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Intermittent Fasting in Cardiovascular Disorders—An Overview

  • Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University , Toruń

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Intermittent fasting is a form of time restricted eating (typically 16 h fasting and 8 h eating), which has gained popularity in recent years and shows promise as a possible new paradigm in the approach to weight loss and the reduction of inflammation, and has many potential long term health benefits. In this review, the authors will incorporate many aspects of fasting, mainly focusing on its effects on the cardiovascular system, involving atherosclerosis progression, benefits for diabetes mellitus type 2, lowering of blood pressure, and exploring other cardiovascular risk factors (such as lipid profile and inflammation).
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Nutrients 2019, 11, 673; doi:10.3390/nu11030673
Intermittent Fasting in Cardiovascular Disorders—
An Overview
Bartosz Malinowski 1,*, Klaudia Zalewska 1, Anna Węsierska 1, Maya M. Sokołowska 1,
Maciej Socha 2, Grzegorz Liczner 1, Katarzyna Pawlak-Osińska 3 and Michał Wiciński 1
1 Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz,
Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland; (K.Z.); (A.W.); (M.S.S.); (G.L.); (M.W.)
2 Department of Obstetrics, Gynecology and Gynecological Oncology, Faculty of Medicine, Collegium
Medicum in Bydgoszcz, Nicolaus Copernicus University, Ujejskiego 75; 85-168 Bydgoszcz, Poland;
3 Department of Pathophysiology of Hearing and Balance System, Faculty of Medicine, Collegium Medicum
in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland;
* Correspondence:; Tel.: +48-509-294-517; Fax: +48-52-585-35-87
Received: 12 February 2019; Accepted: 18 March 2019; Published: 20 March 2019
Abstract: Intermittent fasting is a form of time restricted eating (typically 16 h fasting and 8 h eating),
which has gained popularity in recent years and shows promise as a possible new paradigm in the
approach to weight loss and the reduction of inflammation, and has many potential long term health
benefits. In this review, the authors will incorporate many aspects of fasting, mainly focusing on its
effects on the cardiovascular system, involving atherosclerosis progression, benefits for diabetes
mellitus type 2, lowering of blood pressure, and exploring other cardiovascular risk factors (such as
lipid profile and inflammation).
Keywords: intermittent fasting; cardiovascular diseases; lipid profile; atherosclerosis; blood
1. Introduction
Cardiovascular diseases are a serious problem in the modern world. According to WHO (World
Health Organization) data, 17.9 million people die every year due to cardiovascular diseases, which
is about one third of all deaths [1]. They most often affect people over 45 years of age. The mortality
rate is different in both sexes in any given period of life. Between the ages of 45–59, men predominate,
while after the age of 60, the death rate is higher in women [2]. These differences are related to the
cardio protective effect of estrogens in premenopausal women [3]. Modifiable and unmodifiable
factors contribute to the development of cardiovascular diseases. Age, gender, or genetic
determinants are factors beyond our control. However, smoking, obesity, lack of physical activity,
disorders of lipid metabolism, hypertension, diabetes, and poor diet are among the modifiable factors
[4]. The coexistence of two or more risk factors increases the likelihood of the disease occurrence.
Treatment of cardiovascular diseases includes patient training in the context of the importance of
lifestyle changes, taking into account pharmacotherapy and invasive therapy [5].
The control of risk factors allows for a reduction of mortality and pathogenicity, in particular in
patients with unrecognized cardiovascular disease [6]. Lifestyle adjustments, i.e., smoking cessation,
increasing physical activity, or ensuring proper body weight, reduces the risk of cardiovascular
disease. With the growing problem of obesity in the world, diet changes are an important modifiable
factor. Meals should be varied, similar to the Mediterranean diet. It is recommended to eat large
Nutrients 2019, 11, 673 2 of 18
amounts of vegetables, fruit, fish, and only whole-grain bread. The eating of red meat, sweetened
beverages, and excessively salty foods (daily salt intake < 5 g) should be avoided [5,7]. Large amounts
of alcohol should also be avoided. Consumption of spirits should be limited to 10 g/day in women
and 20 g/day in men [5].
Along with the growing epidemic of obesity, the search for new and effective dietetic solutions
aimed at reducing calories and reducing body mass was initiated. Currently, the intermittent fasting
(IF) diet is gaining popularity [8]. For many people, it is considered to be less restrictive compared to
traditional methods of calorie restriction (calorie restriction) [9]. It involves taking a normal, daily
caloric intake with the use of short, strict calorie restriction [10]. Meals are only consumed within a
strictly defined time within a day or week [8]. There are two basic varieties of the IF diet. The most
popular variation is time-restricted feeding. It may be used in three variants: 16/8, 18/6 and 20/4. 16:8,
consisting of a 16-h fast, and then an 8-h nutritional window. In a more rigorous approach, the
nutritional window can be shortened to 4 h [8]. Another protocol consists of a 24-h fasting period,
alternated with a 24-h eating period, repeated two or three times a week. There are two possible
systems, 5:2 or 4:3. In the 5:2 system, in which caloric restriction is used for two days a week, and a
regular diet for 5 days. The literature describes fasting periods as a consumption of about 400–600
kcal/day. Most people separate their fasting days [11]. In 2016, Carter et al. compared the effectiveness
of the IF diet in the 5:2 system with the continuous energy restriction (CER) diet. The authors found
that the IF diet may be an alternative for weight loss and glycemic control during 12 weeks. Moreover,
the IF diet presents a useful substitute to obese/overweight patients who find the CER diet difficult
to maintain [12].
The subtype of the IF diet is the ADF diet (alternate day fasting). It consists of alternating the
day when the energy limit is 75%, the so-called “fast day” and “feeding day”, during which food is
eaten ad libitum (at one’s pleasure, shortened to “ad lib”). The use of IF allows body weight to be
reduced and is cardio protective [9]. Cardioprotective effects of the ADF diet are probably associated
with a reduction of fat tissue (especially visceral fat tissue), increased adiponectin concentration, and
decreased leptin and low-density lipoprotein (LDL) concentration [13]. In other studies, individuals
following the ADF diet, after a period of dietary restriction, observed an increase in hunger during
the day, but also increase in satiety after a meal, which resulted in consumption difficulties [14].
Time-restricted feeding (TRF) is a type of IF diet that focuses on eating within a particular
window of time. Protocol may vary according to individual preferences and lifestyle. TRF involves
limiting intake to several hours (6–12 h). The TRF diet is of special interest among physically active
people due to reports on its effect on weight reduction while maintaining muscle mass. Thus, it may
help athletes to achieve the desired body mass for a specific sport category. Moro et al. provided a
trial on 34 resistance trained males who were randomly assigned to a time-restricted feeding or
normal diet group. The interventional group ate 100% of their energy needs during an 8 h eating
window each day with their caloric intake divided into three time-points (1 p.m.; 4 p.m.; 8 p.m.). The
normal diet group consumed 100% of their energy needs divided into three time-points (8 a.m.; 1
p.m.; 8 p.m.). After 8 weeks, analysis showed a decrease in fat mass in the TRF group compared to
the normal diet group, while the fat-free mass, and the muscle area of the arm and thigh remained
unchanged in both groups [15].
In contrast to traditional IF, TRF is usually performed on a daily basis and does not need
prescribed restrictions. Additionally, the fasting window may be planned during nighttime. Thus, it
can help some individuals to avoid night eating and follow a circadian rhythm.
Table 1 presents comparison of intermittent fasting protocols.
Nutrients 2019, 11, 673 3 of 18
Table 1. Comparison of intermittent fasting protocols [8,11].
Energy restriction for two
nonconsecutive days and ad libidum
intake for other five days.
Eating days—ad
libidum food
Fasting days—Low
or no-energy food
Ad libitum food intake
in specific timeframe
Night fasting period
according to circadian
5:2 Protocol ADF Protocol TRF Protocol Days of the
Fast Eat ~12-h Monday
Fast Fast ~12-h Tuesday
Eat Eat ~12-h Wednesday
Eat Fast ~12-h Thursday
Eat Eat ~12-h Friday
Fast Fast ~12-h Saturday
Fast Eat ~12-h Sunday
Abbreviations: ADF, alternate-day fasting; TRF, time-restricted feeding.
The above-mentioned diets can be successfully used in people who want to reduce their weight
to improve their health, but can also be implemented in a population of patients in whom obesity is
an important risk factor for the development of type II diabetes [10]. In addition, the IF diet can be
used as a supplement to training processes for people with a normal weight who want to improve
their health regardless of their weight loss. In these people, intensive energy restriction (IEF) requires
a concentration on energy restriction (ER) for specific days of the week, which is easier to achieve
than daily, continuous energy reduction, as is the case in traditional CER (continuous energy
restriction) [16]. Moreover, many beneficial metabolic effects, taking place during weight loss and
energy limitation, are associated only with the limitation of energy and are suppressed when a person
no longer has a negative energy balance [17].
However, according to the National Institute for Health and Care Excellence (NICE) guidelines
for the treatment of obesity in adults, routine use of very low calorie diets (VLCDs) in the therapeutic
regimen of obesity in adults is not recommended. According to this institute, such an approach
should be recommended when there is a clinical justification for rapid weight loss and it must supply
all necessary nutrients. Additionally, it should be attempted for a maximum of 12 weeks (continued
continuously or intermittently) [10].
Many studies based on human and animal models on weight loss using an IF diet confirm the
reduced risk of developing cardiovascular diseases. This is related to the modulating effect of the IF
diet on various risk factors of development, such as obesity, improper diet, insulin resistance, type II
diabetes, and arterial hypertension [11].
2. The Impact of Intermittent Fasting on Lipid Metabolism
Survival and preservation of species continuity depend, amongst others, on their access to food.
That is why living organisms have developed many adaptive mechanisms that allow them to survive
periods of famine. Some organisms in the periods where they lack access to food are dormant, for
example, yeasts entering the stationary phase [18]. In contrast, mammals have liver and adipose
tissue. These constitute an energy warehouse for them that allows them to survive during periods of
famine [19]. Fats are essential components of the human body. It is a diverse group in terms of the
structure and functions fulfilled in the body [20]. One of the most important functions is that of the
backup and energy function. Energy is contained within stored adipocytes, which under certain
conditions is released from them under the influence of enzymes—lipases [21]. After eating a meal,
the concentration of glucose in the body increases and then within a few hours, it returns to the state
it was before the meal. The concentration of ketones is low, because glycogen stores in the liver are
not depleted [19].
Nutrients 2019, 11, 673 4 of 18
During use of the IF diet, which consists of introducing fasting periods, there are marked
metabolic changes in the body [22]. For example, when using a diet during which all food during the
day is consumed in a 6-h nutritional window, the glucose level is elevated during and about 6 h after
a meal, but remains low for the remaining 16 h until the next day. During the 6–8 h in an 18-h fasting
window, ketones remain increased [19]. The human body is naturally adapted to such periods of
fasting and in the moment of starving, adaptation mechanisms are used to obtain energy. During
fasting, when glucose is exhausted, the body begins to utilize ketones that arise as a result of fatty
acid transformations [23,24]. Fatty acids and ketones become the main source of energy for cells. This
transition is called intermittent metabolic switching (IMS) or glucose-ketone (G-to-K) switchover.
Inverse switching, i.e., ketone-glucose (K-to-G), occurs after the interruption of fasting and meal
intake [22].
While the body is abstaining from food, the concentration of glucose, which is the basic energy
substrate, decreases. Glycolysis is inhibited. Glycogen reserves in the liver are consumed and the
process of gluconeogenesis is activated, during which fats are consumed. In addition, insulin and
IGF-1 (insulin-like growth factor-1) levels are reduced in blood and glucagon levels rise. Fatty acids
released from fat cells in the process of lipolysis of triacylglycerol and diacylglycerol are released
[23]. They are then transported to the liver cells, where they are converted into β-hydroxybutyrate
(BHB) and acetoacetate (AcAc) in the β-oxidation process and are further released into the blood and
used as a source of energy for body cells, including the brain [24]. Such biochemical changes are
accompanied by cellular and molecular adaptations of neuronal networks in the brain. The result is
an improvement of their functionality and resistance to stress, injuries, and diseases [23].
The above biochemical transformations of lipids, along with following the IF diet, result in
weight loss and changes in lipid parameters. According to studies conducted by Surabhi Bhutani et
al., during the use of alternative days on an empty stomach—ADF (alternate day fasting)—for 2–3
weeks showed a reduction in body weight by 3%, while longer attempts to use ADF showed a
reduction of 8% and reduced fat mass in viscera. In addition, the levels of total cholesterol (TC)
triglycerides and low density cholesterol (LDL) and the size of these molecules were reduced.
Changes in these parameters limit the risk of developing coronary heart disease (CHD) [25].
