کافئین

A high-fat diet (HFD) contributes to obesity and cardiac damage. This study investigated the protective effects of eight weeks of caffeine supplementation (CAF) on HFD-induced changes in the expression of BAX, BCL2, the BAX/BCL2 ratio, and caspase 3 in the heart tissue of male Wistar rats.

Thirty-two male Wistar rats (8 weeks old, 181 ± 15 grams) were randomly assigned to one of four groups (n=8 per group): normal diet (ND), normal diet with caffeine (ND+CAF), high-fat diet (HFD), and high-fat diet with caffeine (HFD+CAF). Rats had free access to water and their assigned diet. The caffeine supplement was administered via gavage at 6 mg/kg/day. After eight weeks, heart tissue was collected, and the protein expression of apoptosis markers was measured using Western blotting. Data were analyzed using one-way ANOVA followed by Tukey’s post-hoc test (GraphPad Prism).

Compared to the ND and ND+CAF groups, the HFD and HFD+CAF groups showed significantly higher BAX expression (P≤0.001). BCL2 expression was significantly elevated in the ND+CAF and HFD+CAF groups compared to the ND and HFD groups (P≤0.001). The BAX/BCL2 ratio was lower in the ND+CAF and HFD+CAF groups compared to the ND and HFD groups (P ≤ 0.001). No significant differences were observed in caspase 3 expression (P≥0.05).

These findings suggest that caffeine supplementation may mitigate HFD-induced alterations in the expression of specific apoptotic proteins in rat heart tissue

The Production Process Of Teas And Their Brewing Conditions Play A Significant Role In The Properties And Compounds Found In Various Types Of Tea. In This Research, The Effect Of Tea Brewing Time On The Amount Of Total Phenolic Compounds And Antioxidant Activity And Caffeine Of Extracts From Four Types Of Tea Was Investigated. 

 All Kinds Of Black, White, Green And Matcha Teas Were Brewed In Two Times Of 10 Minutes And 30 Minutes And A Constant Temperature Of 90 Degrees Celsius, Then The Amount Of Total Phenolic Compounds Was Determined By Folin-Ciocalteu Method, Antioxidant Activity By Two Methods. DPPH, FRAP And The Amount Of Caffeine Were Measured And Compared With Each Other Using A Spectrophotometer.

In 10 Minutes Of Brewing The Examined Teas, The Highest Amount Of Total Phenolic Compounds (360.10 G/L Of Gallic Acid) And The Highest Amount Of Antioxidant Properties Obtained From The FRAP Test (1681.36 µm Feso4) And The Highest Amount Of Caffeine ( 25.59 Mg/L Of Pure Caffeine) Belonged To Matcha Tea And The Highest IC50 Obtained From The DPPH Test (3.98 G/L) Belonged To Black Teas. In 30 Minutes Of Tea Brewing, The Highest Amount Of Total Phenolic Compounds (379.87 Mg/L Of Gallic Acid) Belongs To Chinese Green Tea, The Highest Amount Of Antioxidant Properties Obtained From The FRAP Test (1742.55 µm Feso4) Belongs To Iranian Green Tea, The Highest Amount Of IC50 (2.78 G/L) Belonged To Black Tea, And The Highest Amount Of Caffeine (27.01 Mg/L Of Pure Caffeine) Belonged To C.T.C. Black Tea.

The Overall Conclusion Showed That The Type Of Tea And Its Brewing Conditions Have A Significant Effect On The Amount Of Bioactive Compounds In The Tea Extract Consumed.

One of the most common problems in newborns is apnea of prematurity. Given the importance of preventing apnea in very premature infants, the present study was designed and conducted to investigate the preventive effect of caffeine on reducing the frequency of apnea events in very premature infants.

This randomized, double-blind, controlled clinical trial was conducted on premature infants hospitalized in the neonatal intensive care unit of Shahid Motahari Hospital in Urmia. Infants were randomly divided into two intervention and control groups. The intervention group received intravenous caffeine at an initial dose of 20 mg/kg and a maintenance dose of 5 mg/kg for 14 days. In contrast, the control group received an equal volume of normal saline intravenously for the same period. Apnea events, cyanosis attacks, and bradycardia were recorded by the researchers in a standard checklist.

Of the 50 infants in each group, 2% of the caffeine and 4% of the control group required prolonged oxygen therapy, respectively. Also, 6% of the caffeine group and 4% of the control group experienced intraventricular hemorrhage. In addition, 4% of the caffeine group and 2% of the control group required surgery to close the patent ductus arteriosus, and 14% of the caffeine group and 18% of the control group experienced apneic events. However, there was no statistically significant difference between the two groups regarding the incidence of apneic events (P = 0.58). Ultimately, 20% of the caffeine group and 14% of the control group died.

Although the findings of the present study were not statistically significant, they indicate a decrease in the frequency of apnea events in the group of premature infants receiving caffeine compared to the control group.

The aim of this study was to investigate the effect of acute administration of caffeine and adenosine alone or in combination with celecoxib (a cyclooxygenase-2 inhibitor) on the seizure threshold induced by pentylenetetrazole (PTZ).

Male NMRI mice (30-25 g, 10 per group) were divided into groups of 10, control and experimental groups receiving adenosine (25, 50, and 100 mg/kg), caffeine (10, 40, 80, and 100 mg/kg), celecoxib (2.5, 5, and 10 mg/kg) and combination of celecoxib with adenosine or caffeine. The threshold doses for clonic and tonic seizures were measured by intravenous infusion of PTZ.

