex, urinary sodium excretion or BMI and office BPV during the

intermittent fasting period. While no home measurement parameters significantly affected

BPV, SI SBP obtained from ABPM measurements was positively correlated with BMI (r:

0.597, p= 0.003). In other words, the BPVs of patient with greater BMI were lower in the

intermittent fasting period. Sahur caused no change in home BPV, although office CV SBP

and SD SBP among individuals who did rise for sahur were significantly higher compared to

those who did not (p 0.047 and 0.0.29, significantly). SI SBP obtained from ABPM data for

individuals who rose for sahur was lower than in those who did not (p=0.027). In other words,

BPV was higher in those individuals who performed the sahur (Table 2).

Discussion

Fasting involves avoiding food and/or drink for specific periods of time in order to obtain

spiritual benefits in various faith systems or else for health benefits. Fasting in humans

involves abstaining from food and/or drink for periods between 12 h and 3 weeks. Fasting

every alternate day or twice weekly is defined as intermittent fasting, while abstaining from

food and/or drink for several days every two or more weeks is defined as periodic fasting

[11]. The fasting undertaken over a specific number of hours for a specific number of days in

various faith systems is defined as intermittent fasting. In the Judaic faith, believers fast for 26

days over Yom Kippur. Some Orthodox Christians fast by abstaining from animal products

for 49 days during Easter, while Muslims fast for one month during Ramadan every year.

Hypertensive patients frequently seek medical advice to inquire whether there are any

objections in terms of health to intermittent fasting. Few studies have investigated the effect

of intermittent fasting on course of BP in hypertensive patients, and none have assessed its

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ACCEPTED MANUSCRIPT impact on BPV. We therefore think that there is a need for scientific studies showing how

these patient groups are affected by intermittent fasting.

The positive effects of long-term fasting were best shown by Muller et al. in patients with

rheumatoid arthritis, the authors reporting a decrease in inflammation and pain with long-term

fasting in this patient group [12]. Previous studies have also shown that intermittent fasting

may have potentially beneficial effects in the prevention and treatment of diseases such as

obesity, type 2 diabetes mellitus and cardiovascular diseases [1,2]. A few studies have

considered the effect on BP of intermittent fasting as a religious observance recommended at

different times and for different periods of time in various faiths. The few previous studies

involving hypertensive patients have shown a significant decrease in BP values during

intermittent fasting compared to pre- intermittent fasting levels [13-15]. However, a few

studies have also observed no change in BP during intermittent fasting [3,4]. In a study of

normotensive individuals, Samad et al. determined a significant decrease in SBP and DBP

levels during intermittent fasting compared to pre-fasting values [16]. In our study, we

observed a significant decrease in office BP, DBP and heart rate among fasting subjects. No

significant change was observed in home measurements and central BP values. Among the

ABPM data, while there was no change in SBP, we determined a significant decrease in DBP,

MAP and heart rate values. When we analyzed office, home, ABPM and central BP data

together, we observed a general decrease in BP values in individuals fasting intermittently.

We think that low BP values being observed in some studies while there was no change in

others may be due to variations among BP measurement techniques (office, home and

ABPM). This study differs from previous research in that it was performed among pre-

hypertensive and newly diagnosed hypertensive individuals and used four methods of

measurement.

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ACCEPTED MANUSCRIPT We also investigated how 24-h urinary sodium excretion was affected by intermittent fasting,

and observed that both urinary volume and sodium excretion were lower during the

intermittent fasting period compared to pre- intermittent fasting levels. Very few previous

studies have analyzed the effect of fasting on urinary sodium excretion. These studies have

also shown that fasting reduces urinary volume and sodium excretion [17]. High salt

consumption has long been known to be closely associated with high BP and HT-related

organ damage. A reduction in salt intake is therefore recommended as a lifestyle change in

hypertensive patients [18-21]. A significant decrease in patients’ salt excretion was

determined during intermittent fasting in this study. We similarly determined a significant

decrease in BP values at office and ABPM BP measurements. We think that decreased salt

consumption may have contributed to the fall in BP in the intermittent fasting period. Few

studies have investigated the relation between salt consumption and BPV. Özkayar et al.

reported a positive association between salt intake in diet and BPV in 136 primary

hypertensive patients [22]. However, we determined no relation between salt intake in diet

and BPV in our study. The relationship between salt consumption and BPV remains unclear.