The effects of the IF diet on body weight and LDL cholesterol levels have also been proven in
studies conducted by Wilson et al., on 8-week-old mice (39 males and 49 females). These mice were
fed high-fat and sugar foods for 24 weeks, and after 12 weeks, they were divided into five groups.
The first group were overweight control mice—OBC; the second group were mice without
intervention—CON; the third group were mice subjected to the IF diet; the next group were mice
subjected to high intensity interval training (HIIT); and the last group were mice subjected to a
combination of IF and HIIT. Both IF, and IF and HIIT caused a decrease in body weight and low
density lipoproteins (LDL), compared to the HIT and CON groups. These results demonstrate the
effectiveness of weight loss despite the simultaneous intake of high-fat and sugar foods [26].
Studies on human individuals are summarized in Table 2.
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Table 2. Impact of intermittent fasting on lipid profile.
First Author and
Reference Number
of Enrolled
Description Time Lipids NCT
Harvie et al. 2011 [27] 107 Overweight or obese
premenopausal women 6 months NS (LDL, TGs,
HDL) NCT02679989
Varady et al. 2013 [28] 15 Overweight individuals
BMI 20–29.9 kg/m2 12 weeks
TC (
< 0.01)
LDL (p < 0.01)
TGs (p < 0.01)
Bhutani et al. 2013 [25] 83 Obese individuals
BMI 30–39.9 kg/m2 12 weeks
LDL (p < 0.05)
HDL (p < 0.05)
Eshghinia et al, 2013 [29] 15
Overweight or
obese women
BMI ≥ 25 kg/m2
8 weeks NS (LDL, TGs,
HDL) -
Teng et al. 2013 [30] 28 Malay Men
BMI 23–29.9 kg/m2 12 weeks
TC (
< 0.001)
LDL (p < 0.05)
Harvie et al, 2013 [31] 77 Overweight or
obese women 3 months NS (LDL, TGs,
HDL) NCT00869466
et al. 2016 [32] 23 Obese individuals
BMI 30–39.9 kg/m2 6 weeks
Abbreviations: NS, not statistically significant (p > 0.05); LDL, low-density lipoprotein; TGs,
triglycerides; HDL, high-density lipoprotein; TC, total cholesterol. Only studies from the past 10 years
with full data published were considered.
3. The Impact of Intermittent Fasting on Inflammatory Biomarkers
Atherosclerosis is the leading cause of vascular disease in the world. It is a serious problem of
pathogenicity and mortality in both developed and developing countries. It is manifested by clinical
symptoms, such as ischemic heart disease, peripheral artery disease, and ischemic stroke. It is
responsible for acute myocardial infarction and cerebrovascular events, and it is responsible for the
most deaths from cardiovascular causes in the world [33,34].
Atherosclerosis is a chronic inflammatory disease during which atherosclerotic plaque form in
arterial vessels, which causes sclerosis of the walls and narrowing of the arteries. The development
of atherosclerotic plaque is caused by vascular endothelial dysfunction and long-term exposure to
cardiovascular disease development factors. One of the most important risk factors is high levels of
low density lipoproteins (LDLs) [34]. Excess LDLs accumulated in the sub-epithelial layer of arterial
walls is oxidized to oxLDL [35]. This induces an inflammatory response and adhesion to the
endothelium of blood leukocytes, mainly monocytes. They migrate to the inner membrane of the
vessels and are converted into macrophages [36]. Macrophages, through internalization with oxLDL,
are transformed into foam cells that present antigens to immune cells. Activated cells release factors
that contribute to smooth muscle cell migration from the medial to the inner membrane [37]. Vascular
smooth muscle cells over proliferate and secrete extracellular matrix proteins. There is a further
accumulation of lipids both within cells and extracellularly [38]. The majority of risk factors for
cardiovascular diseases and factors of atherosclerosis may be modified [39]. One of the modifications
is the use of the IF diet.
Inflammation is an important element of development. Pro-inflammatory factors, such as
homocysteine, interleukin 6 (IL6), or C reactive protein (CRP), contribute to the development of
atherosclerotic plaque. In research conducted by Aksungar et al., the effect of the IF diet on reducing
the concentration of the above-mentioned pro-inflammatory factors was demonstrated. The
experiment was attended by 40 healthy participants with the correct body mass index (BMI) who
fasted during Ramadan and 28 participants, respectively, selected in terms of age and BMI index who
did not fast. Venous blood samples to examine the concentration of the above-mentioned pro-
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inflammatory factors were collected one week before the start of Ramadan, in the last week of fasting,
and three weeks after [40].
Adiponectin is a collagen-like plasma protein whose concentration decreases in the course of
atherosclerosis, insulin resistance, diabetes, and coronary disease [41]. The use of the IF diet increases
the secretion of adiponectin from adipocytes [42]. There is an inverse correlation between plasma
adiponectin levels and body weight. Cambuli et al. examined 104 children with obesity. They
compared the starting concentration of adiponectin with the concentration observed after one year
of a diet and increased physical activity. This concentration increased by 245%. The increase in the
adiponectin concentration was proportional to the reduction of body weight [43]. Adiponectin fulfills
its functions by acting on adiponectin receptors found in two isoforms—AdipoR1 and AdipoR [44].
It exhibits anti-atherosclerotic and anti-inflammatory effects by inhibiting the adhesion of monocytes
to endothelial cells. It also inhibits the excretion of the vascular cell adhesion molecule 1 (VCAM-1),
endothelial-leukocyte adhesion molecule 1 (ELAM-1), and intracellular adhesive molecule 1 (ICAM-
1) on vascular endothelial cells. This was proven by Ouchi et al. in in vitro studies on human aortic
endothelial cells incubated for 18 h in the presence of adiponectin. Adhesion, induced by tumor
necrosis factor alpha (TNF-alpha), of THP-1 line monocytes to human aortic endothelial cells was
assessed by an adhesion assay. Expression of the molecules was measured by ELISA (enzyme-linked
immunosorbent assay). [45,46]. Anti-atherosclerotic action of adiponectin has been proven in many
animal models and cell cultures [44]. For example, in studies conducted by Okamoto et al., using
reverse transcriptase polymerase chain reaction (real-time) and ELISA testing, it was demonstrated
that adiponectin has anti-inflammatory activity in human macrophages by inhibiting the production
of CXC 3 receptor chemokine ligands. In in vivo studies on mice deficient in apolipoprotein
E/adiponectin, there was an increase in IP-10 in plasma, and increased accumulation of T
lymphocytes in vessels and atherosclerosis compared to a single apoE deficiency [47]. Matsuda et al.
demonstrated in adiponectin-deficient mice that a deficiency of this protein causes intimal thickening
and increases the proliferation and migration of smooth muscle cells by increasing the expression of
HB-EGF (heparin-binding epidermal growth factor) [48]. The association of the IF diet with increased
concentrations of adiponectin was proven in studies conducted by Wan et al. These studies were
carried out on rats assigned to groups with an ad lib diet and with IF for 3 months. Animals with an
IF diet were deprived of food for 24 h, every other day. To induce myocardial infarction, the rats’ left
coronary artery was ligated. Animals with an IF diet had a higher adiponectin concentration and the
area of ischemia was smaller. Moreover, significantly lower inflammatory indexes were observed,
leukocytes and IL6, compared to rats with an ad lib diet [49].
An important hormone secreted by adipocytes is leptin [42]. It has a pro-atherogenic effect. Its
concentration is elevated in obese people, and is correlated with body mass index (BMI), total
cholesterol, triglycerides, blood pressure, and inflammation markers. These correlations were
confirmed in studies conducted by Sattar et al., in which leptin concentrations were determined in
550 men with fatal coronary heart disease (fatal CHD) or nonfatal myocardial infarction (nonfatal MI)
and in 1184 control patients included in a prospective study on 5561 British men [50]. The
concentration of leptin decreases body weight when using the IF diet. Leptin hyperactivity reduces
the risk of atherosclerosis by reducing platelet aggregation and decreasing endothelial cell
proliferation and migration [51].
Resistin plays an important role in the pathogenesis of atherosclerosis. This is a cytokine derived
from adipocytes [52]. Its concentration correlates with resistance to insulin and obesity. It has pro-
inflammatory activity [53]. It also promotes the pro-inflammatory activity of neutrophils and
macrophages as well as the formation of extracellular deposits in vessels. This happens through the
inhibition of AMP-activated protein kinase activation, responsible for the inhibition of neutrophil
activity [54]. Resistin increases the expression of chemotactic monocyte 1 protein (MCP-1) and
sICAM-1 in vascular endothelial cells. These observations were made by Burnett and his team in
studies in which they incubated mouse aortic endothelial cells with a recombinant resistin [52].
Research carried out by Bhutani et al. is proof that the ADF diet shows activity in modulating
adipokines. As a result, it has cardio-protective and anti-sclerotic effects. The study included 16 obese
Nutrients 2019, 11, 673 7 of 18
people—12 women and 4 men. It lasted for 10 weeks and included three phases of dietary
interventions. The first two weeks were the control phase, the next 4 weeks included the ADF diet,
in which the feeding time was monitored, and the last 4 week were ADF with a self-fed nutrition
time by the patient. After 8 weeks of using the ADF diet, there was a decrease in leptin concentrations,
which was associated with a decreased body weight and fat content. The concentration of resistin
significantly decreased after using the ADF diet, which probably was associated with a decrease in
body weight [42].
Studies on human individuals are summarized in Table 3.
Table 3. Impact of intermittent fasting on inflammatory markers’ concentration.
First Author and
Reference Number
Number of
Enrolled Participants Description Time Inflammatory Biomarkers NCT Number
Harvie et al. 2013 [31] 77 Overweight or
obese women 3 months NS (IL6, TNFα,
leptin, adiponectin) NCT00869466
Varady et al. 2013 [28] 15 Overweight individuals
BMI 20–29.9 kg/m2 12 weeks
CRP (p = 0.01)
Leptin (p = 0.03)
Adiponectin (p < 0.01)
Bhutani et al. 2013 [25] 83 Obese individuals
BMI 30–39.9 kg/m2 12 weeks NS CRP NCT00960505
Hoddy et al. 2016 [55] 59 Obese individuals
BMI 30–39.9 kg/m2 10 weeks Leptin (p < 0.05) -
Chowdhury et al. 2016
[32] 23 Obese individuals
BMI 30–39.9 kg/m2 6 weeks NS (IL6, CRP,
leptin, adiponectin) -
Safavi et al. 2017 [56] 34 Male individuals 16–64
years old (Ramadan) 4 weeks NS (adiponectin, TNFα) -
Abbreviations: NS, not statistically significant (p > 0.05); IL6, interleukin 6; CRP, C-reactive protein;
TNFα, tumor necrosis factor α; Only studies from the past 10 years with full data published were
4. The Impact of Intermittent Fasting on Blood Pressure
Hypertension is a common disorder of the modern world. In the United States, this problem
affects 86 million adults. It is a risk factor for cardiovascular disease, stroke, and chronic kidney
disease [57]. It is defined as the occurrence of systolic blood pressure (SBP) in the amount of 140
mmHg and more, or diastolic blood pressure (DBP) of 90 mmHg or more [58].
The use of an IF diet has a beneficial effect on lowering blood pressure. This has been
documented in animal studies, and later, the effectiveness of the diet was confirmed in humans.
Studies conducted at the University at Buffalo in the United States in male Sprague-Dawley rats
confirmed the beneficial effect of the diet on the cardiovascular system. The animals were subjected
to a reduced calorie diet or the IF diet was maintained, in which they were fed every other day under
a circadian rhythm. To control the heart function, telemetry transmitters were implanted. After a few
weeks of observation, a decrease in SBP and DBP blood pressure was noted, as well as a reduction in
heart rate [59]. The effectiveness of the diet has also been confirmed in humans in studies conducted
at the Buchinger Wilhelmi clinic in Germany. The study group consisted of 1422 people who were
subjected to one-year follow-up during the IF diet [22]. The period of fasting was from 4–21 days.
Daily meals of 200–250 kcal were accepted. The observed effect of the IF diet on the cardiovascular
system was the same as in animals. The study proved the reduction of SBP and DBP in groups of
people who fasted for a long period of time. The mechanism of the pressure drop may be associated
with an increase in parasympathetic activity due to the brain-derived neurotrophic factor (BDNF),
increased norepinephrine excretion through the kidneys, and increased sensitivity of natriuretic
peptides and insulin [22]. It was observed that cardiovascular health benefits do not last longer than
the period of the IF diet. After its completion, the pressure values return to their initial values [59].
The mechanism of low blood pressure associated with the activation of the parasympathetic
system is based on the increased activity of the cholinergic neurons of the cerebrospinal stem [19,60].