Adenosine at doses of 50 and 100 mg/kg showed anticonvulsant effects. Caffeine at the doses of 10, 40, 80, and 100 mg/kg significantly reduced the tonic seizure threshold while only at the doses of 10 and 40 mg/kg reduced the clonic seizure threshold. Celecoxib had anticonvulsant effects only at the dose of 10 mg/kg. The combination of celecoxib with adenosine enhanced the anticonvulsant effect of adenosine. In addition, the combination of celecoxib with caffeine reduced the proconvulsant effects of caffeine to some extent.

The combination of celecoxib with caffeine abolished some of the convulsant effects of caffeine and potentiated the anticonvulsant effect of adenosine, suggesting that part of the convulsant effect of caffeine and anticonvulsant effect of adenosine was through modulation of the cyclooxygenase-2 pathway.

Type 2 diabetes, as the most common metabolic disease, is a chronic and progressive disorder that causes permanent complications and increases cardiovascular diseases, brain vessels, peripheral vessels, and mortality in affected people. This study, therefore, aimed to investigate the effect of eight weeks of interval training and caffeine supplementation on glycemic indices in men with type 2 diabetes.

The current research was a semi-experimental study. As a pilot research, 50 people were selected trough an available and targeted manner, among men with type 2 diabetes (with a history of more than one year) referring to Salamat and Sheikh Al-Rais Specialist clinics, Tabriz, Iran In the period of 2020-2021. 32 people met the inclusion criteria and entered into the study. Participants in the study were simple randomly divided into four homogenous groups of 8 including; Placebo, caffeine, exercise and exercise + caffeine were divided. Drug interventions and intermittent exercises were performed for 8 weeks. Blood samples were collected during two stages (pre-test and post-test) to measure serum levels of glucose, insulin, HbA1c and HOMA-IR index. The data were analyzed using repeated analysis of variance, Bonferroni post hoc and independent t tests at a significance level of 0.05.

The results showed that the levels of the glucose, insulin, HbA1c, and HOMA-IR in the three intervention groups significantly decreased compared to those in the placebo group (P=0.001). Furthermore, the results of post hoc test showed that the combined group of interval training + caffeine, compared to the caffeine group, had double effects on the changes in studied indices (P=0.001).

A combination of interval training and caffeine supplementation may have been adopted as an effective method to improve and treat symptoms associated with type 2 diabetes.

In obesity, the serum levels of Asprosin are pathologically upregulated, this is thus considered a therapeutic target. This study aimed to explore the effect of exercise training as combined training (Aerobic+ Resistance training) along with Caffeine supplementation on the plasma levels of Asprosin in middle-aged obese men. 38 obese men aged 35 to 50 years, with a BMI of greater than 28 participated in the research. They were stratified randomized into 4 groups. including: 1-Control-placebo (n=10), 2- Caffeine (n=10), 3- Combined training-placebo (n=9) and 4- Caffeine and combined training (n=9). The caffeine group consumed the caffeine tab 4.5 mg per kg body weight, daily, for 6 weeks. The Combined training group had concurrent aerobic and resistance training for 6 weeks (3 sessions per week). Blood samples were collected before and after the intervention, and the plasma asprosin concentration was measured by the ELISA method. By the effect of the Combined training, the Asprosin level was reduced (p=0/01). Taking Caffeine alone did not significantly reduce Asprosin (p=0/19). The Asprosin declined in the group that had both Combined training and Caffeine (p=0/01). In order to reduce the upregulated Asprosin in obese individuals known as pathologic, combined training is recommended and/so it is not necessary to take caffeine along with the training.

The present study was conducted to compare the effects of caffeine and doxapram on respiratory and hemodynamic parameters of patients admitted to the intensive care unit after spine surgery.

The current study is a randomized clinical trial that was performed on patients who are candidates for spine surgery at Al-Zahra Hospital in Isfahan. 90 patients who were candidates for spine surgery were divided into three groups of 30 with doxapram, caffeine, and placebo using the block randomization method (with 9 blocks). Hemodynamic variables, number of apneas, duration of apnea, and the time interval between recurrence of apnea were monitored and recorded every 6 hours to 48 hours after surgery.

The mean percentage of oxygen saturation, diastolic blood pressure, and heart rate did not show a significant difference between the three groups. However, systolic blood pressure was significantly higher in the control group. The mean number of apneas in patients and also the mean duration of apnea in the doxapram group were lower. In this regard, the time interval between the recurrence of apnea in the doxapram group was more than the other two treatment groups.

Doxapram had a stronger effect than caffeine in reducing the parameters of apnea duration and its number; it was also able to improve the time interval between them.

Caffeine, a natural substance found in coffee and tea, can have anticancer effects by reducing cell proliferation and inducing apoptosis. On the other hand, nanocarriers can be used as a suitable method for properly delivering drugs at the tumor site, protecting drugs, targeting specific organs, and high durability. This study aimed to produce caffeine nanoemulsions and evaluate its anticancer effects on leukemia cells.