The inconsistency between Özkayar et al.’s results and ours may derive from our study

involving more pre-hypertensive and newly diagnosed stage 1 hypertensive patients, and from

their not using antihypertensive medication.

Several studies have shown that the 24-h course of BP is affected by routine activities such as

sleep, wakefulness, physical activity, nutrition and emotional stimuli, while 24-h BPV is

affected by various humoral and vasomotor factors, particularly sympathetic activity [23,24].

Experimental and clinical studies have shown that a low-calories diet leads to a fall in BP, and

there are studies showing increases in BP during refeeding. These studies have shown an

increase in sympathetic tonus in the refeeding stage [25,26]. We hypothesized that repletion

following a prolonged period of fasting and an alteration in sleep periods (rising before sun-

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ACCEPTED MANUSCRIPT up) might lead to an increase in BPV. We observed an increase in BPV in the intermittent

fasting period at calculation of BPV from ABPM data. Our scan of the literature revealed no

previous studies investigating the relation between BPV and fasting. Analysis of the

parameters affecting BPV revealed that BMI and rising before sun-up both affected BPV.

BPV was higher among individuals rising for sahur. We attributed this to waking and

returning to sleep and the consumption of an extra meal between the two. Variability was low

during the intermittent fasting period among individuals with high BMI, but there was no

relation between BMI and BPV before the intermittent fasting period. Recent studies have

shown greater mean BP and BPV in overweight or obese patients [27,28]. BPV being low in

patients with high BMI during fasting in our study may be attributed to patients with high

BMI tolerating hunger better than thinner patients, and to lower hormonal variation.

The main objective for many years in the treatment of hypertension has been to lower BP [7].

However, in recent years, in addition to BP, high BPV has also been shown in numerous

studies to be important in the occurrence and progression of cardiac, renal and cerebral events

[29,30]. Studies have shown that an increase in BPV is associated with a decrease in

microalbuminuria and/or glomerular filtration rate, left ventricular hypertrophy and stroke

[29-31]. We determined an increase in BPV during intermittent fasting, particularly in

patients with patients with impaired sleep and wakefulness periods and rising to consume an

extra meal. We think that our findings should be further investigated with studies of BPV and

renal, cardiac and cerebrovascular outcomes.

The low patient number represents one limitation of our study of the effect of intermittent

fasting on BPV. However, we think that the absence of any previous studies evaluating the

effect of intermittent fasting on BPV and that our use of four methods for determining BP

nevertheless make our study particularly valuable. Another limitation of this study is that we

were unable to measure the amount and variety of foods consumed by our patients. However,

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ACCEPTED MANUSCRIPT we think that our measurement of 24-h urine and salt excretion make it possible to draw

conclusions concerning salt consumption at least.

In conclusion, there are increasing questions concerning whether intermittent fasting leads to

health problems in hypertensive and pre-hypertensive patients. In this study we investigated

the effects of intermittent fasting on central BP with office, home, ABPM and central BP

measurements. These four methods have not been used together in any previous study. The

effect of intermittent fasting on BPV has also not been investigated previously. Our results

show that intermittent fasting produces a significant decrease in office and ABPM BP values

but causes no significant change in central BP and home measurements. At the same time, we

determined that BPV increases during intermittent fasting, particularly in patients who rise to

eat before sun-up. We think that the long-term cardiovascular effects of intermittent fasting

should now be analyzed by wider, prospective studies.

We report no conflict of interest

This study was supported by the Turkish Society of Hypertension

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ACCEPTED MANUSCRIPT Figure legends

Figure 1a: Comparison of SBP SI values before and during intermittent fasting

p=0.012

Figure 1b: Comparison of DBP SI values before and during intermittent fasting

p=0.005

Figure 1c: Comparison of heart rate SI values before and during intermittent fasting

p=0.002

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ACCEPTED MANUSCRIPT Table 1: Patients demographic parameters and a comparison of the blood pressure measurements before and during intermittant fasting

n=60

Before intermittant fasting Median (Min.-Maks.)