Brain-derived neurotrophic factor (BDNF) is mainly produced in response to the activation of
glutamatergic receptors, but the IF diet is also somewhat stimulating. The influence of the factor on
heart rate and blood pressure has been proven in studies conducted in mice at the George
Nutrients 2019, 11, 673 8 of 18
Washington University. Male heterozygous and congenic wild-type mouse mice were tested. In both
groups, transmitters were implanted to monitor heart rate. Wild-type mice were infused with
recombinant human BDNF into the cerebral ventricles, while mice were infused with the mutated
solution of PBS. After 4 weeks of observation, it was noted that the heart rate in mice with
intraventricular infusion of the factor was significantly lower compared to mice with PBS infusion.
In addition, the changes were independent to the time of day. To explain the mechanism of the
reduction of the heart rate in the presence of BDNF, further tests in mice were performed. Both groups
were given anti-sympathetic drugs, atenolol, and anti-parasympathetic drugs, atropine. All mice
responded to atenolol with a reduction in heart rate. However, with atropine, the heart rate
significantly increased in wild-type mice compared to the mutant mice. This study proved the effect
of the BDNF factor on the increase in the activity of the parasympathetic system [60]. BDNF increases
the synthesis and release of acetylcholine by cholinergic neurons [61]. The cardiac function is
controlled by the release of acetylcholine through the vagus nerve to the sinoatrial node, where it
reduces the heart rate. In addition, the neurotransmitter expands the blood vessels, causing a
reduction blood pressure [62].
Studies on human individuals are summarized in Table 4.
Table 4. Impact of intermittent fasting on blood pressure.
First Author and
of Enrolled Participants Description Time Blood Pressure BDNF NCT Number
Harvie et al.
2011 [27] 107 Overweight or obese
premenopausal women 6 months Systolic (
= 0.99)
Diastolic (p = 0.84) NS NCT02679989
Varady et al.
2013 [28] 15 (5 M/10 F) Overweight individuals
BMI 20–29.9 kg/m2 12 weeks (p = 0.51) - NCT00960505
Bhutani et al.
2013 [25] 83 (3 M/80 F) Obese individuals
BMI 30–39.9 kg/m2 12 weeks Systolic (p = 0.254)
Diastolic (p = 0.570) - NCT00960505
Eshghinia et al.
2013 [29] 15 F
Overweight or
obese women
BMI ≥25 kg/m2
8 weeks Systolic (p < 0.001)
Diastolic (p < 0.05) - -
Teng et al.
2013 [30] 28 M Malay Men BMI
23–29.9 kg/m2 12 weeks Systolic (p < 0.05)
Diastolic (p < 0.05) - NCT01665482
Erdem et al.
2018 [63] 60
Individuals from the
Cappadocia cohort with
prehypertension and
hypertension SBP
12—139 and ≥140;
DBP 80–89 and ≥90 mmHg
Systolic (p < 0.001)
Diastolic (p < 0.039) -
Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; BDNF, brain-derived
neurotrophic factor; M, male; F, female. Only studies from the past 10 years with full data published
were considered.
5. The Impact of IF Diets on Other Important Factors in the Development of Cardiovascular
Other modifiable factors of cardiovascular diseases affecting the intermittent fasting diet are,
among others, obesity and diabetes. Obesity and being overweight is one of the most predisposing
factors for the development of cardiovascular disease, as well as other metabolic syndromes,
including diabetes [64,65]. Most evidence supporting the connection between obesity, overweight,
and cardiovascular disease (CVD) incidences are based one-time-point measurements. It must be
mentioned that prediction will be different for individuals who have just become overweight
compared to those who have been obese for years. It was proven in the Framingham Cohort Study
that all cause death risk increased simultaneously with an increased duration of obesity (every 2 years
lived with obesity, risk of CVD mortality raised 7%). In the studies conducted on humans and on
animal models, the beneficial effect of the IF diet on body weight and glycemic parameters was
proven. In 2017 Trepanowski et al. provided a single-center randomized clinical trial of obese
individuals (mean BMI = 34) to compare the effects of ADF to daily calorie restriction on weight
reduction, weight maintenance, and CVD risk predictors [66]. Scientists divided 100 participants into
three groups for 1 year (1st group = ADF, 25% energy needs on fast days, 125% of energy needs on
Nutrients 2019, 11, 673 9 of 18
feast days; 2nd group = calorie restriction, 75% of energy needs every day; 3rd group = no intervention
group). The trial included two phases: 6-month weight loss and 6-month weight maintenance. The
authors found that the mean weight loss was similar for the ADF-group and those in the CR-group
(calorie restriction; 75% of energy needs every day) at 6 and 12 months. Additionally, it was observed
that participants in the ADF group ate more than was prescribed on fast days, and less than
prescribed on feast days, while the CR-group followed their prescribed goals without disturbances.
It clearly shows that the ADF diet is harder to comply with when compared to the CR system,
especially in long term use. Moreover, there were no significant differences between the ADF and CR
groups in terms of heart rate, blood pressure, fasting glucose, fasting insulin, triglycerides, and CRP
at both time-point assessments [66]. However, the study did not match food intake and meal
frequency also did not control for whether participants followed a diet regimen.
In 2018, Schubel et al. conducted a randomized controlled trial to test if the 5:2 diet (ICR—
intermittent calorie restriction) is more beneficial in the context of adipose tissue gene expression,
anthropometric, body composition, and circulating biomarkers measurements than continuous
calorie restriction (CCR) [67]. Investigators randomly assigned 150 overweight and obese
nonsmokers to the ICR/5:2 group (5 days without energy restriction and 2 days with 75% energy
deficit) and the CCR group (daily energy deficit 20%), or a non-intervention group (control group—
without energy restriction). The trial was divided into a 12 weeks intervention phase, 12 weeks
maintenance phase, and 26 weeks follow-up phase. Weight change over the intervention phase was
−7.1% ± 0.7% (mean ± SEM) with ICR, −5.2% ± 0.6% with CCR, and −3.3% ± 0.6% with the control
regimen (poverall < 0.001, pICR vs. CCR = 0.053). At the final time-point of week 50, weight loss was −5.2% ±
1.2% with ICR, −4.9% ± 1.1% with CCR, and −1.7% ± 0.8% with the control regimen (poverall = 0.01,
pICR vs. CCR = 0.89). The authors did not observe any significant differences between the 5:2 diet and the
continuous calorie restriction diet in the context of circulating biomarkers and adipose tissue genes
Sutton et al. tried to answer the question of whether health benefits depend on weight loss or
other non-weight loss mechanisms in humans. Scientists prepared a proof-concept-study based on
early time-restricted feeding (eTRF), a form of intermittent fasting that includes eating early in the
day according to the circadian rhythm. Individuals with prediabetes were randomly assigned to
eTRF (6 h feeding time, dinner before 3 p.m.) or a control group (12 h feeding time). After 5 weeks of
observations, it was proven that eTRF improved beta-cell responsiveness, insulin sensitivity, blood
pressure, oxidative stress, and appetite [68].
At the State University of New Jersey, studies were carried out on male C57/BL6 mice in which
the effects of the IF diet on the body were studied. Initially, all animals were fed a high-fat diet (45%
fat) over a period of 8 weeks to obtain an obese phenotype. The mice were then divided into four
groups: The control group included mice on the high-fat ad lib diet (group 1); exercise groups: High-
fat diet for two days, then five-day fasting (group 2); low-fat diet (10% fat/group 3); and a group with
IF (group 4). After 4 weeks of diet use, a decrease in body weight and body fat content was observed
in all experimental groups compared to the control group. Glucose concentration after oral glucose
load as well as insulin tolerance were also investigated. The results in all study groups showed lower
blood glucose, glycated hemoglobin levels, and increased insulin sensitivity compared to the control
group [69]. The effects of the IF diet on weight loss were also confirmed in studies in the human
population in Manchester. Women who were overweight or obese in the pre-menopausal age were
subjected to an attempt to reduce calories by 25% based on the Mediterranean diet for 6 months. After
the end of the study, a decrease in weight was observed in women along with a reduction of
abdominal circumference and a decrease in adipose tissue content. Reductions in weight also had a
positive effect on well-being. In addition to body weight, women were also tested for insulin
sensitivity and glucose. The results also proved the beneficial effect of the IF diet on glycemic
parameters. Insulin resistance in the study group was assessed using the HOMA index [27].
To determine the effect of the IF diet on glucose metabolism, the study also investigated people
with diabetes. The particularly positive effects of IF diets were observed in patients with type 2
diabetes. Type 2 diabetes is a common metabolic disorder in the world. It correlates with an increase
Nutrients 2019, 11, 673 10 of 18
in obesity rates and sedentary lifestyles. Limiting the development of diabetes prevents many
diseases, including cardiovascular diseases, neuropathy, retinopathy, and kidney disease [70].
Diabetes induced by obesity is characterized by hyperglycemia, insulin resistance, and progressive
beta cell failure. The use of the IF diet effectively improves glucose metabolism in patients with type
2 diabetes. This was demonstrated in the Diabetes Remission Clinical Trial (DiRECT) in which
diabetes mellitus after a hypocaloric diet was observed. Participants under constant medical care
consumed meals of about 850 calories/day for 12 weeks [71]. It was proven that weight loss
normalizes fasting blood glucose, significantly reduces glycated hemoglobin (HBa1c), and increases
insulin sensitivity in people with type 2 diabetes [71,72]. The mechanism of this phenomenon is
associated with increased sensitivity of the insulin receptor after the IF diet, due to which insulin
stimulates quick uptake of glucose by muscle cells and hepatocytes [73]. However, the return to daily
nutritional conditions resulted in fasting glucose concentrations returning to the baseline values [70].
There is also evidence of an effect of the IF diet on the activity of pancreatic B-cells in patients
with type 1 diabetes. This is confirmed by the study on rats with streptozotocin-induced diabetes. At
the same time, the control group was tested and the citrate buffer was injected. For 30 days, the
animals were exposed to starvation during the night or had a limited food supply. After observation,
a decrease in glucose concentration, an increase in insulin in plasma, a decreased HOMA index, and
an increase in the number of pancreatic B-cell cells in streptozotocin-induced rats on the IF diet [74]
were observed. Decreased apoptosis of B cells under the influence of diet was also observed in mice
with type 2 diabetes [75]. There is not much known about the mechanisms by which diet improves
glucose metabolism. There is a hypothesis that the use of the IF diet does not increase insulin
sensitivity, but increases the mass of pancreatic islet B cells, which in turn causes an increase in insulin
in the plasma, reducing blood glucose. Another hypothesis is the impact of autophagy on beneficial
effects of the IF diet in diabetic patients. In the conditions of the IF diet, an increased activity of
autophagy in the pancreatic islets is observed, which leads to an improvement in glucose tolerance
as a result of increased insulin secretion. The study also observed an increase in the expression of the
Ngn3 pancreatic regeneration marker, which plays a key role in the maturation of pancreatic B-cells
[76]. Although the mechanisms of the influence of the IF diet on diabetes remedies are not fully
understood, its beneficial effects can be applied as a potential therapy for treatment.
In addition to obesity and diabetes, a risk factor for cardiovascular disease is also
cerebrovascular diseases, including stroke. Stroke is the necrosis or damage to brain areas as a result
of interrupted blood supply. There are two subtypes of stroke: Ischemic stroke and hemorrhagic
stroke. This condition causes a wide range of disability depending on the extent of the stroke [77].
The IF diet has also had a beneficial effect on the prevention of stroke. This was confirmed in studies
at the National University of Singapore conducted on young mice (3 months) and middle aged mice
(9 months). The animals were subjected to an experimental focal ischemic stroke and then subjected
to an IF diet. After observation, it was concluded that the use of the IF diet reduces the risk of stroke
and its extent. The mechanism of this phenomenon is related to the protective action of the brain
tissue against oxidative stress, and it was proven that the diet regulates many neuroprotective
proteins present in the mouse brain after stroke. These proteins include BDNF, the basic fibroblast
growth factor (bFGF), stress response protein (Hsp70), and glucose-regulated protein 78 (GRP78). It
is believed that the protective effect of the IF diet on stroke is associated with the activation of
adenosine monophosphate-activated protein (AMPK) and SIRT1 protein in response to reduced
energy during fasting. AMPK and SIRT1 regulate neuroprotective proteins, preventing pathological
processes in brain cells [78].
Cardiovascular disease development is also predisposed with cardiac hypertrophy. Wang et al.
determined the effect of a long-term high-fat diet (HFD) and an IF diet on the hearts of mice. After 11
months, the cross-section of cardiomyocytes in HFD-fed mice was increased, whereas the IF diet did
not induce cardiac myopathy in mice. The intense fasting increased the active caspase 3, suggesting
that intermittent hunger may increase apoptosis and reduce autophagy in the heart. The mechanism
of the influence of the IF diet on normal heart mass, however, has not been thoroughly studied [79].