In this experimental study after producing caffeine nanoemulsion and evaluating its physicochemical properties, K562 cancer cells were treated with different concentrations of these caffeine nanoemulsions and free caffeine, and then, the viability of cancer cells was determined using Neutral Red and Trypan Blue methods. The AO/PI test was also used to evaluate the rate of apoptosis and necrosis. Data were analyzed by one-way ANOVA and Tukey's test using SPSS v.16 software.

The results showed that the decrease in the viability of cells treated with different concentrations of caffeine nanoemulsion and free caffeine was both concentration- and time-dependent, and caffeine nanoemulsion has more cytotoxic effects on cancer cells than free caffeine. The results also showed that caffeine nanoemulsion caused more apoptosis-type cell death in treated cancer cells.

The present study indicated a decrease in the viability and induction of apoptosis in K562 cells as a chronic myeloid leukemia cancer cell line after exposure to caffeine nanoemulsion, and caffeine nanoemulsion can be suggested as an adjuvant therapy along with other treatments for the treatment of chronic myeloid leukemia cancer.

The enzymatic defense system includes the enzymes glutathione peroxidase, catalase, and superoxide dismutase, which are responsible for intracellular protection [1]. One of the most important products of lipid peroxidation is malondialdehyde, which has been of great interest and is considered the main indicator of oxidative stress [4, 5]. Aerobic and endurance exercises can improve tissue resistance against harmful stimuli that improve intracellular oxidative stress and apoptosis [7, 8]. Following intense physical activities, with an increase in reactive oxygen species and lipid peroxidation, including malondialdehyde, and an imbalance between oxidative stress and antioxidant defense, a decrease in total antioxidant capacity occurs [11]. Caffeine increases heart protection by negatively regulating inflammatory and apoptotic pathways in rats [13]. Songstad et al. showed that performing six weeks of intense interval training caused no significant difference in the amount of total antioxidant capacity and malondialdehyde in the liver and heart tissue of pregnant rats [12]. According to the conflicting results of the research regarding the effect of intense intermittent exercise on cardiac oxidative stress indicators and/or the use of caffeine supplements on oxidative stress indicators, it is necessary to conduct a study in order to find an effective non-pharmacological solution to reduce these indicators on the heart of rats. Therefore, the present research was done to investigate the effect of eight weeks of intense intermittent exercise and caffeine supplementation on the levels of malondialdehyde and the activity of superoxide dismutase and catalase enzymes in the heart tissue of male rats.

Methods :

In this experimental study, 40 male Wistar rats with an average age of 8 weeks and an average weight of 200-220 grams were purchased from the Center for Research and Breeding of Laboratory Animals at Pasteur Institute, Tehran. After two weeks of familiarization with the environment and how to perform the activity, the rats after weight matching were randomly divided into four groups (n=8) including 1- healthy control (C), 2- exercise, 3- caffeine supplement, and 4- caffeine supplement. The training program included running on a treadmill in two-minute intervals for eight weeks and every week for five days. The warm-up and cool-down phase at the beginning and end of the main phase of the exercise was performed with an intensity of 40-50% of the maximum speed (16-20 m/min) for 5 minutes on the treadmill. Animals performed high-intensity interval training (5 to 12 2-minute bursts with an intensity of 90-85% of the maximum running speed and a minute of rest between bursts and 10 meters per minute equivalent to 30-40% intensity of the maximum oxygen consumption) at 19-20 pm, on a treadmill [9]. The control groups did not participate in any activity program. Then, 48 hours after the last training session. a part of the left ventricular tissue of the heart was carefully removed and frozen in nitrogen at -80°C. Pure anhydrous caffeine powder (dry) prepared from Merck, German was administrated according to the body weight of the animals (70 mg per kilogram of body weight) by intraperitoneal injection from 15:00 to 17:00 for eight weeks and five days per week [14]. Each 100 mg of tissue was homogenized in 1 ml of saline phosphate buffer containing antiprotease cocktail by a homogenizer, and then the tissue was homogenized in Rcf 10,000 for 15 minutes at 4 °C and the supernatant was collected and used to measure the biochemical indices of the research. 

Statistical Analysis:

The Kolmogorov-Smirnov test was used to check the normal distribution of the data. To investigate the difference between groups, a one-way analysis of variance and Tukey's post hoc test were performed at a significance level of less than 0.05 using SPSS software.

The results of the one-way analysis of variance showed a significant difference in the levels of malondialdehyde (P<0.001 and F=508.808) and the activity of superoxide dismutase (P<0.001 and F=115.266) and catalase (P<0.05) between groups. The results of Tukey's test showed that the level of malondialdehyde in the caffeine group (P=0.081) did not change significantly compared to the control group, but it decreased significantly in the training group (P=0.01). Following high-intensity interval training and caffeine consumption, the level of malondialdehyde decreased significantly (P=0.0078) compared to the control group, although the decrease in malondialdehyde levels in the caffeine+training group was not significant compared to the caffeine and training groups (P=0.07). The levels of superoxide dismutase in the caffeine (P=0.02), training (P=0.012), and training+caffeine (P=0.0083) groups had a significant increase compared to the control group and the simultaneous effect of exercise and caffeine was not significant compared to the caffeine and training groups (P=0.14). Also, catalase levels increased significantly in the research groups compared to the control group (P=0.019 in the caffeine group, P=0.001 in the training group, and P=0.0094 in the training+caffeine group).

