Effect of Caffeine on Obesity and Its Application in the Treatment of

Obesity

Xinlu Yun

Institute of food, Shenyang Agricultural University, Shenyang, Liaoning, China

Keywords: Caffeine, Obesity, Ephedrine, EGCG, Appetite.

Abstract: Obesity is a chronic metabolic disease, it is not only listed in the top ten chronic diseases by WHO, but also

is a risk factor in many other chronic diseases. At present, the treatment of obesity mainly includes lifestyle

intervention, drug therapy and surgery. Drug therapy was initially popular as a way to lose weight quickly

and has little trauma, but people gradually lost faith in it due to its endless negative news. Therefore it is

important to seek a natural substance with very low side effects as a source of drugs for obesity treatment.

Caffeine is a natural substance that is ubiquitous found in people's lives, making it more acceptable as a

treatment for obesity. Therefore, this paper aims to study the influence of caffeine on obesity, the

application of caffeine in the treatment of obesity and the prospect of caffeine as a weight loss drug,

expecting to provide new ideas for the development of natural weight loss drugs. Finally, through literature

analysis and case studies, it is concluded that caffeine can play a positive role in the treatment of obesity by

suppressing appetite and accelerating lipid metabolism, and that the combined use of caffeine with EGCG

or ephedrine has a more significant effect than caffeine alone.

1 INTRODUCTION

Due to the development and progress of the Times, a

large number of delicious foods, especially the

mixture of sugar and oil, appear in people's life.

Meanwhile, due to the progress of science and

technology, people have less opportunity to put their

physical strength into some sports or activities,

resulting in the increase of obesity. Obesity is a

chronic metabolic disease, it will not only take a toll

on health, such as increasing the rate of

cardiovascular disease, type 2 diabetes, osteoarthritis

and other diseases, but also it will has a great impact

on life, and even produce the psychological problems

such as depression. Thus, the prevention and

treatment of obesity has become today's global hot

spots (Seidell 2015). At present, the main treatment

methods of obesity include lifestyle intervention,

drug therapy and surgery. Among them, most of the

studies are related to drug therapy, such as lillutide,

which can suppress appetite, orlistat and inhibit

lipase activity in gastrointestinal tract. However,

there are also many drugs that have been phased out

due to the side effects. Therefore, weight-loss drugs

with "natural ingredients and low side effects" have

also become the focus of research in recent years.

Coffeeand tea have always been considered by many

people to have the effect of weight loss, but most of

the relevant studies on caffeine are about its main

ingredient or about its effects on apnea or

neurodevelopment treatment of premature infants,

and there are few relevant studies in whether it has an

impact on obesity treatment and the mechanism of

obesity. Thus, this paper will discuss how obesity is

produced, whether caffeine has an effect on obesity,

the specific application of caffeine in the treatment of

obesity and whether it can be widely used as a drug

in the treatment of obesity, expecting to provide a

safe and effective new idea for obesity treatment and

bring help to the obese people.

2 CAFFEINE AND OBESITY

In recent years, refreshing drinks such as coffee and

tea have become popular among young people and

those who need to stay up late at work. Caffeine has

also entered the public's field of vision. However,

Chinese and foreign scholars have different views on

whether caffeine has an effect on weight loss. On the

one hand, some people think that caffeine can

suppress appetite and improve metabolism so as to

450

Yun, X.

Effect of Caffeine on Obesity and Its Application in the Treatment of Obesity.

DOI: 10.5220/0011372000003438

In Proceedings of the 1st International Conference on Health Big Data and Intelligent Healthcare (ICHIH 2022), pages 450-455

ISBN: 978-989-758-596-8

play a role in weight loss, for example, Liu Hanyang

(LIU 2016) and Litong Liu (Liu 2018) believe that

caffeine can boost lipid metabolism or suppress

appetite. On the other hand, some people think that

the effect of caffeine on weight loss is not

obvious,for example, in the study of Schubert

(Schubert 2014) et al, the effects of coffee intake

(caffeinated and decaffeinated) on appetite

perception and energy intake were investigated and

no significant differences were found between the

two groups. So in this section whether caffeine could

alleviate obesity will be discussed.

2.1 The Emergence of Obesity

Obesity refers to overweight and obesity caused by

the accumulation of excessive fat in the body. The

pathogenesis of obesity is also very complex. In

addition to physiological factors, there are also

genetic and environmental factors, but the main

causes of obesity are excessive energy intake and

metabolic disorders.

