Guarana’s anti-obesity potential was the subject of a study that included researchers from UFRGS,  from the Universidad de la Costa, Colombia, and from the Federal University of Sergipe (UFS). From experiments with rats, scientists have proved that, in addition to preventing weight gain and fat accumulation, the plant can alleviate other conditions associated with obesity, such as insulin resistance. The results were published in the scientific journal Phytotherapy Research.

Rich in caffeine and with known antioxidant and anti-inflammatory properties, the extract from roasted guarana seeds has long been used as stimulant, aphrodisiac, tonic and also for weight loss. However, as the researchers claim that there was a lack of studies proving the supplement efficacy and security. “This extract is used in formulations (along with other compounds) for weight loss, but no one had proved the effect of this extract in its pure form,” says the study co-author Rafael Bortolin, professor at the Universidad de la Costa and collaborator at UFRGS Center for Oxidative Stress Studies.

During 18 weeks, 24 rats were fed with an ordinary western diet – developed by the group to induce obesity in the animals –, while another 24 consumed a low-fat control diet. Also, half of each group received guarana powder supplementation in a quantity that, if transposed to humans, would be equivalent to 300 milligrams per person per day.

According to Bortolin, the manufacturer of the guarana extract used in the research recommends a daily use of 1 to 3 grams, “however, we didn’t find scientific basis for this prescription. Also it is not easy to find out on the label what guarana is indicated for, but people in general use it because of its caffeine to feel alert and avoid sleepiness.” The use of guarana in these high doses, he explains, is to achieve a higher caffeine intake that keeps the user awake, similar to what happens whe we drink coffee. “The difference is that in order to lose weight, the use must be chronic, so it cannot be a high dose. Unlike a day when you have to study for a test and stay up all night, which is a momentary (acute) use when you can use a higher dosage.”

The scientists observed that guarana supplementation decreased weight gain and prevented excessive fat accumulation among animals fed with the Western diet. It also prevented other conditions related to obesity, as insulin resistance and dysregulation of adipokines – substances secreted by the adipose tissue, directly related to body fat distribution, and whose imbalance is associated with obesity and metabolic syndromes among other diseases.

After demonstrating guarana’s efficacy for the prevention and treatment of obesity, researchers began investigating its safety and possible adverse effects. “Many studies evaluating therapeutic potentials forget to evaluate the toxic potential of compounds (or extracts). We evaluated the toxic potential and identified no toxicity of guarana (in the concentration we used) in either the control group or the obese diet group,” explains Bortolin. It is important to emphasize, however, that effects of the excessive use of guarana were not studied. “It is quite possible that at higher doses it might exert some toxicity, because it has caffeine. Just as coffee can be toxic in high doses, so can guarana,” warns the researcher.

Finally, the mechanisms by which the substance acts to prevent weight gain were investigated. After verifying no quantity reduction of food intake, neither significant changes in the gut microbiota of the animals that consumed guarana, scientists analyzed changes in the brown adipose tissue – one of the two types of adipose tissue that we have in our body (the other is white).

While white adipose tissue has as its primary function the storage of energy, brown adipose tissue maintains body temperature and is the major site of thermogenesis in the mammals. Thermogenesis is a metabolic process that involves energy expenditure for heat production. A larger quantity of brown adipose tissue can, therefore, lead to a higher energy expenditure and, consequently, to weight loss.

“Thermogenesis is characterized by fat burning for heat production, instead of ATP [adenosine triphosphate, the molecule responsible for storing energy for the basic activities of cells]. It occurs because the mitochondria present in the brown adipose tissue have a lot of UCP, which is a protein that breaks down an electron gradient necessary for the production of ATP.  Thus, if we have a larger volume of this tissue, or if we have more mitochondria in this tissue, or if we have more UCPs in these mitochondria we can say that we promote thermogenesis, that is, we ‘activate’ the tissue,” explains Bortolin.