Discussion :

In this study, there was a significant decrease in the levels of the oxidative index, malondialdehyde, and a significant increase in the activity of the antioxidant enzymes superoxide dismutase and catalase in the heart tissue of the caffeine+training group in comparison with the healthy control group. In the present study, an increase in the levels of superoxide dismutase was observed following caffeine consumption, which was associated with a decrease in the levels of malondialdehyde. This result is inconsistent with the findings of Ashrafi et al. [16] and Saker et al. [15], possibly due to the amount of caffeine consumed. In line with the results of this research, Bafghi et al. showed that eight weeks of interval training in 3-minute intervals with an intensity of 80% oxygen consumption and for 20 minutes in each session, along with curcumin supplementation, significantly increased the activity levels of superoxide dismutase and catalase enzymes [22].

Athletes use variety of compounds to improve athletic performance and are constantly striving to improve capacity and performance. Various supplements are used by the masses and regularly by athletes in exercise to take advantage of the energizing properties as well as to prevent or delay fatigue (1). Dietary supplements, in addition to proper exercise and nutrition to improve athletic performance, are recognized, including caffeine and nitrate supplements. Since both beet juice and caffeine supplements are safe, effective, and legal, it seems that combining these two supplements and using them by athletes can have an increasing effect on improving athletic performance. Caffeine is used by many athletes as an ergogenic supplement, and low and moderate doses of caffeine (3 to 6 mg/kg) are very useful for a variety of exercise (2).
Also, the use of beet juice supplementation in speed runners increased the concentration of lactate in the blood, while there was no difference in the amount of oxygen consumed (7). According to the results of other studies, it seems that the use of nitrate supplementation can reduce the time required to run 10 km and maintain lactate levels in the constant range. However, it seems that 30 days of nitrate supplementation combined with continuous aerobic exercise can improve the performance of running 10 km compared to running alone, one of the mechanisms for which is stability at the surface Blood lactate (8). The results of a study showed that the use of nitric oxide as supplement can accelerate the clearance of lactate from the body after exercise and thus accelerate recovery (9).  In study of Bescós et al. (2011) two randomized blinds stated that the use of nitrate supplementation as a single dose of 10 mg per kg of body weight 3 hours before exercise had an effect on athletic performance and arrival time. Also, it did not cause fatigue and the use of this supplement and with this dose did not affect the heart rate (10). Belbis et al. (2018) examined the effect of 200 mg of caffeine on repetitive running activity on heart rate and lactate levels. The results of this study showed that caffeine supplementation at dose of 200 mg can increase performance in repetitive doses compared to counterparts in the control group (11).
Due to the very limited studies of supplementation of caffeine and beet juice and the lack of comparison of doses used in professional runners with field protocol and considering the conditions of intense aerobic and anaerobic training subsequently and in a short time in most sports to Improves anaerobic power and lactate threshold, as well as strengthens cardiovascular endurance during training and tournaments that probably have more than one training session per day, and considering that running is used as one of the pillars of training to increase the performance of athletes by coaches., Therefore, the aim of this study was to investigate the effect of short-term caffeine-beet juice supplementation on catecholamine changes, lactate and Rating of Perceived Exertion following intense anaerobic activity in elite male runners.

In this quasi-experimental study, 30 elite male runners (age 27.5±3.8 y, height: 176.7±7 cm, body fat: 9.9±1.7 %) were randomly divided into three exercise groups with 1) high dose supplement (9.6 mmol Beet extract and 400 mg caffeine), 2) low-dose supplement (4.8 mmol beet extract and 200 mg caffeine) and 3) placebo group (natural beet juice). total of 36 sessions were performed in three stages and two stages of six-day wash out between the first and second stages and the second and third stages. Levels of epinephrine and norepinephrine, lactate and pressure perception were measured. Data were analyzed using analysis of variance with repeated measures at the P<0.05.

The results showed that supplementation and exercise no significant changes in epinephrine levels (p = 0.93), norepinephrine (p = 0.89) and lactate (p = 0.37), but has had a significant effect on the perception of runner pressure (p<0.001). Also, supplementation and exercise caused significant changes in catecholamine levels (p<0.001). As the time elapsed after running, lactate levels decreased more than at baseline (p<0.001). Also, with increasing running distance, the rate of pressure perception increased (p<0.001).