During intermittant fasting Median(Min.-Maks.) p

Office SBP (mmHg) 122.75 (88.25-184.5) 116.88 (99-163.25) <0.001

DBP (mmHg) 77.38 (57.50-113.50) 77.38 (46.00-98.00) 0.039

Heart Rate (bpm) 80.63 (55.25-97.50) 75.63 (55.00-90.75) 0.003

Home (All Day) SBP (mmHg) 116.01 (91.47-151.74) 115.49 (89.51-155.76) NS

DBP (mmHg) 72.78 (57.54-101.34) 73.96 (56.74-99.16) NS

ABPM (All Day) (n=41) SBP(mmHg) 119.00 (100.00-176.00) 120.00 (95.00-151.00) NS

DBP(mmHg) 74.00 (56.00-110.00) 75.00 (60.00-94.00) NS

MAP(mmHg) 92.00 (78.00-140.00) 93.00 (80.00-120.00) NS

Day time SBP(mmHg) 120.00 (99.00-171.00) 120.00 (102.00-156.00) NS

DBP(mmHg) 75.00 (55.00-110.00) 78.00 (60.00-98.00) NS

MAP(mmHg) 94.00 (77.00-138.00) 97.00 (81.00-125.00) NS

Night Time SBP(mmHg) 117.00 (93.00-183.00) 111.50 (88.00-142.00) NS

DBP(mmHg) 73.00 (56.00-110.00) 69.00 (54.00-85.00) 0.003

MAP(mmHg) 92.00 (75.00-143.00) 88.00 (72.00-111.00) 0.025

Urine Sodium (mEq/day)

234.50 (129.00-465.00) 213.00 (50.00-390.00) 0.004

Volume (L) 2.3 (0.9-4.7) 2.0(0.5-2.5) 0.016

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Table 2: The affect of the eat before sunrise on Blood Pressure Variability

Don’t eat before sunrise Eat before sunrise p

Office BPV

CV SBP 0.03 (0-0.59) 0.04 (0.02-0.11) 0.047

CV DBP 0.04 (0.01-0.13) 0.04 (0.01-0.13) NS

CV Heart rate 0.04 (0.01-0.14) 0.03 (0.01-0.12) NS

SD SBP 3.32 (0-51,6) 5.62 (1.83-14.45) 0.029

SD DBP 2.87 (0.5-9.47) 3.32 (0.96-9.98) NS

SD Heart rate 2.63 (0.82-10.02) 2.38 (1-9.11) NS

Home BPV

CV SBP 0.07 (0.04-0.14) 0.08 (0.03-0.23) NS

CV DBP 0.08 (0.05-0.17) 0.09 (0.05-0.13) NS

CV Heart rate 0.08 (0.03-0.2) 0.08 (0.05-0.18) NS

SD SBP 8.1 (3.81-15.83) 8.88 (4.61-22.83) NS

SD DBP 5.85 (3.24-12.12) 6.57 (2.89-11.35) NS

SD Heart rate 6.33 (3.06-15.44) 6.57 (3.71-11.9) NS

ABPM BPV

SI SBP 0.32 (-0.87-5.73) -0.53 (-14.49-4.13) 0.027

SI DBP 0.37 (-3.34-8.65) -0.75 (-28.29-3.53) NS

SI Heart rate 0.97 (-3-4.31) 0.8 (-6.8-2.57) NS

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ACCEPTED MANUSCRIPT Intermittent fasting is a religious obligation performed by many believers worldwide

The effect on human health of intermittent fasting is uncertain

Hypertensive patients frequently seek medical advice to inquire whether there are any objections in terms of health to intermittent fasting.

No studies have investigated the effects of intermittent fasting on blood pressure variability

(BPV) and urinary sodium excretion in pre-hypertensive and/or newly diagnosed hypertensive

patients.

Our results show that intermittent fasting produces a significant decrease in office and ABPM BP values but causes no significant change in central BP and home measurements.