Among those factors, energy intake is related to

food intake, and food intake is closely related to

appetite. Hunger signals due to insufficient energy

intake and proximity to delicious food can stimulate

appetite and promote eating behavior. And when the

body ingests too much, it will also cause the disorder

of ingestion control mechanism. For example, the

hypothalamus which regulates appetite and energy

balance is composed of multiple nuclei: arcuate

nucleus (ARC), paraventricular nucleus (PVN),

lateral hypothalamic area (LHA), ventromedial

nucleus (VMN)and dorsomedial nucleus (DMN).

The arcuate nucleus (ARC) located in the central

uplift of the hypothalamus, it is considered to be the

main region for sensing peripheral metabolic signals.

In ARC, two distinct but interrelated groups of

neurons are included, one stimulates appetite,

including agouti-related (AgR) released by

agouti-related peptide (AgRP)neurons and

neuropeptide Y (NPY), and the other one suppresses

appetite, including proopiomelanocortin (POMC)

and cocaine and amphetamine regulated transcript

(CART). In addition, some appetite regulation

factors such as appetite stimulating ghrelin and

appetite suppressing leptin, are also produced by the

nucleus of hypothalamus (Zhu 2013).

However, when energy intake is too high, AgRP

level can be increassed by reducing POMC and α

-melanocyte hormone (α-MSH) expression, thus

causing disturbance of feeding control mechanism

and energy imbalance, resulting in increased appetite

and further fat deposition (Zhu 2013).

Obesity is mostly caused by adipose tissue, it is

associated with energy metabolism, brown adipose

tissue (BAT) is used to produce heat and white

adiposetissue (WAT) is used to store fat, obese

patients have more WAT and less BAT but because

of the less amount of BAT group, leading to heat

production, which regulates metabolism, to break

down, causing excess energy to be converted to fat

(Liu 2003), It is also one of the causes of obesity.

However, from the perspective of genetics,

obesity can also be the result of a combination of

genetic and environmental factors. Obesity caused

by heredity is divided into single-gene obesity and

multi-gene obesity. The pathogenesis of single-gene

obesity is mostly caused by abnormal

LEP-melanocortin signaling pathway, which is

manifested as hyperfeeding and early onset of

obesity. While polygenic obesity is generally caused

by DNA variation produced by multiple genes,

which are significantly associated with BMI,waist

circumference, hip circumference and weight (Yu

2020).

To sum up, the causes of obesity are diverse and

are not the results of the action of any single factor,

so obesity treatment should also be "appropriate to

the case".

2.2 Influence of Caffeine on Obesity

Caffeine is a natural methyl xanthine, its chemical

name is 1, 3, 7-trimethylxanthine. Caffeine can be

found in many plants, such as coffee beans and tea.

Caffeine can stimulate the central nervous system,

usually dispel fatigue and refresh the brain, and is

often used in clinical treatment of neurasthenia and

coma resuscitation (Zhang 2021). So it is a popular

central nervous stimulant and widely used in food,

medicine and other fields. In addition, caffeine also

has a certain effect on obesity.

2.2.1 Caffeine’s Effect on Lipid Metabolism.

Caffeine can inhibit phosphodiesterase activity and

increase cyclic amp depends on protein kinase, and

it can induced the downstream of the sympathetic

nervous system and hormone sensitive lipase

reconciliation coupling protein increases, eventually

leading to the increase of energy consumption and

fat oxidation (LIU 2016). Because of caffeine’s

positive impact on the role of fat oxidation, it can

enhance the BAT heat production performance,

prevent the accumulation of body fat, and play a

positive role in the prevention and treatment of

obesity.

Effect of Caffeine on Obesity and Its Application in the Treatment of Obesity

451

2.2.2 Caffeine 's Effect on SNS(sympathetic

nervous system)

Caffeine can enhance the excitability of sympathetic

nervous system (SNS), and SNS plays an important

role in adjusting energy consumption and fat

metabolism. Norepinephrine (NE) is an important

mediator in determining SNS activity, so substance

that can stimulate or prolong the presence of NE can

increase energy expenditure and promote lipid

metabolism. Caffeine can affect activity by

inhibiting phosphodiesterase activity, an enayme

that can rapidly degrade adenosine

monophosphatidylate (cAMP)in cells and is also a

signal of reaction to NE (Yang 2019). Besides,

neuropharmacological studies have proved that

cateholamine like NE, dopamine (DA) and

serotonin(5-HT) neurotransmitter changes can

change feeding behavior, affect appetite, so the

excitement of SNS will have a negative effect on

appetite, thus reducing food intake, and because

appetite and obesity were positively related, the

reduction of appetite will have a positive impact on

obesity treatment (Wu 2000).

But the effect of caffeine on obesity depends on

the amount of caffeine used, individual differences

(age, sex, pregnancy or not), half-life (since caffeine

has a shorter half-life, the loner the time passes, the

less significant the effect), and whether it is used in

combination with other substances.