The results of the present study showed that short-term supplementation with beet juice and caffeine was not able to significantly change the levels of catecholamines, lactate in elite runners, but was significantly reduce the pressure perception. The findings of this study were consistent with the results of Previous research (14-19). It has been shown that nitrate supplements for 15 days can reduce the perception of pressure, increase oxygen saturation and also increase the time to reach fatigue (23). Nitrate is an organic ion found in many foods, especially vegetables such as celery, beets, lettuce and spinach (24, 25). Following consumption, nitrate enters the bloodstream and has a shelf life of about 5 hours. Once absorbed into the bloodstream, nitrate is converted to nitrite and then nitric oxide, which can dilate blood vessels, increase blood flow, reduce muscle energy expenditure, improve nutrient delivery to muscle, and increase calcium ion release, and ultimately Improve runners' performance (26,27). Short-term nitrate supplementation appears to increase nitric oxide bioavailability and inhibit sympathetic vasoconstriction in resting or contracting muscle, however, some studies have shown conflicting results. Nitrate supplementation has been shown to be unable to alter vascular contraction due to sympathetic effects in young male athletes (27). also, the physiological effects of caffeine supplementation are not well understood, but it appears that the effects of caffeine on heart rate are influenced by the intensity of exercise and caffeine supplementation can reduce heart rate and blood pressure perception (32). It seems that the lack of significance in high and low doses of caffeine and beet juice supplementation on catecholamine variables indicates the lack of sympathetic effect of this combined supplement or that the presence of caffeine and nitrate together can neutralize each other. In relation to the exercise pressure perception index, the difference in the dose received by this combined supplement had a significant effect, which indicates that by increasing the amount, the pain perception threshold can be increased. Possible mechanisms include vasodilation, increased blood flow, improved delivery of nutrients and oxygen to the muscle, and increased calcium ion release and reduced fatigue. One of the limitations of this study is the lack of precise control of subjects in terms of food intake between the second to seventh day and also in the rest period between each stage. It also seems that individual differences in athletes' eating habits and body reactions may affect the response to variables due to the short duration of the intervention, especially in the case of caffeine, which despite the relative control during the study but the body Athletes show different responses to it, or the duration of the research is limited due to the professionalism of the athletes and the time that coaches allow them to participate in applied research. One of the strengths of this research is the use of supplements that are extracted from natural and daily foods. It is suggested that in future research on the recommended amounts of supplements with several different doses or in combination with other ergogenic supplements, preferably with a nutritional nature and not chemical and with a synergistic effect similar to this study and with longer use or in non-professionals. As well as other sports with the nature of endurance, strength or speed and skill to be considered. The results of this study showed that short-term supplementation with caffeine and beetroot juice as a source of nitrate did not cause significant changes in catecholamine, lactate and heart rate, but caused significant changes in runners' perception of pressure. Further studies are also needed to investigate possible mechanisms involved in athletes' anaerobic performance and more effective doses. It does not seem to combine these two supplements with each other or in higher doses compared to smaller amounts.

 The immune system is affected by a variety of physiological and psychological pressures (1). Exercise has been shown to impair immune system function, which appears to depend on the intensity and duration of exercise and the secretion of stress hormones (2). Exercise in a high temperature environment has a synergistic effect on stress responses to exercise (3, 4). Acute stress (e.g., cortisol) and inflammatory responses (e.g., cytokines) after exercise at warm temperatures are greater than those seen at lower temperature conditions (5). Heat stress caused by high ambient temperatures can affect physical function; Tolerance to exercise in hot environments is lower than cold environments (6). There have been numerous reports of increased plasma cortisol responses (9, 10) and production of cytokines (4, 11) seeking to limit fluid intake during acute exercise. Recently, Costello et al. (2018) showed that acute exercise in a warm environment increases the levels of interleukin-6 (IL6) and plasma cortisol only in conditions of fluid restriction (12). Ignoring the increase in physical and psychological stress experienced while exercising in conditions of ambient heat and dehydration combined with improper recycling can increase the risk of various diseases (4, 13) and impair athletic performance (14). Caffeine is one of the most common dietary supplements in the world, which has been used as a factor to increase physical-mental functions and delay fatigue in athletes (15). Also, caffeine, with its energizing and anti-inflammatory properties, in addition to increasing athletic performance, can reduce the inflammatory responses caused by strenuous exercise (16, 17). In this regard, Fedor (2010) examined the acute use of two doses of 4 and 7 mg / kg body weight of caffeine and showed that only higher doses of caffeine can prevent proinflammatory cytokines caused by moderate-intensity endurance training (18). Jafari et al. (2014) showed that acute consumption of 6 and 9 mg / kg body weight of caffeine inhibits the increased response of serum tumor necrosis factor (TNFα) following a period of debilitating resistance activity (19). However, the lack of effect of acute caffeine consumption on the response to inflammatory markers following exercise has also been reported in some studies (20, 21).
consumption to possibly modulate the response to inflammatory parameters caused by exercise in conditions of ambient heat and dehydration has not been studied. Research findings also indicate a discrepancy between the results regarding acute caffeine consumption and the response to inflammatory markers following exercise; Considering the important role of caffeine supplementation along with exercise on physical function as well as reducing inflammation, it seems that the study of the effects of exercise and caffeine supplementation on inflammatory markers is of great importance, but according to studies, the findings are very limited in this regard. Therefore, the aim of this study was to investigate the effect of caffeine supplementation and exhausting exercise on inflammatory factors in hot environments.

In this experimental study, 30 male athletes with an average age of 26.6 ± 3.9 years in dehydrated conditions were selected in an accessible and targeted manner and divided into three groups of caffeine consumption (number = 10 people), placebo group (number = 10 people) and the control group (number = 10 people) were divided. Caffeine group consumed 6 mg / kg body weight of caffeine. 60 minutes later, the subjects performed a series of increasingly exhausting aerobic exercise. Data were analyzed using analysis of variance with repeated measures, One-way ANOVA and Tukey post hoc test at the P<0.05.

The results showed that immediately after exercise, the levels of IL1B, TNFα and IL6 were significantly higher than the control group (p≥0.001). The caffeine group experienced a greater increase in IL6 (p≥0.001) and IL1B (p≥0.05) and a smaller increase in TNFα compared to the sham group (p≥0.001). Also, hs-CRP levels were significantly higher than baseline in the exercise group (p≥0.001).