And that is what happened in the experiments. Guarana not only induced the expansion of brown adipose tissue but it also increased the number of mitochondria contained in it and the activation of proteins involved in the thermogenesis process. “It is known that the protein called by the acronym AMPK is related to energy expenditure and could contribute to the activation of brown adipose tissue. So, we investigated this protein and noticed that it was more phosphorylated (active) in the animals that consumed guarana. In addition, we also observed an increase in mitochondria number and UCP content. In summary, we saw that guarana was able to activate brown adipose tissue and we suggest that one of the mechanisms is via AMPK,” complements the researcher. It is worth reiterating, however, that this was an initial step. Tests on obese humans are still needed to confirm the study results.

Scientific Article

BORTOLIN, Rafael Calixto et al. Guarana supplementation attenuated obesity, insulin resistance, and adipokines dysregulation induced by a standardized human Western diet via brown adipose tissue activation. Phytotherapy Research, 13 mar. 2019.


The studies by David Costill in the late 1970s (2) showed that caffeine can increase the mobilisation of fatty acids from their stores. Fat is stored in several tissues but mostly in adipose tissues. The fatty acids are released from adipose tissue, can be transported to the muscle and be used as fuel. Some, but not all, studies show also an increase in fat oxidation with this elevation in fatty acids. However, it is not always true that an elevation in fatty acids levels in the blood also results in increased fat oxidation. This increase in fat oxidation was originally used to explain the performance benefits but it is now generally accepted that the increase in fat oxidation, does not spare muscle glycogen and improve performance. The performance enhancing effects of caffeine are predominantly through effects on the central nervous system.

New study finds increased fat oxidation with caffeine

The authors conducted a placebo controlled double blind study. Participants conducted two experimental trials. Before one of these they ingested 3 mg/kg of caffeine and before the other trial they ingested the same amount of a placebo. The capsules were ingested 1 hour before exercise. The participants (12 in total) exercised at fatmax intensity. This means that in an earlier test, the researchers had established the exercise intensity where these participants oxidised most fat. This is highly individual but on average was around 50% VO2max, a low-to-moderate exercise intensity.

During the hour of cycling, the subjects oxygen uptake and carbon dioxide production were measured and fat and carbohydrate oxidation were calculated from this. What the researchers found was an average total fat oxidation of 19.4 grams for the hour with placebo and 24.7 grams with caffeine. That is a whopping 27% more fat oxidation. They also found that there was no difference in energy expenditure and thus the increased fat oxidation meant that carbohydrate use was used (or carbohydrate was spared).

The researchers found an average total fat oxidation of 19.4 grams for the hour with placebo and 24.7 grams with caffeine. That is a whopping 27% more fat oxidation with caffeine.

Questions raised

The findings raise two questions. How does this relate to the rest of the literature, because we don’t want to make the mistake of drawing a conclusion on the basis of a single published study. The second question is what are the practical implications, if any?

The finding that caffeine can increase fat oxidation is not new. Several studies have shown this before, but it is important to realise that there are also many studies that did not see any effect of caffeine on fat oxidation. The different findings can at least party be explained by the exercise intensity used in the studies. A previous study by Juan del Coso’s research team (2) showed that effects of caffeine on fat oxidation could be observed at lower intensities but not at higher intensities (>80%VO2max).

There are other factors that could affect the outcomes as well, such as how trained the tested individuals were, the duration of the activity, the control of the diet before the trials and so on. But overall the findings of the study are in line with several previous studies and I would conclude that caffeine CAN in some situations increase fat oxidation. I was maybe a little surprised by the magnitude of change in this study, which seems a little greater than other studies. Of course, the effects may have been exaggerated by the fact that these studies were conducted in the fasted state (no breakfast), when fat oxidation is naturally high. As soon as we ingest a breakfast or eat carbohydrate, fat oxidation may be reduced by 30%. But the study is solid and well done and the authors need to be complimented. The issue is not the study, but may be the interpretation of the results by others.

Does it matter?