3 CAFFEINE IN THE

TREATMENT OF OBESITY

While many studies have shown that caffeine does

suppress appetite and improve metabolism, some

studies have shown that caffeine has no significant

effect on energy intake or appetite. So given that, it

would be more likely for caffeine to work in

combination with other substances.

3.1 Synergistic Application of EGCG

and Caffeine

Epigallocatechin gallate (EGCG) is the main

component of green tea polyphenols. Like caffeine,

EGCG is also known for its anti-obesity effects. It

also regulates fat metabolism of obese patients, and

can stimulate the body to produce heat to accelerate

metabolism and reduce the body's absorption of

calories from food.

When EGCG is used alone, the possible

mechanism of its effect on obesity is that EGCG

affects the excitability of SNS, increases energy

consumption, and promotes fat oxidation, which in

turn drives other mechanisms including changing

appetite, up-regulating enzyme activity of liver lipid

metabolism, and reducing nutrient absorption. It can

be seen from the above that the activity of SNS

depends on NE, and EGCG can inhibit the activity

of catechol-o-methyl transferase (COMT), which

candegrade NE, thus prolonging the survival time of

NE. However, due to the low bioavailability of

EGCG (< 1%) and the serious side effects associated

with high doses of EGCG alone, EGCG in

combination with caffeine is a good choice. The

combination of EGCG and caffeine can solve the

problem that each of them can not be used alone

with large doses, and the worry that toxicity may be

produced(because they are from the same

substance). In addition, one of the reasons for the

limited effectiveness of EGCG is also due to the low

bioavailability of it, but effective experiments have

shown that EGCG with different proportions of

caffeine can improve the bioavailability of EGCG.

In the study of Yang Z (Yang 2019), all rats were

treated according to the experimental design in

Table 1: ND group rats had unchanged diet and were

given distilled water intragastrically. The other rats

were fed high-fat diet, and then randomly divided

into five subgroups: obesity group (OB), fed with

distilled water. Low EGCG group (LE), gavage

40mg/kgEGCG. High EGCG group (HE),

160mg/kgEGCG. Caffeine group (CF), 20mg/kg

caffeine intragastric administration. Low dose

EGCG+caffeine group (LE+CF), 40mg/kgEGCG

and 20mg/kg caffeine intragastric administration.

All the experiments were conducted in the morning,

and the volume of intragastic administration was

2ml for four consecutive weeks, and the results were

finally obtained as shown in Figure 1. OB group had

significant difference in weight gain over 4 weeks

compared with ND group. The weight gain of LE

group (57.1±8.9g) and CF group (46.2±7.6g) was

significantly slower than OB group (75.2±10.6g).

But in the HE group (20.3±7.3g) and the LE+CF

group (25.4±6.3g),the weight gain retardation effect

was more obvious, even lower than the ND group

(28.6±4.5g). Therefore, the HE group and LE+CF

group achieved the purpose of weight loss, and the

effect was better than the LE group and CF group.

However, due to the harm of high dose EGCG, it is

not suitable for the treatment of obesity, so the

combination of caffeine and low dose EGCG can be

a good choice for the treatment of obesity.

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452

Table.1: Experimental design and process Quote.

Group name

Group name full name Feed Treatment dose

LE+CF

Normal diet group

Obesity model group

Low EGCG group

High EGCG group

Caffeine group

Low EGCG+Caffeine group

Ordinary feed

High fat feed

Distilled water

40mg/kg EGCG

160mg/kg EGCG

20mg/kg Caffeine

40mg/kg EGCG+20mg/kg Caffeine

Figure1: Weight trend of rats

About how to mix EGCG with caffeine to get the

best results, Litong Liu (Liu 2018) etal discussed the

effects of the combined use of EGCG and caffeine

on anorexia and fat accumulation in mic in their

study, and 15 different concentrations of EGCG and

caffeine were used for 8-week experimental study in

mice, and the optimal ratio and mechanism of

EGCG and caffeine were finally determined. The

inhibitory effect of 0.1%EGCG+0.1% caffeine on

food intake was the strongest, and the decrease of fat

accumulation and body weight was the largest.

In these studies, it was found that the

combination of caffeine and EGCG had a more

significant effect on obesity and was more helpful in

inhibiting weight gain and fat accumulation than

using caffeine alone.

3.2 Synergistic Application of

Ephedrine and Caffeine

Because caffeine stimulates the sympathetic nerve

and thus plays a role in weight loss, it was wondered

whether the combination of ephedrine, which also

has a central stimulant effect, would make the

inhibition of obesity even more significant.