The results of this study indicate that maximal aerobic function increased following caffeine consumption. The findings of this study were consistent with the results of Previous research (26-28). In this study, we used the Bruce treadmill test, while in the study, the 20-meter shuttle test was used as the maximum aerobic test. In addition, the high ambient temperature and dehydration conditions present in the present study could be another reason for the differences in the present results with the study of Lamina and Musa (29). The results showed that acute exercise significantly increased plasma IL1β, IL6, TNFα and hs-CRP levels in caffeine and sham groups. Consistent with these findings, increased blood levels of inflammatory agents following acute exercise have been reported in many studies (27, 30). Consistent with the results of the present study, previous studies have shown that caffeine consumption increased the IL6 response after maximal aerobic activity (34, 35). One of the reasons for this observation is that more cytokine secretion through caffeine consumption is associated with higher power output and greater metabolic stress (further increase in adrenaline and plasma lactate after exercise) (34, 35). Therefore, it seems that caffeine consumption may not have a direct effect on IL6, but rather increases the IL-6 response by increasing potency and consequently the need for higher metabolism.

One of the important findings of the present study was that acute caffeine consumption did not affect basal inflammatory factors, because there was no difference between the mean levels of basal inflammatory factors in the study groups. This observation is consistent with the results of studies by Arsenault et al. (36) and Kempf et al. (37), but with the results of studies by Fletcher and Bishop (38) and Jafari et al. (19) that increase basal levels of inflammatory markers in response to Acute caffeine consumption has been reported to be inconsistent. One possible reason for this discrepancy may be related to the conditions of the subjects; The subjects in the present study were in dehydrated conditions and at ambient temperature, which may have increased the basal levels of inflammatory markers by increasing the secretion of stress hormones and, therefore, reduced the effect of caffeine on these factors. Because the secretion of stress hormones (epinephrine and cortisol) has been cited as one of the basic mechanisms for increasing basal levels of inflammatory markers due to caffeine consumption (38, 39).
 In the present study, acute caffeine consumption further increased plasma IL6 levels in response to exercise. Consistent with this finding, some previous studies in this field have reported higher increases in plasma IL6 levels following exercise in subjects who consumed caffeine (35, 40). This higher increase in IL6 levels following caffeine supplementation is mainly attributed to a decrease in IL6 clearance by the liver, which occurs due to decreased visceral blood flow due to increased adrenaline (30). Another finding of the present study was that acute caffeine consumption reduced the rate of exercise-induced increase in TNFα. Horrigan et al. (2004) showed that caffeine consumption suppresses the production of proinflammatory cytokine TNFα in human blood and this effect is mediated by modulating the cyclic AMP / protein kinase A signaling pathway (41). Caffeine and its metabolite, theophylline, have also been shown to directly activate the enzyme histodoniestylase, which also distills central histone and reduces the transcription of inflammatory genes (17). In the present study, elevated IL1β and TNFα levels returned to baseline levels during blood sampling 24 hours after exercise in subjects experiencing caffeine supplementation, but remained elevated in the sham group. There were some limitations in the present study, such as the lack of measurement of other inflammatory factors. Examining the effect of different doses of caffeine supplementation after exercise can also help to better explain and interpret the results. This is a research weakness suggested by future studies to measure these post-exercise indicators along with caffeine consumption in athletes. It seems that the maximal exercise in hot environments and dehydration status increases the release of inflammatory markers that appear to be moderated by caffeine consumption. Also, caffeine use is associated with faster recovery of inflammatory status.

Dietary intakes are one of the factors influencing the incidence of chronic kidney disease. The present study was performed to investigate the possible long-term effects of caffeine, tea and coffee consumption on the incidence of chronic kidney disease.

1780 adults participating in the third phase of the Tehran Lipid and Glucose Study (TLGS) (2006-2008) were selected for inclusion criteria. Dietary intakes were assessed using a food frequency questionnaire (FFQ). Demographic variables, anthropometrics, and biochemical data were measured at baseline and after six years of follow-up. To estimate the risk of chronic kidney disease, logistic regression analysis, adjusted for possible confounding variables, was used.

Participants’ mean (±SD) age at baseline was 33.96±15.40 years. During six years of follow-up, the incidence of chronic kidney disease (CKD) in the population studied was 17.9%. After adjusting confounding variables, the incidence of CKD did not show any significant relationship with tea, coffee, or caffeine intakes (adjusted odds ratio and confidence intervals for CKD in the third tertile of tea and caffeine intake compared to the first tertile and in coffee drinkers compared to non-drinkers were 0.92 (0.68-1.25), 0.87 (0.63-1.21) and 1.17 (0.90-1.51), respectively).

Inverse and non-significant relationship between tea and caffeine consumption with the incidence of CKD and a direct and non-significant relationship between coffee consumption and the incidence of CKD were observed in this study, necessitating further prospective studies to investigate the effects of dietary intakes on CKD.

Caffeine is a purine alkaloid with anti-oxidant and anti-inflammatory effects.This study aims to evaluate the effect of long-term caffeine consumption and aerobic exercise on seruminterleukin-6 (IL-6) level and body composition in obese men.