Studies on human individuals are summarized in Table 5.
Nutrients 2019, 11, 673 11 of 18
Table 5. The impact of intermittent fasting on obesity and glycemic profile.
First Author and
Reference Number
of Enrolled
Description Time Weight
Changes Glycemic Profile NCT
Harvie et al.
2011 [27] 107 Overweight or obese
premenopausal women 6 months NS insulin
NS glucose
Harvie et al.
2013 [31] 77 Overweight or
obese women 3 months NS insulin
NS (HbA1C, glucose)
Varady et al.
2013 [28] 15 Overweight individuals
BMI 20–29.9 kg/m2 12 weeks (p < 0.001) - NCT00960
Bhutani et al.
2013 [25] 83 Obese individuals
BMI 30–39.9 kg/m2 12 weeks (p < 0.05) NS (insulin, glucose) NCT00960
Hoddy et al.
2016 [55] 59 Obese individuals BMI
30–39.9 kg/m2 10 weeks (p < 0.0001) (insulin, glucose) -
Chowdhury et al.
2016 [32] 23 Obese individuals BMI
30–39.9 kg/m2 6 weeks (NS) NS (insulin, glucose) -
Safavi et al.
2017 [56] 34 Male individuals 16–64
years old (Ramadan) 4 weeks NS - -
Trepanowski et al.
2017 [66] 100 Obese individuals
BMI 34 12 months (comparing to
control group)
(insulin, glucose)
comparing to
control group
Schubel et al.
2018 [67] 150 Obese and overweight
BMI ≥ 25 50 weeks (comparing to
control group)
NS (insulin, glucose)
comparing to
control group
Abbreviations: NS-non significant. Only studies from the past 10 years with full data published were
6. Importance of Food Quality in the “Eating Window”
Diet plays an important role in the prophylaxis of cardiovascular diseases. Special attention
should be paid to nutraceuticals, which contain many beneficial substances for the human organism.
These substances, to name a few, are polyphenols, resveratrol, carotenoid, polyunsaturated fatty
acids (PUFAs), curcumin, and zinc [80]. Carotenoids are one of the basic ingredients in the
Mediterranean diet. They are present in vegetables, (especially in carrots), fruits, and also in seaweed.
Their beneficial effect in preventing cardiovascular events is not yet fully known. However, they are
attributed to antioxidant and anti-inflammatory functions due to the influence on lipoxygenases [81].
A nutraceutical deserving specific consideration is resveratrol. Its biologically active isomer is trans
3,5,4′-trihydroxystilbene. Grapes are rich in resveratrol, which is why the largest concentration is
found in red wine, but it is also found in blueberries, peanuts, and pistachios [80]. It has antioxidant
properties and it is helpful in the treatment of many disorders due to its cardioprotective effect. It
was observed that resveratrol may improve blood pressure. Wiciński et al. showed that a dose of 10
mg/kg of resveratrol per day increases the concentration of BDNF and reduces vascular smooth
muscle cells contractility [82]. Moreover, the same author proved that resveratrol (10 mg/kg per day)
may increase adiponectin concentrations, but the exact mechanism has not fully been elucidated [83].
Resveratrol inhibits hypercholesterolemia development. This was confirmed in tests conducted
on mice by Chen et al., who observed a decrease in lipid parameters within 8 weeks of a high fat diet
and administration of resveratrol in the dose of 200 mg/kg per day. Increased lipid metabolism after
administration of resveratrol is associated with elevated 7-α-hydroxylase activity in mice. The
enzyme is regulated by the liver receptor, LXR. It is involved in the cholesterol to 7-
hydroxycholesterol transformation and then to cholic acid, which results in increased production of
bile acids and lowers cholesterol in hepatocytes [84]. Nonetheless, in the analysis done by Sahebkar
on human models, no beneficial effects of resveratrol on dyslipidemia were observed. This can be
correlated with the metabolism of resveratrol as well as the first passing through the liver, which
results in its decrease in activity in the blood [85].
Polyphenols also contribute to the reduction of the lipid profile. Their highest concentration can
be found in mulberry leaves. The role of polyphenols in the reduction of lipid concentration is
attributed to the inhibition of the activity of the enzymes responsible for their synthesis. These include
fatty acid synthetase, 3-hydroxy-3-methylglutarylCoA reductase, or acetyl-CoA carboxylase.
Therefore, polyphenol extract from mulberry leaves decreases the culmination of fatty acids in the
liver through the activation of the AMP protein kinase pathway [86]. Other polyphenols, which also
Nutrients 2019, 11, 673 12 of 18
diminish the lipid profile, are found in black tea theaflavin. This has been documented in research
overseen by Jin et al. on rat models with a high-fat diet. The rats were fed black tea extract containing
highly purified mixtures of theaflavins at the same time. After the completion of the research, it was
observed that the total cholesterol concentration, LDL-C, and triglycerides were slightly decreased.
Theaflavin reduced the atherogenicity index, in addition to also ceasing alanine transaminase and
hepatic lipase activity [87]. Advantageous outcomes of polyphenol were also proven in the research
of Gunathilake, Wang, and Vasantha Rupasinghea. The study subjected rats with hypertension,
which were fed with the AIN-93G diet as the control group, the second group was fed a high fat diet,
while the third group was fed different doses of polyphenol rich fruit juices. The researchers
documented that the polyphenol rich juice supplement successfully lowered the total cholesterol
values and LDL-C in serum in addition to the cholesterol concentration in the liver. Apart from the
hypolipidemic function, blood pressure reduction was also recognized [88].
Protective actions in cardiovascular diseases also have unsaturated fatty acids, mainly omega-3
fatty acids: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A rich source of these
ingredients is fish oil [89]. Supplementation of unsaturated fatty acids reduces the concentration of
triacylglycerol from 25% to 30%, but can increase the concentration of LDL cholesterol in serum [90].
Schmidt et al. observed a decrease in triglyceride levels in dyslipidemia patients receiving
polyunsaturated n-3 fatty acids (PUFA). This was connected with the overexpression of peroxisome
proliferator-activated receptor (PPAR). Additionally, this diet reduces the triacylglycerol levels as the
result of decreased gene expression responsible for triacylglycerols’ synthesis (MOGAT3, MOGAT2,
and DGAT1). Such a diet also increases lipase lipoprotein (LP) activity and the VLDL catabolism.
This influences the inhibition of the expression of apoCIII and apoB, and through this, lowers VLDL
production [91].
It is also worth including curcumin and zinc in the diet as they have proven anti-atherosclerotic
action. According to the studies by Zhao et al., conducted on mice with apolipoprotein E deficiency,
treatment with curcumin inhibits macrophage transformation in foam cells. Moreover, they also
observed that curcumin therapy decreases oxLDL accumulation in macrophages. Curcumin
suppresses scavenger receptor class A (SR-A) expression and induces ATP-binding cassette A1
(ABCA1) synthesis. This is followed by prevention of oxLDL binding to SR-A and increased outflow
of ABCA1-dependent cholesterol [92].
Rahimi-Ardabili et al. showed that in hemodialyzed patients, administration of zinc may induce
a higher activity of paraoxonase enzymes [93]. These enzymes are located on cholesterol HDL
molecules, which prevent LDL oxidation [94].
7. Advantages and Disadvantages of Using the IF Diet
There are many studies conducted on humans and animals confirming the therapeutic
effectiveness of the IF diet [11]. It reduces body fat and body mass, which supports the healthy
functioning of the cardiovascular system, and reduces the incidence of myocardial infarction [95].
Individuals can influence the concentration of many metabolic biomarkers, for example, the
concentration of insulin and glucose, thereby reducing the risk of metabolic syndrome [13]. It also
reduces the risk of type 2 diabetes [9]. There are studies confirming the impact of long-term use of
the IF diet on the extension of the viability of individuals [14]. The IF diet positively affects the
functioning of the nervous system. By affecting the reduction of free radical formation in the body
and stress response systems, it protects neurons from environmental and genetic factors that cause
them to age [95].
Intermittent fasting also has its drawbacks. Periods of fasting of a few hours at the start cause
huge problems. This is accompanied by a bad mood at the beginning of the diet, such as fatigue or
dizziness, because the body needs time to get used to using ketones instead of glucose. Certainly, this
is not a good diet for patients with reactive hypoglycemia. Moreover, caloric restriction with the
simultaneous use of antidiabetic drugs may lead to severe hypoglycemia and even death [96]. In the
elderly, it is associated with an increased risk of cardiovascular disease, arrhythmia, and stroke.
Fluctuations in glucose concentration cause instability of the body, which results in an increased
Nutrients 2019, 11, 673 13 of 18
number of falls and frequent fractures due to osteoporosis [97]. The ACCORD trial confirmed greater
risk of cardiovascular events during the presence of hypoglycemia in both older and younger
individuals [98]. Higher risk of diabetic ketoacidosis is also not without significance, especially when
there is not enough insulin due to low food intake during fasting.
In addition, excessive restriction of calories causes dysregulation of hormone management. Such
disturbances may cause menstrual cycle disorders in women and reduced testosterone in men.
Intermittent fasting should not be used by children, pregnant women, and people performing heavy
physical work [99].
8. Summary
The IF diet limits many risk factors for the development of cardiovascular diseases and therefore
the occurrence of these diseases. Fatty acids and ketones become the main energy fuel, because the
body undergoes metabolic switching of glucose-ketone (G-to-K). By affecting the biochemical
transformations of lipids, it decreases body mass and has a positive influence on lipid profile
parameters—it reduces the concentration of total cholesterol, triglycerides, and LDL cholesterol.
Benefit from the use of the IF diet were confirmed in research on the development of
atherosclerosis. Intermittent fasting inhibits the development of atherosclerotic plaque by reducing
the concentration of inflammatory markers, such as IL-6, homocysteine, and CRP. The IF diet results
in an increase in plasma concentrations of adiponectin and a decrease in leptin and resistin
concentrations. By altering the levels of these adipokines, it inhibits the adhesion of monocytes to
vascular endothelial cells, neutrophils, and macrophage pro-active activity, and platelet aggregation.
The transformation of macrophages into foam cells, the formation of extracellular deposits in vessels,
and the proliferation and migration of endothelial cells into the inner arterial vascular membrane are
The beneficial effect of the diet was observed in the prevention of hypertension. The intermittent
fasting diet causes an increase of BDNF factor, which results in lowering the systolic and diastolic
blood pressure by activating the parasympathetic system. BDNF causes acetylcholine to be released
by the vagus nerve, which reduces the frequency of heart contractions.
The positive effect of the IF diet has also been documented in obese and diabetic people. The
reduced amount of food consumed when using the IF diet results in a decrease in body weight. It
also improves glucose metabolism and increases the sensitivity of tissues to insulin by increasing the
B cells of the pancreatic islets. The IF diet also limits cardiac hypertrophy.
It remains questionable if these benefits are solely due to weight loss or non-weight loss
mechanisms. The success of every type of diet depends on rule compliance—following a prescribed
diet according to the circadian rhythm.
Despite the intermittent fasting diet having many benefits, its disadvantages are not without
significance. Fasting may be dangerous and it is not recommended for people with hormonal
imbalances, pregnant and breastfeeding women, and diabetics. Moreover, people with eating
disorders, a BMI under 18.5, and underweight people are also not recommended to use the
intermittent fasting diet.
In recent years, the IF diet and its varieties have become increasingly popular. This diet not only
serves to reduce body weight, but can also be used as an effective non-pharmacological treatment
method. This has been proven through various studies performed on people and animals. However,
individuals’ current health and situation should be considered before commencing the IF diet.
Author Contributions: B.M., K.Z. and A.W. contributed to data analysis, interpretation of findings, and drafting
the article. M.M.S., M.S. and G.L. participated in data collection, K.P.-O. and M.W., participated in data
collection, critical revision and final approval.
Funding: The present work was supported by the Department of Pharmacology and Therapeutics, Faculty of
Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
Conflicts of Interest: The authors declare no conflict of interest.
Nutrients 2019, 11, 673 14 of 18
1. World Health Organization. Available online: (accessed
on 1 February 2019).
2. Cierniak-Piotrowska, M.; Marciniak, G.; Stańczak, J. GUS, Statystyka zgonów i umieralności z powodu
chorób układu krążenia 2016. Available online:
publicznej/rzadowa-rada ludnosciowa/publikacje-rzadowej-rady-ludnosciowej/ (accessed on 1 February
3. Grodstein, F.; Manson, J.; Stampfer, M. Hormone therapy and coronary heart disease: The role oftime since
menopause and age at hormone initiation. J. Womens Health 2006, 15, 35–44.
4. Matyjaszczyk, P.; Hoffmann, K.; Bryl, W. Epidemiology of selected risk factors for cardiovascular disease.
Prz Kardiodiabet 2011, 6, 255–262.