Ephedrine is a kind of epinephrine-like drug, and its

therapeutic effect is better than epinephrine. It is

often used in the treatment of bronchial diseases, etc.

For the combined use of ephedrine and caffeine in

the treatment of obesity, such auxiliary drugs have

been approved to use in foreign countries.

Ephedrine has a similar effect on obesity as

EGCG and caffeine, stimulating fat oxidation,

increasing energy expenditure and suppressing

appetite. Experimental studies indicate that

ephedrine can promote the release of catecholamine

(CA) transmitters, adrenergic receptors, and

promotethermogenesis. However, ephedrine is

affected by thenegative feedback regulation of

adenosine-prostaglandin and cAMP

phosphodiesterase system, they can reduces the

thermogenesis effect, but methyl yellow purine

compounds can affect the system again, so when the

caffeine and methamphetamine collaborative

application can enhance the effect of ephedrine,

Caffeine also contributes to weight loss by

antagonizing adenosine receptors and promoting fat

breakdown and thermogenesis (Wu 2000).

In the study of Greenway et al (Greenway 2008),

a case study was conducted on 3 patients with

hypothalamic obesity who continuously taking

caffeine plus ephedrine hydrochloride. The average

weight loss of these 3 patients was 13.9%, and two

of them maintained weight loss for several years.

Although the number of cases is too small to draw

definitive conclusions, it is not difficult to see the

significant effect of caffeine combined with

ephedrine. According to the study of Xiumei Wang

et al (Wang 2017), obese rats were divided into

control group, caffeine group, ephedrine group and

ephedrine combined with caffeine group for a period

of 21 days to observe the indexes, and the results in

Effect of Caffeine on Obesity and Its Application in the Treatment of Obesity

453

Table 2 were finally obtained. According to the

chart, the weight of the caffeine and ephedrine

groups showed little difference from that of the

normal control group, but the weight of the

ephedrine and caffeine combined group was

significantly lower than that of the obesity model

group. Therefore, caffeine and ephedrine alone had

little effect on weight loss. The combination of

ephedrine and caffeine resulted in significant weight

loss.

Table 2: Weight data of rats.

Group name 0 weeks weight 1 weeks weight 2 weeks weight 3 weeks weight

Normal Control group 188.23±10.81 251.01±8.55 308.37±20.23 358.03±24.56

Obesity model group 232.22±18.13 330.17±19.23 368.38±7.18 402.70±13.65

Caffeine group 224.42±12.24 243.09±19.03 301.03±22.51 340.36±20.03

Ephedrine group 228.41±18.13 256.31±17.01 310.37±18.53 351.14±17.18

Ephedrine and Caffeine

combined

rou

231.04±11.38 281.36±15.1 310.21±19.25 325.21±21.96

4 DISCUSSION

A large number of studies have confirmed the

positive effects of caffeine consumption in the

treatment of obesity, diabetes, etc. But whether

long-term consumption of caffeine will cause

damage to the body is not clear. And the effect of

suppressing appetite produced by caffeine has a

positive effect on weight loss, but it may cause

depression, anxiety and other psychological

conditions. In the next place, caffeine's half-life

(about 3-4 hours for a healthy adult) makes its

effects so short that it is not clear whether it has a

long-term lasting effect on obesity. Apart from that,

it remains to be seen whether long-term

consumption of large amounts of caffeine builds

tolerance and weakens weight loss, and whether it

leads to dependence.

5 CONCLUSIONS

From the current research, it can be concluded that

caffeine does have a certain effect on appetite and

metabolism, and because of these effects, it has a

certain effect on obesity, so it can be applied in the

treatment of obesity. But caffeine alone did not

result in the same weight loss as caffeine combined

with EGCG or ephedrine. Thus, caffeine alone as a

weight loss drug for the treatment of obesity is not

easy to achieve, but the combination of caffeine with

EGCG or ephedrine and other substances for the

treatment of obesity has great prospects.

In addition, during the research process of this

paper, there are too few literature about the"

influence of caffeine on appetite", so the mechanism

of action is not clear.

Currently, there is no complete system of drugs

for obesity treatment, and caffeine as a kind of

natural substance appears in people's lives almost

every day, it certainly is a good choice of weight

loss. But there is still a long way to go for caffeine to

be widely used to treat obesity, future research is

likely to focus on whether there is dependence,

resistance, and how to extend the duration action

should be researched as well.

ACKNOWLEDGEMENTS

I would like to thank Mr. Li Nuo and Mr. Wang

Xiaoying for their help and guidance in this study. I

would also like to thank my school shenyang

Agricultural University for the cultivation of me,

which has laid a solid foundation for me in the

professional field.

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