In this quasi-experimental study, 40 obese men (Mean age=32.8±2.74 years, bodymass index=30.98±1.37 kg/m2) were randomly divided into four Group of 10 including placebo, supplementation,placebo + exercise, and supplementation + exercise. The aerobic exercise program includedrunning for 8 weeks, 3 sessions per week, each for 25-45 minutes with an intensity of 55-85% of themaximum heart rate. The supplementation group received 500 mg caffeine daily and the placebo groupreceived 500 mg capsules of 2% maltodextrin. Blood samples were taken following 12 hours of fastingbefore and 48 hours after the last training session to measure IL-6 level. Data were analyzed using onewayANOVA and Tukey’s post hoc test. The significance level was set 0.05.

In the exercise+supplementation and placebo+exercise groups significant decreases werereported in the serum level of IL-6 compared to the supplementation and placebo groups in thepost-test phase (P<0.05). There was also a significant decrease in body composition of groupsplacebo+exercise, exercise+supplementation, and supplementation compared to placebo group inthe post-test phase (P<0.05).

Aerobic exercise alone and in combination with long-term caffeine consumption can reduceIL-6 level and improve body composition in obese people.

Proper recovery can affect complex balance, psychomotor, and fatigue performance. So, the present study aimed to investigate the effect of cumin intake following partial sleep deprivation (PSD) on the oxidation of carbohydrates and fats and some cardiorespiratory indices in student-athletes.

The study was quasi-experimental with cross-sectional design. The subjects were 18 female student-athletes (Age: 18-25 years), who were recruited voluntarily. Then, they were assigned into immersion in cold water, immersion in cold water, placebo (including dextrose) and immersion in cold water with supplementation. Caffeine and placebo were taken one hour before the test and after one hour, the participants took balance, Bruce and Vienna tests. Repeated analysis of variance and Bonferroni correction test were used at the significance level of 0.05.

Exhaustion time and heart rate in student-athletes improved significantly after immersion in cold water and caffeine consumption (P≤0.05). Also, motor and motor function (reaction speed) improved with caffeine consumption (P≤0.05). On the other hand, the indices related to static and dynamic balance were not significantly different (P≥0.05).

Caffeine supplementation and immersion in cold water affect the indicators of fatigue and psychomotor function in student-athletes following a burn out exercise protocol.

Caffeine can affect many physiological functions of the body. The aim of this study was to investigate the response of aerobic function, blood pressure and some immune system factors of trained men to acute caffeine consumption in dehydrated condition and warm and humid environment.

Thirty male athletes with a mean age of 26.6±3.9 years in dehydrated conditions voluntarily participated in this study, which was performed in a double-blind manner. Subjects were divided into three groups: caffeine consumption group (n=10), placebo group (n=10) and control group (n=10). The Caffeine group consumed 6 mg/kg body weight of caffeine. Sixty minutes later, the subjects performed an increasingly exhausting exercise. Blood samples collecting and blood pressure measuring took place before, immediately after and 24 hours after exercise. Analysis of variance with repeated measures (group * time) and one-way analysis of variance were used for statistical calculations.

The duration of the exhaustion test in the caffeine consumption group was significantly longer than the control (p≤0.01) and placebo (p≤0.05) groups. In the blood sampling immediately after exercise, the level of leukocytes, neutrophils and lymphocytes in the exercise groups were significantly higher than the control group (p≤0.001). Also, the caffeine group experienced a lower increase in leukocytes and neutrophils compared to the placebo group (p≤0.001). Blood pressure values ​​in the exercise groups were significantly higher than the control group (p≤0.001). Also, the caffeine group experienced a greater increase in systolic blood pressure at baseline and immediately after exercise compared to the placebo group (p≤0.001).

In general, exhausting exercise in a warm environment and dehydrated condition increases the number of immune system cells and blood pressure. In addition to improving aerobic function, caffeine seems to prevent further increases in the number of immune system cells, while increasing blood pressure in the normal range in warm and humid environment.

Physical inactivity is associated with low-grade systemic inflammation and increased risk of chronic diseases. Beneficial effects of caffeine on adipocytes metabolism and its anti-inflammatory properties have been reported. This study aimed to evaluate the impact of 12 weeks of combined training and caffeine on plasma levels of inflammatory and anti-inflammatory indices in obese men. 

In a quasi-experimental trial, 44 obese men were purposefully and accessibly selected and assigned into four groups each 11 samples: 1) control, 2) combined (resistance-endurance) training, 3) caffeine, and 4) combined training with caffeine. The study subjects received 6 mg of caffeine per kilogram of body weight daily for 12 weeks. The combined training program was performed for 12 weeks, 3 sessions per week. The plasma levels of inflammatory (interleukin[IL]-1β) and anti-inflammatory (IL-10) indices were measured using an ELISA kit. The obtained data were analyzed by dependent t test, 1-way ANOVA, and Tukey post hoc test at the significant level of P<0.05.

The results showed that 12 weeks of combined training, caffeine, and combined training-caffeine significantly reduced IL-1β levels and increased IL-10 in obese men at posttest compared to the pretest (P=0.001). Also, changes in IL-1β and IL-10 levels were greater in the combined training-caffeine group (P=0.001). 

 Combined training with caffeine positively affects body composition and improves inflammatory and anti-inflammatory indices in obese people.

Overweight and obesity are associated with increased inflammatory conditions and metabolic disorders. A therapeutic agent that can suppress metabolic and immune disorders may effectively ameliorate parallel abnormalities in obesity. The aim of this study was to evaluate the effect of combined training and caffeine supplementation on Toll-like receptor 2 (TLR2), TLR4, and dectin-1 in obese men.