5. Jankowski, P. Principles of cardiovascular disease prophylaxis in 2018. Kardiol Inwazyjna 2017, 12, 42–48.
6. Yusuf, S.; Hawken, S.; Ounpuu, S.; Dans, T.; Avezum, A.; Lanas, F.; McQueen, M.; Budaj, A.; Pais, P.;
Varigos, J.; et al. INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated
with myocardial infarction in 52 countries: Case-control study. Lancet 2004, 364, 937–952.
7. Sofi, F.; Abbate, R.; Gensini, G.F.; Casini, A. Accruing evidenceon benefits of adherence to the
Mediterranean diet onhealth: An updated systematic review and meta-analysis. Am. J. Clin. Nutr. 2010, 92,
8. Johnstone, A. Fasting for weight loss. An effective strategy or latest dieting trend? Int. J. Obes. 2014, 39, 727–
9. Barnosky, A.R.; Hoddy, K.K.; Unterman, T.G.; Varady, K.A. Intermittent fasting vs. daily calorie restriction
for type 2 diabetes prevention: A review of human findings. Transl. Res. 2014, 164, 302–311.
10. Jane, L.; Atkinson, G.; Jaime, V.; Hamilton, S.; Waller, G.; Harrison, S. Intermittent fasting interventions for
the treatment of overweight and obesity in adults aged 18 years and over. A systematic review protocol.JBI
Database Syst. Rev. Implement. Rep. 2015, 13, 60–68.
11. Harvie, M.; Howell, A. Potential benefits and harms of intermittent energy restriction and intermittent
fasting amongst obese, overweight, and normal weight subjects—A narrative review of human and animal
evidence. Behav. Sci. 2017, 7, E4.
12. Carter S.; Clifton, P.M.; Keogh, J.B. The effects of intermittent compared to continuous energy restriction
on glycaemic control in type 2 diabetes; a pragmatic pilot trial. Diabetes Res. Clin. Pract. 2016, 122, 106–112.
13. Patterson, R.E.; Sears, D.D. Metabolic Effects of Intermittent Fasting. Annu. Rev. Nutr. 2017, 37, 371–393.
14. Heilbronn, L.K.; Smith, S.R.; Martin, C.K.; Anton, S.D.; Ravussin, E. Alternate-day fasting in nonobese
subjects: Effects on body weight, body composition, and energy metabolism. Am. J. Clin. Nutr. 2005, 81, 69–
15. Tatiana Moro, T.; Tinsley, G.; Bianco, A.; Marcolin, G.; Pacelli, Q.F.; Battaglia, G.; Palma, A.; Gentil, P.; Neri,
M.; Paoli, A. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength,
body composition, inflammation, and cardiovascular risk factors in resistance-trained males J. Transl. Med.
2016, 14, 290.
16. Anastasiou, C.A.; Karfopoulou, E.; Yannakoulia, M. Weight regaining: From statistics and behaviors to
physiology and metabolism. Metabolism 2015, 64, 1395–1407.
17. Wing, R.R.; Blair, E.H.; Bononi, P.; Marcus, M.D.; Watanabe, R.; Bergman, R.N. Caloric restriction per se is
a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese
NIDDM patients. Diabetes Care 1994, 17, 30–36.
18. Calixto, A. Life without food and the implications for neurodegeneration. Adv. Genet. 2015, 92, 53–74.
19. Mattson, M.P.; Longo, V.D.; Harvie, M. Impact of intermittent fasting on health and disease processes.
Ageing Res. Rev. 2017, 39, 46-58.
20. Vance, J.E.; Vance, D.E. Biochemistry of Lipids, Lipoproteins and Membranes. Elsevier 2008, 36, 648.
21. Dąbrowska, M.; Zielińska, A.; Nowak, I. Lipid oxidation products as a potentialhealth and analytical
problem. CHEMIK 2015, 69, 89–94.
22. Toledo, F.W.; Grundler, F.; Bergouignan, A.; Drinda, S.; Michalsen, A. Safety, health improvement and
well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. PLoS ONE
2019, 14, e0209353.
23. Mattson, M.P.; Moehl, K.; Ghena, N.; Schmaedick, M.; Cheng, A. Intermittent metabolic switching,
neuroplasticity and brain health. Nat. Rev. Neurosci. 2018, 19, 63–80.
Nutrients 2019, 11, 673 15 of 18
24. Camandola, S.; Mattson, M.P. Brain metabolism in health, aging, and neurodegeneration. EMBO J. 2017,
36, 1474–1492.
25. Bhutani, S.; Klempel, M.C.; Kroeger, C.M.; Trepanowski, J.F.; Varady, K.A. Alternate day fasting and
endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans.
Obesity (Silver Spring) 2013, 21, 1370–1379.
26. Wilson, R.A.; Deasy, W.; Stathis, C.G.; Hayes, A.; Cooke, M.B. Intermittent Fasting with or without Exercise
Prevents Weight Gain and Improves Lipids in Diet-Induced Obese Mice. Nutrients 2018, 10, 346.
27. Harvie, M.N.; Pegington, M.; Mattson, M.P.; Frystyk ,J.; Dillon, B.; Evans, G.; Cuzick, J.; Jebb, S.A.; Martin,
B.; Cutler, R.G.; et al. The effects of intermittent or continuous energy restriction on weight loss and
metabolic disease risk markers: A randomized trial in young overweight women. Int. J. Obes. (Lond.) 2011,
35, 714–727.
28. Varady, K.A.; Bhutani, S.; Klempel, M.C.; Kroeger, C.M.; Trepanowski, J.F.; Haus, J.M.; Hoddy, K.K.; Calvo
Y.L. Alternate day fasting for weight loss in normal weight and overweight subjects: A randomized
controlled trial. Nutr. J. 2013, 12, 146, doi:10.1186/1475-2891-12-146.
29. Eshghinia, S.; Mohammadzadeh, F. The effects of modified alternate-day fasting diet on weight loss and
CAD risk factors in overweight and obese women. J. Diabetes Metab. Disord. 2013, 12, 4, doi:10.1186/2251-
30. Teng, N.I.M.F.; Shahar, S.; Rajab, N.F.; Manaf, Z.A.; Ngah, W.Z. Improvement of metabolic parameters
inhealthy older adult men following a fasting calorie restriction intervention. Aging Male 2013, 16, 177–183.
31. Harvie, M.N.; Wright, C.; Pegington, M.; McMullan, D.; Mitchell, E.; Martin, B.; Cutler, R.G.; Evans, G.;
Whiteside, S.; Maudsley, S.; et al. The effect of intermittent energy and carbohydrate restriction v. daily
energy restriction on weight loss and metabolic disease risk markers in overweight women. Br. J. Nutr.
2013, 110, 1534–1547.
32. Chowdhury, E.A.; Richardson, J.D.; Holman, G.D.; Tsintzas, K.; Thompson, D.; Betts, J.A. The causal role
of breakfast in energy balance and health: A randomized controlled trial in obese adults. Am. J. Clin. Nutr.
2016, 103, 747–756.
33. Herrington, W.; Lacey, B.; Sherliker, P.; Armitage, J.; Lewington, S. Epidemiology of atherosclerosis and
the possibility of reducing the global burden of atherosclerosis disease. Circ. Res. 2016, 118, 535–546.
34. Lee, Y.T.; Lin, Y.H.; Chan, Y.W.; Li, K.H.; To, O.T.; Yan, B.P.; Liu, T.; Li, G.; Wong, W.T.; Keung, W.; et al.
Mouse models of atherosclerosis: A historical perspective and recent advances. Lipids Health Dis. 2017, 16,
35. Parthasarathy, S.; Quinn, M.T.; Steinberg, D. Is oxidized low density lipoprotein involved in the
recruitment and retention of monocyte/macrophages in the artery wall during the initiation of
atherosclerosis? Basic Life Sci. 1988, 49, 375–380.
36. Braun, M.; Pietsch, P.; Felix, S.B.; Baumann, G. Modulation of intercellular adhesion molecule-1 and
vascular cell adhesion molecule-1 on human coronary smooth muscle cells by cytokines. J. Mol. Cell. Cardiol.
1995, 27, 2571–2579.
37. Sano, H.; Sudo, T.; Yokode, M.; Murayama, T.; Kataoka, H.; Takakura, N.; Nishikawa, S.; Nishikawa, S.I.;
Kita, T. Functional blockade of platelet-derived growth factor receptor-beta but not of receptor-alpha
prevents vascular smooth muscle cell accumulation in fibrous cap lesions in apolipoprotein E-deficient
mice. Circulation 2001, 103, 2955–2960.
38. Kozaki, K.; Kaminski, W.E.; Tang, J.; Hollenbach, S.; Lindahl, P.; Sullivan, C.; Yu, J.C.; Abe, K.; Martin, P.J.;
Ross, R.; et al. Blockade of platelet-derived growth factor or its receptors transiently delays but does not
prevent fibrous cap formation in ApoE null mice. Am. J. Pathol. 2002, 161, 1395–1407.
39. Bays, H.E. “Sick fat,” metabolic disease, and atherosclerosis. Am. J. Med. 2009, 22, 26–37.
40. Aksungar, F.B.; Topkaya, A.E.; Akyildiz, M. Interleukin-6, C-reactive protein and biochemical parameters
during prolonged intermittent fasting. Ann. Nutr. Metab. 2007, 51, 88–95.
41. Kawano, J.; Arora, R. The role of adiponectin in obesity, diabetes, and cardiovascular disease. J. Cardiometab.
Syndr. 2009, 4, 44–49.
42. Bhutani, S.; Klempel, M.C.; Berger, R.A.; Varady, K.A. Improvements in Coronary Heart Disease Risk
Indicators by Alternate-Day Fasting Involve Adipose Tissue Modulations. Obesity 2010, 18, 2152–2159.
43. Cambuli, V.M.; Musiu, M.C.; Incani, M. Assessment of adiponectin and leptin as biomarkers of positive
metabolic outcomes after lifestyle intervention in overweight and obese children. J. Clin. Endocrinol. Metab.
2008, 93, 3051–3057.
Nutrients 2019, 11, 673 16 of 18
44. Achari, A.E.; Jain, S.K. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial
Dysfunction. Int. J. Mol. Sci. 2017, 18, 1321.
45. Ouchi, N.; Kihara, S.; Arita, Y.; Maeda, K.; Kuriyama, H.; Okamoto, Y.; Hotta, K.; Nishida, M.; Takahashi,
K.; Nakamura, T.; et al. Novel modulator for endothelial adhesion molecules: Adipocyte-derived plasma
protein adiponectin. Circulation 1999, 100, 2473–2476.
46. Ouchi, N.; Kihara, S.; Arita, Y.; Okamoto, Y.; Maeda, K.; Kuriyama, H.; Hotta, K.; Nishida, M.; Takahashi,
M.; Muraguchi, M.; et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-
kappaB signaling through a cAMP-dependent pathway. Circulation 2000, 102, 1296–1301.
47. Okamoto, Y.; Folco, E.J.; Minami, M.; Wara, A.K.; Feinberg, M.W.; Sukhova, G.K.; Colvin, R.A.; Kihara, S.;
Funahashi, T.; Luster, A.D.; et al. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands
in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ. Res. 2008, 102, 218–225.
48. Matsuda, M.; Shimomura, I.; Sata, M.; Arita, Y.; Nishida, M.; Maeda, N.; Kumada, M.; Okamoto, Y.;
Nagaretani, H.; Nishizawa, H. Role of adiponectin in preventing vascular stenosis the missing link of
adipo-vascular axis. J. Biol. Chem. 2002, 277, 37487–37491.
49. Wan, R.; Ahmet, I.; Brown, M.; Cheng, A.; Kamimura, N.; Talan, M.; Mattson, M.P. Cardioprotective Effect
of Intermittent Fasting is Associated with an Elevation of Adiponectin Levels in Rats. J. Nutr. Biochem. 2010,
21, 413–417.
50. Sattar, N.; Wannamethee, G.; Sarwar, N.; Chernova, J.; Lawlor, D.A.; Kelly, A.; Wallace, A.M.; Danesh, J.;
Whincup, P.H. Leptin and coronary heart disease: Prospective study and systematic review. J. Am. Coll.
Cardiol. 2009, 53, 167–175.
51. Bowman, J.D.; Bowman, C.D.; Bush, J.E.; Delheij, P.P.; Frankle, C.M.; Gould, C.R.; Haase, D.G.; Knudson,
J.; Mitchell, G.E.; Penttila, S.; et al. Parity nonconservation for neutron resonances in 238U. Phys. Rev. Lett.
1990, 65, 1192–1195.
52. Burnett, M.S.; Lee, C.W.; Kinnaird, T.D.; Stabile, E.; Durrani, S.; Dullum, M.K.; Devaney, J.M.; Fishman, C.;
Stamou, S.; Canos, D.; et al. The potential role of resistin in atherogenesis. Atherosclerosis 2005, 182, 241–248.