The million dollar question: does it matter? What are the practical implications of these findings? The authors are very careful not to speculate too much here. They just say that if people use caffeine for weight loss or for reducing body fat, they need to consider the negative effects of caffeine as well. I have seen social media reports who also linked the use of caffeine and the 27% increase in fat oxidation to weight loss. But let’s be clear: Weight loss will only occur when the energy expended exceeds energy intake. Caffeine did not increase energy expenditure, so you would still have to reduce intake to lose weight regardless of whether you burn more fat or not. The second observation is of course that even in this study where the effects on fat oxidation seem to be rather large, we are talking about a difference of only 5 grams of fat per hour of exercise. This means that in order to lose 1kg of body fat, one would have to exercise 200 hours!!

…..we are talking about a difference of only 5 grams of fat per hour of exercise. This means that in order to lose 1kg of body fat, one would have to exercise 200 hours!!

If an 80 kg person would like to lose 2% fat, it would take them a year, IF they exercised for an hour every day! So in terms of weight loss these findings are probably not important. Where the findings may potentially be important is that we stimulate fat oxidation more with caffeine, we therefore stress fat oxidation pathways more and we may adapt more. But how often would we need to do this in order to get significant adaptations that also translate to a performance or health effect? Without longer term studies such questions are difficult to answer.


  1. Ruiz-Moreno, C., Gutiérrez-Hellín, J., Amaro-Gahete, F.J. et al. Caffeine increases whole-body fat oxidation during 1 h of cycling at Fatmax. Eur J Nutr (2020).
  2. Costill DL, Dalsky GP, Fink WJ. Effects of caffeine ingestion on metabolism and exercise performance. Med Sci Sports. 1978 Fall;10(3):155-8. PMID: 723503.
  3. Gutiérrez-Hellín, J; Del Coso, J. Effects of p-Synephrine and Caffeine Ingestion on Substrate Oxidation during Exercise, Medicine & Science in Sports & Exercise: September 50(9): 1899-1906, 2018. doi: 10.1249/MSS.0000000000001653


This formula was developed for a starvation study by a group of scientists researching body fat loss. Everything indicates that it was used for the “Starvation Experiment in Minnesota, United States” (1944).

The formula was kept secret during the experiment and was also not disclosed in subsequent reports. However, some time later, in an unknown way, the formula was leaked from the saved files of the experiment and later it was replicated for new studies related to the loss of body fat. In this way, TRIGLY-X is created.

In the first experiment, human studies were conducted where some volunteers ended up with anorexia, starvation and extreme thinness changing their eating behavior forever. The details of this experiment were not published until years later. The extreme starvation and fat loss of the participants is believed to have resulted from administering the TRIGLY-X formula. Until today the information about its creation is unknown and it is only known that the formula is really effective in eliminating body fat. It should be taken with extreme caution and responsibility, strictly following the directions on the package. CAUTION: DO NOT LEAVE IN REACH OF CHILDREN.


Many of us will be stuffing ourselves silly from Thanksgiving to New Year’s Day.

But 70 years ago at this time, three dozen young men assembled in a laboratory under the football stadium at the University of Minnesota campus to do something quite different.

They were going to starve themselves for science and humanity.

The men had volunteered for what now is known as the Minnesota Starvation Experiment, a groundbreaking study that was conducted by U of M physiologist Ancel Keys.

Keys already had gained fame for developing the K ration, the portable food packet carried by paratroopers and other GIs in combat during World War II.

After the war, Keys would appear on the cover of Time magazine for establishing a link between saturated fat and heart disease and promoting the Mediterranean diet as a solution.

Recruiting conscientious objectors

But while WWII was still raging and the Allies slowly were grinding their way toward victory, Keys worked on a different problem: how to best feed starving people in newly liberated, occupied and war-torn countries.

Keys’ answer was an exhaustive, year-long experiment that would subject humans to “semi-starvation” in laboratory conditions. Then he would document how the test subjects responded to recovery diets.

The test subjects were recruited from the ranks of conscientious objectors who opposed being drafted into the military. They were pacifists who refused to kill for their country but who were willing to sacrifice themselves to help others.