In a semi-experimental trial, 44 obese men were purposefully and accessibly selected and randomly divided into four groups: 1) control, 2) combined training, 3) caffeine and 4) combined training -caffeine. Subjects received 6 mg of caffeine per kilogram of body weight daily for 12 weeks. The combined training program include circular resistance training (3 times with 14 repetitions at 50% of one maximum repetition and 30 seconds rest between each station) and aerobic exercise (70% maximum heart rate for 30 minutes) was performed 3 sessions per week for 12 weeks. The combined training program was performed for 12 weeks and 3 sessions per week. Data were analyzed with covariance analysis and Tukey post hoc test at the p<0.05.

The results showed that 12 weeks of combined training, caffeine and combined training - caffeine significantly reduced serum levels of TLR2, TLR4 and Dectin-1 (P=0.001). The reduce of serum levels of TLR2, TLR4 and Dectin-1 were significant in the combined training compared to caffeine group (P=0.001). the effect of interactive combined training with caffeine was more than supplementation and training alone.

According to the findings, it is suggested that combined training intervention with caffeine consumption be used in order to reduce its inflammatory effects associated with obesity.

Diabetes is a common metabolic disease that leads to impaired hepatic glycogen synthesis. The present study investigates the effect of eight weeks of intense intermittent exercise (HIIT) and caffeine consumption on glycogen synthase (GYS2) expression and liver glycogen levels in diabetic rats.

In an experimental clinical-intervention study, 50 streptozotocin-induced diabetic rats were divided into 5 equal groups of control (C), diabetic (D), supplemental diabetic (D + CAF), diabetic with exercise (D + T), supplement and exercise (D + CAF + T). The training program consisted of eight weeks, 5 sessions per week (6 to 12 2-minute sessions with an intensity of 85-90% of the maximum speed) and 70 mg/kg of caffeine were injected five days a week. After anesthesia, liver tissue was extracted and the expression levels of (GYS2) and liver glycogen were assessed. Data analysis was performed by independent t-test and two-way ANOVA at a significant level of (P<0.05).

Induction of diabetes significantly reduced hepatic glycogen and GYS2 expression (P<0.001). Also, caffeine consumption (P<0.01) and HIIT (P=0.024) both significantly increased GYS2, which had a greater effect of caffeine with a 44% effect size. Also, HIIT (P=0.529) and caffeine (P=0.761) neither alone, nor in combination (P=0.12) caused a significant increase in hepatic glycogen.

According to results, it is possible to suggest HIIT and caffeine consumption as an effective intervention to improve (GYS2) expression. However, a clear statement requires further research in this area.

The use of nanoparticles in biomedical research have been increasingly developed in recent years. One of the applications of nanotechnology is the use of compounds such as hydrogels, micelles, nanoliposomes, nanofibers and niosomes as a delivery system to treat cancer. The aim of this study was to evaluate the ant antitumor effect of the caffeine-loaded niosomes on MCF-7 human breast cancer cell line.

The thin film hydrate on method was used to prepare caffeine-loaded niosomes. Certain amounts of surfactant, caffeine and cholesterol were dissolved in ethanol. Rotary evaporation was used to remove solvent from reaction mixture. Sample was dissolved in the phosphate buffer and homogenized with sonicator. The average diameters of caffeine-loaded niosomes were measured using a Zetasizer Nano system.  Finally, the cytotoxicity effect was evaluated by MTT assay.

The treatment of breast cancer cells with different concentrations of nano-sized drug and free drug showed that the nanoparticles had the ability to inhibit the MCF7 proliferation more than free drug. 0.25 mg/ml of niosomal drug had a greater effect on reducing of cancer cells viability.

Vesicular nanoparticles are complex systems with some advantages and disadvantages which sets these delivery systems apart from other colloid system. Vesicular nanoparticle is being developed as new drug delivery system for cancer treatment.

Imbalanced production of adipokines as leptin and adiponectin in diabetic patients may lead to the development of metabolic complications. Therefore, the aim of this study was to determine the effects of 2-month of caffeine ingestion along with aerobic training on changes in serum leptin and adiponectin levels and leptin/adiponectin ratio (LAR) in type 2 diabetic men.

Thirty-two diabetic men participated in a quasi-experimental designs in the four groups for two-months period of a aerobic training (treadmill walking 3 times/week, 1.5 hour/session, 65-85% HRR) with and without caffeine ingestion (3 mg.kg-1.day). Serum changes in leptin and adiponectin were measured during two phases (baseline and 24-hours after completing of the training program). Data were analyzed by one-way ANOVA and bonferroni's post-hoc test at level P≤0.05.

Administration of two-months caffeine (CA) alone and combination with aerobic training (AT) were significantly could reduced and increased in leptin and adiponectin level, respectively (P=0.001). Thus, the combined group (AT+CA) effect were far more appropriate intervention in changing the studied indices (P=0.001). Also, the LAR method was notable reduced in all study groups, although these effects were more significantly in the combined group (AT+CA) (P=0.001).

It seems administration of caffeine supplementation and aerobic training for two-months have a positive effects on the improved relative of leptin and adiponectin levels as well as their ratio in diabetics, although the combination of these two variables has been shown to have far more dual effects.