53. Schmid, A.; Leszczak, S.; Ober, I.; Karrasch, T.; Schäffler, A. Short-term Regulation of Resistin in vivo by
Oral Lipid Ingestion and in vitro by Fatty Acid Stimulation. Exp. Clin. Endocrinol. Diabetes 2015, 123, 553–
54. Jiang, S.; Park, D.W.; Tadie, J.M.; Gregoire, M.; Deshane, J.; Pittet, J.F.; Abraham, E.; Zmijewski, J.W. Human
resistin promotes neutrophil proinflammatory activation and neutrophil extracellular trap formation and
increases severity of acute lung injury. J. Immunol. 2014, 192, 4795–4803.
55. Hoddy, K.K.; Gibbons, C.; Kroeger, C.M.; Trepanowski, J.F.; Barnosky, A.; Buhtani, S.; Gabel, K.; Finlayson,
G.; Varady, K.A. Changes in hunger and fullness in relation to gut peptides before and after 8 weeks of
alternate day fasting. Clin. Nutr. 2016, 35, 1380–1385.
56. Safavi, E.; Rahbar, A.R. Effect of Intermittent Fasting during Ramadan on Visfatin, Adiponectin and Tumor
Necrotizing Factor-Alpha In Healthy Muslim Individuals J. Fasting Health 2017, 5, 50–55.
57. Alexander, M.R.; Madhur, M.S.; Harrison, D.G.; Dreisbach, A.W.; Riaz, K.; Sander, G.E.; Yang, E.H.
Hypertension: Practice Essentials, Background, Pathophysiology. Cardiology 2018. Available online: (accessed on 1 February 2019).
58. Benjamin, E.J.; Virani, S.S.; Callaway, C.W.; Chamberlain, A.M.; Chang, A.R.; Cheng, S.; Chiuve, S.E.;
Cushman, M.; Delling, F.N.; Deo, R.; et al. Heart Disease and Stroke Statistics—2018 Update, A Report from
the American Heart Association. Circulation 2018, 137, e67–e492.
59. Mager, D.E.; Wan, R.; Brown, M.; Cheng, A.; Wareski, P.; Abernethy, D.R.; Mattson, M.P. Caloric restriction
and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. FASEB
J. 2006, 20, 631–637.
60. Wan, R.; Weigand, L.A.; Bateman, R.; Griffioen, K.; Mendelowitz, D.; Mattson, M.P. Evidence that BDNF
regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability. J.
Neurochem. 2014, 129, 573–580.
61. Yang, B.; Slonimsky, J.D.; Birren, S.J. A rapid switch in sympathetic neurotransmitter release properties
mediated by the p75 receptor. Nat. Neurosci. 2002, 5, 539–545.
62. Wang, J.; Irnaten, M.; Neff, R.A.; Venkatesan, P.; Evans, C.; Loewy, A.D.; Mettenleiter, T.C.; Mendelowitz,
D. Synaptic and neurotransmitter activation of cardiac vagal neurons in the nucleus ambiguus. Ann. N. Y.
Acad. Sci. 2001, 940, 237–246.
Nutrients 2019, 11, 673 17 of 18
63. Erdem, Y.; Ozkan, G.; Ulusoy, S.; Arici, M.; Derici, U.; Sengul, S.; Sindel, S.; Erturk, S. The effect of
intermiitent fasting on blood pressure variability in patients with newly diagnosed hypertension or
prehypertension. J. Am. Soc. Hypertens. 2018, 12, 42–49.
64. Colditz, G.A.; Willett, W.C.; Rotnitzky, A.; Manson, J.E. Weight gain as a risk factor for clinical diabetes
mellitus in women. Ann. Intern. Med. 1995, 122, 481–486.
65. Willett, W.C.; Manson, J.E.; Stampfer, M.J.; Colditz, G.A.; Rosner, B.; Speizer, F.E.; Hennekens, C.H. Weight,
weight change, and coronary heart disease in women. Risk within the ‘normal’ weight range. JAMA 1995,
273, 461–465.
66. Trepanowski, J.F.; Kroeger, C.M.; Barnosky A.; Klempel, M.C.; Bhutani S.; Hoddy, K.K.; Gabel K.; Freels S.;
Rigdon J.; Rood J.; et al. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and
Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Intern.
Med. 2017, 177, 930–938.
67. Schübel, R.; Nattenmüller, J.; Sookthai, D.; Nonnenmacher, T.; Graf, M.E.; Riedl, L.; Schlett, C.L.; von
Stackelberg, O.; Johnson, T.; Nabers, D.; et al. Effects of intermittent and continuous calorie restriction on
bodyweight and metabolism over 50 wk: A randomized controlled trial. Am. J. Clin. Nutr. 2018, 108, 933–
68. Sutton, E.F.; Beyl, R.; Early, K.S.; Cefalu, W.T.; Ravussin, E.; Peterson, C.M. Early Time-Restricted Feeding
Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with
Prediabetes. Cell Metab. 2018, 27, 1212–1221
69. Gotthardt, J.D.; Verpeut, J.L.; Yeomans, B.L.; Yang, J.A.; Yasrebi, A.; Roepke, T.A.; Bello, N.T. Intermittent
Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content,
and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice. Endocrinology 2016, 157,
70. Arnason, T.G.; Bowen, M.W.; Mansell, K.D. Effects of intermittent fasting on health markers in those with
type 2 diabetes: A pilot study. World J. Diabetes 2017, 8, 154–164.
71. Leslie, W.S.; Ford, I.; Sattar, N.; Hollingsworth, K.G.; Adamson, A.; Sniehotta, F.F.; McCombie, L.;
Brosnahan, N.; Ross, H.; Mathers, J.C.; et al. The Diabetes Remission Clinical Trial (DiRECT): Protocol for
a cluster randomised trial. BMC Fam. Pract. 2016, 17, 20.
72. Furmli, S.; Elmasry, R.; Ramos, M.; Fung, J. Therapeutic use of intermittent fasting for people with type 2
diabetes as an alternative to insulin. BMJ Case Rep. 2018, 2018, brc-2017.
73. Sequea, D.A.; Sharma, N.; Arias, E.B.; Cartee, G.D. Calorie restriction enhances insulin-stimulated glucose
uptake and Akt phosphorylation in both fast-twitch and slow-twitch skeletal muscle of 24-month-old rats.
J. Gerontol. A Biol. Sci. Med. Sci. 2012, 67, 1279–1285.
74. Belkacemi, L.; Selselet-Attou, G.; Hupkens, E.; Nguidjoe, E.; Louchami, K.; Sener, A.; Malaisse, W.J.
Intermittent Fasting Modulation of the Diabetic Syndrome in Streptozotocin-Injected Rats. Int. J. Endocrinol.
2012, 2012, 962012.
75. Wei, S.; Han, R.; Zhao, J.; Wang, S.; Huang, M.; Wang, Y.; Chen, Y. Intermittent administration of a fasting-
mimicking diet intervenes in diabetes progression, restores β cells and reconstructs gut microbiota in mice.
Nutr. Metab. (Lond.) 2018, 15, 80.
76. Liu, H.; Javaheri, A.; Godar, R.J.; Murphy, J.; Ma, X.; Rohatgi, N.; Mahadevan, J.; Hyrc, K.; Saftig, P.;
Marshall, C.; et al. Intermittent fasting preserves beta-cell mass in obesity-induced diabetes via the
autophagy-lysosome pathway. Autophagy 2017, 13, 1952–1968.
77. Zhao, L.R.; Willing, A. Enhancing endogenous capacity to repair a stroke-damaged brain: An evolving field
for stroke research. Prog. Neurobiol. 2018, 163-164, 5–26.
78. Fann, D.Y.; Ng, G.Y.; Poh, L.; Arumugam, T.V. Positive effects of intermittent fasting in ischemic stroke.
Exp. Gerontol. 2017, 89, 93–102.
79. Wang, Z.; Li, L.; Zhao, H.; Peng, S.; Zuo, Z. Chronic high fat diet induces cardiac hypertrophy and fibrosis
in mice. Metabolism 2015, 64, 917–925.
80. Scicchitano, P.; Cameli, M.; Maiello, M.; Modesti, P.A.; Muiesan, M.L.; Novo, S.; Palmiero, P.; Sergio Saba,
P.; Pedrinelli, R.; Ciccone, M.M. Nutraceuticals and dyslipidaemia: Beyondthe commontherapeutics. J.
Funct. Food 2014, 6, 11–32.
81. Giordano, P.; Scicchitano, P.; Locorotondo, M.; Mandurino, C.; Ricci, G.; Carbonara, S.; Gesualdo, M.; Zito,
A.; Dachille, A.; Caputo, P.; et al. Carotenoids and cardiovascular risk. Curr. Pharm. Des. 2012, 18, 5577–
Nutrients 2019, 11, 673 18 of 18
82. Wiciński, M.; Malinowski, B.; Węclewicz, M.M.; Grześk, E.; Grześk, G. Resveratrol increases serum BDNF
concentrations and reduces vascular smooth muscle cells contractility via a NOS-3-independent
mechanism. Biomed. Res. Int. 2017, 2017, 9202954.
83. Wiciński, M.; Malinowski, B.; Węclewicz, M.M.; Grześk, E.; Grześk, G. Anti-athergoenic properties of
resveratrol: 4-week resveratrol administration associated with serum concentrations of SIRT1, adiponectin,
S100A8/9 and VSMCs contractility in a rat model. Exp. Ther. Med. 2017, 13, 2071–2078.
84. Chen, Q.; Wang, E.; Ma, L.; Zhai, P. Dietary resveratrol increases the expression of hepatic 7a-hydroxylase
and ameliorates hypercholesterolemia in high-fat fed C57BL/6J mice. Lipids Health Dis. 2012, 11, 56.
85. Sahebkar, A. Effects of resveratrol supplementation on plasma lipids: A systematic review and meta-
analysis of randomized controlled trials. Nutr. Rev. 2013, 71, 822–835.
86. Wu, C.H.; Chen, S.C.; Ou, T.T.; Chyau, C.C.; Chang, Y.C.; Wang, C.J. Mulberry leaf polyphenol extracts
reduced hepatic lipid accumulation involving regulation of adenosine monophosphate activated protein
kinase and lipogenic enzymes. J. Funct. Foods 2013, 5, 1620–1632.
87. Jin, D.; Xua, Y.; Meia, X. Antiobesity and lipid lowering effects of theaflavins on high-fat diet induced obese
rats. J. Funct. Foods 2013, 5, 1142–1150.
88. Gunathilake, K.D.P.P.; Wang, Y.; Vasantha Rupasinghea, H.P. Hypocholesterolemic and hypotensive
effects of a fruitbased functional beverage in spontaneously hypertensive rats fed with cholesterol-rich diet.
J. Funct. Foods 2013, 5, 1392–1401.
89. Ciccone, M.M.; Scicchitano, P.; Gesualdo, M.; Zito, A.; Carbonara, S.; Ricci, G.; Cortese, F.; Giordano, P. The
role of omega-3 polyunsaturated fatty acids supplementation in childhood: A review. Recent Patents
Cardiovasc. Drug Discov. 2013, 8, 42–55.
90. Kris-Etherton, P.M.; Harris, W.S.; Appel, L.J. American Heart Association Nutrition Committee. Fish
consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002, 106, 2747–2757.
91. Schmidt, S.; Willers, J.; Stahl, F.; Dardano, A.; Penno, G.; Del Prato Mutz, K.O.; Scheper, T.; Hahn, A.;
Schuchardt, J.P. Regulation of lipid metabolism-related gene expression in whole blood cells of normo- and
dyslipidemic men after fish oil supplementation. Lipids Health Dis. 2012, 11, 172.
92. Zhao, J.F.; Ching, L.C.; Huang, Y.C.; Chen, C.Y.; Chiang, A.N.; Kou, Y.R.; Shyue, S.K.; Lee, T.S. Molecular
mechanism of curcumin on the suppression of cholesterol accumulation in macrophage foam cells and
atherosclerosis. Mol. Nutr. Food Res. 2012, 56, 691–701.
93. Rahimi-Ardabili, B.; Argani, H.; Ghorbanihaghjo, A.; Rashtchizadeh, N.; Naghavi-Behzad, M.; Ghorashi,
S.; Nezami, N. Paraoxonase enzyme activity is enhanced by zinc supplementation in hemodialysis patients.
Renal Failure 2012, 34, 1123–1128.
94. Li, H.L.; Liu, D.P.; Liang, C.C. Paraoxonase gene polymorphisms, oxidative stress, and diseases. J. Mol.
Med. (Berlin) 2003, 81, 766–779.
95. Bronwen, M.; Mattson, M.P.; Maudsleya, S. Caloric restriction and intermittent fasting: Two potential diets
for successful brain aging. Ageing Res. Rev. 2006, 5, 332–353.
96. Beshyah, S.A.; Hassanein, M.; Ahmedani, M.Y.; Shaikh, S.; Ba-Essa, E.M.; Megallaa, M.H.; Afandi, B.;
Ibrahim, F.; Al-Muzaffar, T. Diabetic Hypoglycaemia during Ramadan Fasting: A Trans-National
Observational Real-World Study. Diabetes Res. Clin. Pract. 2019, 18, 31843–31846.
97. Dardano A.; Penno G.; Del Prato S.; Miccoli R. Optimal therapy of type 2 diabetes: A controversial
challenge. Aging (Albany NY) 2014, 6, 187–206.
98. Miller, M.E.; Williamson, J.D.; Gerstein, H.C.; Byington, R.P.; Cushman, W.C.; Ginsberg, H.N.; Ambrosius,
W.T.; Lovato, L.; Applegate, W.B.; ACCORD Investigators. Effects of randomization to intensive glucose
control on adverse events, cardiovascular disease, and mortality in older versus younger adults in the
ACCORD Trial. Diabetes Care 2014, 37, 634–643.
99. Ganesan, K.; Habboush, Y.; Sultan, S. Intermittent Fasting: The Choice for a Healthier Lifestyle. Cureus
2018, 10, e2947.
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
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... Low carbohydrate/ ketogenic diet Improvement of the metabolic syndrome and beneficial effect on all common comorbidities/risk factors in the PAD population. This dietary model can be adopted for short periods alternating with the MD [44, 384,385] Intermittent fasting Correction of dysbiosis with a reduction in inflammation; prevention of atherosclerotic plaque vulnerability by modulating local inflammation and change in the lipid core of the plaque of peripheral arteries; improvement of liver function and glucose/lipid metabolism with consequent secondary prevention of CV risk; concerns about osteoporosis and hypoglycemia in diabetic patients with PAD [77,[386][387][388][389][390] ...
... Based on the current evidence, IF could ensure a reduction in the serum levels of triglycerides and LDL-c with an increase in HDL-c, with a consequent decrease in cardiovascular risk [72,73]. Part of the benefit derives from the amount of body weight loss and the qualitative change in body mass, with a ripple effect on the respiratory exchange ratio, lipid profile and metabolism, regardless of concomitant physical activity and eating habits [53, [74][75][76][77][78][79]. ...
... The progression of atherosclerotic plaques leading to the narrowing of the arteries relies on endothelial dysfunction and the long-term exposure to oxidative stress. The proinflammatory processes occurring in atherosclerotic plaques appear to be influenced by the metabolic effects of intermittent fasting [77]. The cytokine load promoted by foam cells exposed to oxidized LDL is markedly reduced in patients during intermittent fasting, [587][588][589][590]. ...
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Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE.
... El sobrepeso y la obesidad, clasificados como Índice de Masa Corporal (IMC) mayor o igual a 25 y 30 respectivamente, se deben a un exceso de acumulación de grasa almacenada en el tejido adiposo. Esta patología surge del desequilibrio energético: consumir más energía, kilocalorías (kcal) de la que se gasta; de ahí que la mayor parte de los enfoques para el control de peso se centran en reducir la ingesta de energía a través de la restricción calórica y el aumento del gasto energético a través de la actividad física 10 . La OMS estima que hoy en día, más de 1500 millones de adultos en todo el mundo tienen sobrepeso y otros 600 millones son obesos 11 . ...
... En consecuencia, el control eficaz del peso es un desafío y, aunque existe una enorme cantidad de programas de pérdida de peso disponibles, no todos están evaluados de manera exhaustiva; y muchos intentos de pérdida de peso dan como resultado una recuperación de peso y resultados deficientes a largo plazo 13 . Por lo tanto, es de vital importancia revisar la eficacia de los patrones dietéticos para apoyar un enfoque basado en la evidencia para el control del peso y el riesgo cardiovascular a largo plazo 10 . ...
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ID ID ID ID Resumen Introducción: las enfermedades cardiovasculares no sólo son la primera causa de muerte con un 30% de todas ellas en el mundo, sino que el importante aumento de su incidencia en estos últimos años las sitúa en una urgencia sanitaria. Estas patologías están muy relacionadas con patrones alimentarios poco saludables (consumo intensivo de sodio, azúcares, grasas saturadas; y un bajo consumo de frutas y verduras, cereales, fibra, legumbres, pescado y frutos secos). Un patrón dietético adecuado y ajustado individualmente a las características clínicas de cada paciente pueden ayudarnos a reducir tanto el peso corporal como el riesgo cardiovascular. Objetivo: Analizar y comparar la eficacia de los principales patrones dietéticos en la reducción del riesgo cardiovascular. Resultados: La dieta mediterránea sigue siendo el patrón con mayor evidencia y mejores resultados sobre la reducción de dicho riesgo cardiovascular y su mortalidad. Sin embargo, la dieta DASH es una buena alternativa sobre todo para pacientes hipertensos, a su vez, la dieta vegetariana ha demostrado multitud de beneficios cardiovasculares, presentando escasas desventajas. Otra alternativa más compleja pero muy de moda actualmente es la dieta cetogénica, que todavía no cuenta con suficiente respaldo científico en la reducción del riesgo cardiovascular. Conclusiones: Realizar un adecuado patrón dietético es la medida más importante para prevenir la primera causa de muerte en el mundo, para ello disponemos de varios patrones alimentarios entre los que destaca la dieta mediterránea.
... Catenacci et al. 24 (2016) Stekovic et al. 25 (2019) Trepanowski et al. 26 (2017) Varady et al. 27 (2013) Chow et al. 28 (2020) Domaszewski, et al. 29 (2020) Colesterol total (mg/dL) Se observa que la presión arterial sistólica y diastólica disminuye, esto podría explicarse pues se plantea que una disminución del peso corporal influye en la disminución de la presión arterial 37,38 , esto a su vez, suprime la producción de catecolaminas reduciendo el tono simpático, aumentando la excreción renal de Na y la sensibilidad a la insulina 33,39 . ...
... Lo mismo sucede con perímetro de cintura que, a pesar de ser una variable de interés como factor de riesgo cardiovascular, no se informó como tal en ninguno de los seis artículos incluidos. Por último, en relación con efectos adversos solo tres estudios informaron 36,37,39 y uno de ellos informó síntomas 39 . Además, evidenciamos que la mayoría presentaban riesgo de sesgo por posible falta de cegamiento de los evaluadores. ...
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Intermittent fasting has become popular as an alternative strategy for weight control and the reduction of some biochemical parameters. The purpose of this systematic review (SR) was to evaluate the effectiveness of intermittent fasting in two protocols: intermittent days fasting (ADA) and time-restricted fasting (ART), on lipid profile, body composition and blood pressure among adults. Methods: SR based on randomized controlled trials consulted in the following databases: Web of Science, Scopus, Library Cochrane, Clinical Trials, Proquest and PubMed. Adults over 18 years of age with any nutritional status were studied. The intervention corresponded to intermittent fasting of at least 16 hours. Risk of bias were assessed according to the Cochrane collaboration. Results: Six clinical trials were analyzed, finding that the ADA protocol, present in four of them, generated changes in the variables: triglycerides, c-HDL, c-LDL, total cholesterol, weight, lean mass, fat mass and systolic blood pressure, while the ART protocol, present in the remaining two, caused changes in the variables: weight, fat mass, lean mass, triglycerides, total cholesterol, c-LDL, c-HDL and glycemia. Conclusion: The available evidence with clinical trials allows us to suggest that the ADA and ART protocols can be an alternative diet for adults. However, caloric adjustment and adequate education on healthy lifestyles show similar results. Notwithstanding this, intermittent fasting may be an alternative for those who find it difficult to follow a dietary pattern with daily caloric restriction.
... It is one of the costliest diseases for governments and healthcare systems (up to USD 320 billion/year) [2]. In 2019, according to a report from the World Health Organization (WHO), 17.9 million people died from CD, including clinical disorders of the heart and blood vessels [3]. There are several risk factors for CD, such as high blood pressure, diabetes mellitus, smoking, dyslipidemia, and being overweight/obesity [4,5]. ...
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Angiotensin-converting enzyme (ACE) inhibitors are one of the most active classes for cardiovascular diseases and hypertension treatment. In this regard, developing active and non-toxic ACE inhibitors is still a continuous challenge. Furthermore, the literature survey shows that oxidative stress plays a significant role in the development of hypertension. Herein, glutathione’s molecular structure and supramolecular arrangements are evaluated as a potential ACE inhibitor. The tripeptide molecular modeling by density functional theory, the electronic structure by the frontier molecular orbitals, and the molecular electrostatic potential map to understand the biochemical processes inside the cell were analyzed. The supramolecular arrangements were studied by Hirshfeld surfaces, quantum theory of atoms in molecules, and natural bond orbital analyses. They showed distinct patterns of intermolecular interactions in each polymorph, as well as distinct stabilizations of these. Additionally, the molecular docking study presented the interactions between the active site residues of the ACE and glutathione via seven hydrogen bonds. The pharmacophore design indicated that the hydrogen bond acceptors are necessary for the interaction of this ligand with the binding site. The results provide useful information for the development of GSH analogs with higher ACE inhibitor activity.
The disparity in the free radical generation and the production of antioxidants to counteract its effect is known as oxidative stress. Oxidative stress causes damage to the macromolecules such as lipids, carbohydrates, proteins, and DNA and RNA. The oxidative damage to the cellular components leads to a process of aging and various age-associated disorders. The literature survey for this review was done using PubMed, Google Scholar, and Science Direct. The papers showing the studies related to aging and age-associated disorders have been selected for reviewing this paper. Ellagic acid has been used as the keyword, and more emphasis has been put on papers from the last 10 years. However, some papers with significant studies prior to 10 years have also been considered. Almost 250 papers have been studied for reviewing this paper, and about 135 papers have been cited. Ellagic acid (EA) is present in high quantities in pomegranate and various types of berries. It is known to possess the antioxidant potential and protects from the harmful effects of free radicals. Various studies have shown its effect to protect cardiovascular, neurodegenerative, cancer, and diabetes. The present review focuses on the protective effect of ellagic acid in age-associated disorders. The effect of EA has been studied in various chronic disorders but the scope of this review is limited to cancer, diabetes, cardiovascular and neurodegenerative disorders. All the disease aspects have not been addressed in this particular review.
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Experimental trials in organisms ranging from yeast to humans have shown that various forms of reducing food intake (caloric restriction) appear to increase both overall and healthy lifespan, delaying the onset of disease and slowing the progression of biomarkers of aging. The gut microbiota is considered one of the key environmental factors strongly contributing to the regulation of host health. Perturbations in the composition and activity of the gut microbiome are thought to be involved in the emergence of multiple diseases. Indeed, many studies investigating gut microbiota have been performed and have shown strong associations between specific microorganisms and metabolic diseases including overweight, obesity, and type 2 diabetes mellitus as well as specific gastrointestinal disorders, neurodegenerative diseases, and even cancer. Dietary interventions known to reduce inflammation and improve metabolic health are potentiated by prior fasting. Inversely, birth weight differential host oxidative phosphorylation response to fasting implies epigenetic control of some of its effector pathways. There is substantial evidence for the efficacy of fasting in improving insulin signaling and blood glucose control, and in reducing inflammation, conditions for which, additionally, the gut microbiota has been identified as a site of both risk and protective factors. Accordingly, human gut microbiota, both in symbiont and pathobiont roles, have been proposed to impact and mediate some health benefits of fasting and could potentially affect many of these diseases. While results from small-N studies diverge, fasting consistently enriches widely recognized anti-inflammatory gut commensals such as Faecalibacterium and other short-chain fatty acid producers, which likely mediates some of its health effects through immune system and barrier function impact.
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Circadian rhythm, an innate 24-h biological clock, regulates several mammalian physiological activities anticipating daily environmental variations and optimizing available energetic resources. The circadian machinery is a complex neuronal and endocrinological network primarily organized into a central clock, suprachiasmatic nucleus (SCN), and peripheral clocks. Several small molecules generate daily circadian fluctuations ensuring inter-organ communication and coordination between external stimuli, i.e., light, food, and exercise, and body metabolism. As an orchestra, this complex network can be out of tone. Circadian disruption is often associated with obesity development and, above all, with diabetes and cardiovascular disease onset. Moreover, accumulating data highlight a bidirectional relationship between circadian misalignment and cardiometabolic disease severity. Food intake abnormalities, especially timing and composition of meal, are crucial cause of circadian disruption, but evidence from preclinical and clinical studies has shown that food could represent a unique therapeutic approach to promote circadian resynchronization. In this review, we briefly summarize the structure of circadian system and discuss the role playing by different molecules [from leptin to ghrelin, incretins, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF15)] to guarantee circadian homeostasis. Based on the recent data, we discuss the innovative nutritional interventions aimed at circadian re-synchronization and, consequently, improvement of cardiometabolic health.
Psoriasis is an immune‐mediated inflammatory skin disease affecting approximately 2% of the UK population. Its pathogenesis is suggested to be an outcome of genetic and environmental interplay. People with psoriasis have an increased likelihood of developing other conditions such as type 2 diabetes and cardiovascular disease. Systemic inflammation is hypothesised to be the common link between psoriasis and cardio‐metabolic diseases. Emerging evidence shows diet as a potential therapeutic adjunct in the management of psoriasis. The Diet and Psoriasis Project (DIEPP) aims to investigate whether dietary factors are related to psoriasis severity by conducting an observational study followed by a dietary intervention trial, to assess the effect of the Mediterranean diet (MedD) and time‐restricted eating (TRE) on psoriasis. This review article will explore the potential mechanisms by which the MedD and TRE may exert protective effects on psoriasis, evaluate the current evidence, and outline the design of the DIEPP. Given the early‐stage evidence, we hope to be able to build knowledge to derive medically approved dietary recommendations and contribute to the research gaps exploring the role of diet and psoriasis.
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Only few studies document longer periods of fasting in large cohorts including non-obese participants. The aim of this study was to document prospectively the safety and any changes in basic health and well-being indicators during Buchinger periodic fasting within a specialised clinic. In a one-year observational study 1422 subjects participated in a fasting program consisting of fasting periods of between 4 and 21 days. Subjects were grouped in fasting period lengths of 5, 10, 15 and 20±2 days. The participants fasted according to the Buchinger guidelines with a daily caloric intake of 200–250 kcal accompanied by a moderate-intensity lifestyle program. Clinical parameters as well as adverse effects and well-being were documented daily. Blood examinations before and at the end of the fasting period complemented the pre-post analysis using mixed-effects linear models. Significant reductions in weight, abdominal circumference and blood pressure were observed in the whole group (each p<0.001). A beneficial modulating effect of fasting on blood lipids, glucoregulation and further general health-related blood parameters was shown. In all groups, fasting led to a decrease in blood glucose levels to low norm range and to an increase in ketone bodies levels (each p<0.001), documenting the metabolic switch. An increase in physical and emotional well-being (each p<0.001) and an absence of hunger feeling in 93.2% of the subjects supported the feasibility of prolonged fasting. Among the 404 subjects with pre-existing health-complaints, 341 (84.4%) reported an improvement. Adverse effects were reported in less than 1% of the participants. The results from 1422 subjects showed for the first time that Buchinger periodic fasting lasting from 4 to 21 days is safe and well tolerated. It led to enhancement of emotional and physical well-being and improvements in relevant cardiovascular and general risk factors, as well as subjective health complaints.
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Fasting and especially intermittent fasting have been shown to be an effective intervention in many diseases, such as obesity and diabetes. The fasting-mimicking diet (FMD) has recently been found to ameliorate metabolic disorders. To investigate the effect of a new type of low-protein low-carbohydrate FMD on diabetes, we tested an FMD in db/db mice, a genetic model of type 2 diabetes. The diet was administered every other week for a total of 8 weeks. The intermittent FMD normalized blood glucose levels in db/db mice, with significant improvements in insulin sensitivity and β cell function. The FMD also reduced hepatic steatosis in the mice. Deterioration of pancreatic islets and the loss of β cells in the diabetic mice were prevented by the FMD. The expression of β cell progenitor marker Ngn3 was increased by the FMD. In addition, the FMD led to the reconstruction of gut microbiota. Intermittent application of the FMD increased the genera of Parabacteroides and Blautia while reducing Prevotellaceae, Alistipes and Ruminococcaceae. The changes in these bacteria were also correlated with the fasting blood glucose levels of the mice. Furthermore, intermittent FMD was able to reduce fasting blood glucose level and increase β cells in STZ-induced type 1 diabetic mouse model. In conclusion, our study provides evidence that the intermittent application of an FMD is able to effectively intervene in the progression of diabetes in mice. Electronic supplementary material The online version of this article (10.1186/s12986-018-0318-3) contains supplementary material, which is available to authorized users.
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This case series documents three patients referred to the Intensive Dietary Management clinic in Toronto, Canada, for insulin-dependent type 2 diabetes. It demonstrates the effectiveness of therapeutic fasting to reverse their insulin resistance, resulting in cessation of insulin therapy while maintaining control of their blood sugars. In addition, these patients were also able to lose significant amounts of body weight, reduce their waist circumference and also reduce their glycated haemoglobin level.
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Obesity is a worldwide epidemic due to the availability of many unhealthy food options and limited physical exercise. Restriction of the daily food intake results in weight loss, which is also associated with better health outcomes including triglycerides, total cholesterol, low-density lipoprotein cholesterol, blood pressure, glucose, insulin, and C-reactive protein. Our aim is to briefly discuss the effects of intermittent fasting on weight and other biochemical markers mentioned previously. The study is designed as a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. To assess the effectiveness of intermittent fasting, related studies were reviewed between 2000 and 2018 and 815 studies were identified. Only four articles met the preset inclusion and exclusion criteria. All four studies have shown a significant decrease in fat mass with P-values <0.01. It was also noted that some biochemical markers were significantly reduced such as the reduction in low-density lipoprotein and triglyceride with P-values < 0.05. Other biochemical markers had inconsistent results. Based on the qualitative analysis, intermittent fasting was found to be efficient in reducing weight, irrespective of the body mass index. Further studies are needed to assess the ability to maintain the lost weight without regaining it and the long-term effects of such dietary changes.
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Intermittent fasting (IF) and high intensity interval training (HIIT) are effective lifestyle interventions for improving body composition and overall health. However, the long-term effects of IF and potential synergistic effects of combining IF with exercise are unclear. The purpose of the study was to investigate the long-term effects of IF, with or without HIIT, on body composition and markers of metabolic health in diet-induced obese mice. In a randosmised, controlled design, 8-week-old C57BL/6 mice (males (n = 39) and females (n = 49)) were fed a high fat (HF) and sugar (S) water diet (30% (w/v)) for 24-weeks but were separated into five groups at 12-weeks: (1) ‘obese’ baseline control (OBC); (2) no intervention (CON); (3) intermittent fasting (IF); (4) high intensity intermittent exercise (HIIT) and (5) combination of dietary and exercise intervention (IF + HIIT). Body composition, strength and blood variables were measured at 0, 10 and/or 12-weeks. Intermittent fasting with or without HIIT resulted in significantly less weight gain, fat mass accumulation and reduced serum low density lipoproteins (LDL) levels compared to HIIT and CON male mice (p < 0.05). The results suggest that IF, with or without HIIT, can be an effective strategy for weight gain prevention despite concurrently consuming a high fat and sugar diet.
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Stroke represents a severe medical condition that causes stroke survivors to suffer from long-term and even lifelong disability. Over the past several decades, a vast majority of stroke research targets neuroprotection in the acute phase, while little work has been done to enhance stroke recovery at the later stage. Through reviewing current understanding of brain plasticity, stroke pathology, and emerging preclinical and clinical restorative approaches, this review aims to provide new insights to advance the research field for stroke recovery. Lifelong brain plasticity offers the long-lasting possibility to repair a stroke-damaged brain. Stroke impairs the structural and functional integrity of entire brain networks; the restorative approaches containing multi-components have great potential to maximize stroke recovery by rebuilding and normalizing the stroke-disrupted entire brain networks and brain functioning. The restorative window for stroke recovery is much longer than previously thought. The optimal time for brain repair appears to be at later stage of stroke rather than the earlier stage. It is expected that these new insights will advance our understanding of stroke recovery and assist in developing the next generation of restorative approaches for enhancing brain repair after stroke.
Objectives To describe the risk of hypoglycaemia during Ramadan and determine its risk factors, and the impact of hypoglycaemia on patients' behaviour. Methods A cross-sectional multi-country observational study, with data captured within 6 weeks after Ramadan 2015. Patients' and disease characteristics and its management, the risk of hypoglycaemia and patients' response to hypoglycaemia were recorded Results A cohort of 1759 patients; majority with type 2 diabetes mellitus from North Africa, Arabian Gulf, Saudi Arabia, and the Indian subcontinent. Hypoglycaemia was reported by 290 patients (16.8%); particularly affecting type 1 diabetes patients and in insulin-treated patients in general. Age was significantly younger in the hypoglycaemia group (P<0.001). The commonest responses were reducing the dose or frequency of medications (42%), attending primary care providers (24.5%) or increasing monitoring (20.7%). Fasting was interrupted by 67% only of those who experienced hypoglycaemia and recourse to emergency services was pursued by less than a quarter of patients with hypoglycaemia. The country-wise analysis of the rates of hypoglycaemia was greatest in Egypt (51.3%) and lowest in Pakistan (3.5%). Conclusions Hypoglycaemia is a significant complication of fasting during Ramadan. It may be predicted by type of diabetes, and use of insulin. Patients’ responses are varied and call for more formal pre-Ramadan education
Background: Although preliminary evidence suggests that intermittent calorie restriction (ICR) exerts stronger effects on metabolic parameters, which may link obesity and major chronic diseases, compared with continuous calorie restriction (CCR), there is a lack of well-powered intervention studies. Objective: We conducted a randomized controlled trial to test whether ICR, operationalized as the "5:2 diet," has stronger effects on adipose tissue gene expression, anthropometric and body composition measures, and circulating metabolic biomarkers than CCR and a control regimen. Design: One hundred and fifty overweight and obese nonsmokers [body mass index (kg/m2) ≥25 to <40, 50% women], aged 35-65 y, were randomly assigned to an ICR group (5 d without energy restriction and 2 d with 75% energy deficit, net weekly energy deficit ∼20%), a CCR group (daily energy deficit ∼20%), or a control group (no advice to restrict energy) and participated in a 12-wk intervention phase, a 12-wk maintenance phase, and a 26-wk follow-up phase. Results: Loge relative weight change over the intervention phase was -7.1% ± 0.7% (mean ± SEM) with ICR, -5.2% ± 0.6% with CCR, and -3.3% ± 0.6% with the control regimen (Poverall < 0.001, PICR vs. CCR = 0.053). Despite slightly greater weight loss with ICR than with CCR, there were no significant differences between the groups in the expression of 82 preselected genes in adipose tissue implicated in pathways linking obesity to chronic diseases. At the final follow-up assessment (week 50), weight loss was -5.2% ± 1.2% with ICR, -4.9% ± 1.1% with CCR, and -1.7% ± 0.8% with the control regimen (Poverall = 0.01, PICR vs. CCR = 0.89). These effects were paralleled by proportional changes in visceral and subcutaneous adipose tissue volumes. There were no significant differences between ICR and CCR regarding various circulating metabolic biomarkers. Conclusion: Our results on the effects of the "5:2 diet" indicate that ICR may be equivalent but not superior to CCR for weight reduction and prevention of metabolic diseases. This trial was registered at as NCT02449148.
Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Men with prediabetes were randomized to eTRF (6-hr feeding period, with dinner before 3 p.m.) or a control schedule (12-hr feeding period) for 5 weeks and later crossed over to the other schedule. eTRF improved insulin sensitivity, β cell responsiveness, blood pressure, oxidative stress, and appetite. We demonstrate for the first time in humans that eTRF improves some aspects of cardiometabolic health and that IF's effects are not solely due to weight loss.
Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together in a single document the most up-to-date statistics related to heart disease, stroke, and the cardiovascular risk factors listed in the AHA's My Life Check - Life's Simple 7 (Figure¹), which include core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure [BP], and glucose control) that contribute to cardiovascular health. The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions. Cardiovascular disease (CVD) and stroke produce immense health and economic burdens in the United States and globally. The Update also presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease [CHD], heart failure [HF], valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). Since 2007, the annual versions of the Statistical Update have been cited >20 000 times in the literature. From January to July 2017 alone, the 2017 Statistical Update was accessed >106 500 times. Each annual version of the Statistical Update undergoes revisions to include the newest nationally representative data, add additional relevant published scientific findings, remove older information, add new sections or chapters, and increase the number of ways to access and use the assembled information. This year-long process, which begins as soon as the previous Statistical Update is published, is performed by the AHA Statistics Committee faculty volunteers and staff and government agency partners. This year's edition includes new data on the monitoring and benefits of cardiovascular health in the population, new metrics to assess and monitor healthy diets, new information on stroke in young adults, an enhanced focus on underserved and minority populations, a substantively expanded focus on the global burden of CVD, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA's 2020 Impact Goals. Below are a few highlights from this year's Update.