For six months, the men went hungry. They became emaciated to the point that they resembled concentration camp survivors. Some went a little nuts.

The test subjects became obsessed with food. They collected cookbooks, recipes and kitchen gadgets and had nightmares about cannibalism. They lost interest in sex and became depressed, antisocial, lethargic and irritable.

When they went to the movies, they were most interested in the scenes when the actors were eating.

“I think for the first time, I read Proust because he had something to say about the joys of partaking in food,” said Daniel Peacock, 95, one of perhaps two or three of the original 36 starvation experiment subjects still alive.

“They kind of looked at food with an almost pornographic preoccupation,” said Todd Tucker, who wrote a book about the study, “The Great Starvation Experiment.”

The test subjects developed bizarre eating rituals and were tempted to eat garbage. They berated people who wasted food. Until the experimenters restricted it, one man chewed up to 40 packages of gum a day.

Two briefly were checked into psychiatric wards. One man cut off three of his fingers with an ax.

It could not be done today

Today, the experiment can be regarded as a case study of how much a person is willing to endure to stand up for one’s beliefs. And how much a researcher can ask someone to endure even if the result potentially could help millions.

“Here you are subjecting people to dramatic deprivation that really did cause them significant hardship,” said Sarah Tracy, a University of Oklahoma science history professor who is writing a biography of Keys.

The end result was a landmark examination of human starvation. The experiment is still consulted and cited by scientists, especially researchers studying eating disorders and the psychological impact of extreme hunger. It’s valued for its scientific rigor and because there is nothing else like it.

“Clearly, the experiment could not be done today,” said Henry Blackburn, an emeritus professor at the U who worked with Keys after the starvation experiment.

Blackburn, who took over as director of Keys’ Laboratory of Physiological Hygiene after Keys retired, said the starvation experiment met the ethical standards of the day.

But the experiment wouldn’t pass the current rules regarding fully informed consent and the welfare of test subjects, according to Blackburn.

“They were harmed temporarily,” he said.

In interviews in the years after the experiment, test subjects have said they were glad to have been chosen for the test and proud that they had participated.

During WWII, conscientious objectors who refused to be drafted into the military were put in something called the Civilian Public Service and assigned to work camps to do “work of national importance.” The work ranged from fighting forest fires to being attendants in mental institutions.

Conscientious objectors also were given the opportunity to be “guinea pigs” in medical experiments studying conditions such as malaria, typhus and pneumonia.

Keys sought volunteers for the starvation experiment with a pamphlet sent to the work camps around the country. The pamphlet had a picture of small children looking into empty bowls with a headline, “Will you starve that they be better fed?”

‘I wanted to risk my life’

Peacock was one of more than 400 young men who applied to be starved.

“It appeared to me as something more important to do than anything else I had been doing before the war,” said Peacock, a Quaker originally from Indiana. He now lives in Honolulu.

Conscientious objector Robert Villwock did road work in a public service camp in Virginia before he volunteered for the Minnesota experiment.

Villwock, of White Bear Lake, died in 2010. His widow, Dorothy Villwock, said that when her husband decided to become a conscientious objector, “His father was embarrassed and went around to the neighbors and apologized.”

“They were frustrated, the men in these camps, because they felt they weren’t doing really important work,” Dorothy Villwock said.

Author Tucker said the volunteers were idealistic and typically motivated by religious beliefs. They also were young men who wanted to prove their toughness at a time when conscientious objectors, or “conchies” as they were called in newspaper headlines, were suspected of being slackers or cowards.

“These guys all fought to be in the experiment,” Tucker said. “They considered themselves lucky to be in the experiment.”

“I wanted to do something that had a little more punch to it. I wanted to risk my life in some way and be of service,” said starvation volunteer Marshall Sutton, 96, a Quaker now living in Maryland. “I wanted to do something that was more adventurous.”

The experiment began Nov. 19, 1944. The 36 volunteers, with an average age of 25, were housed and tested in windowless rooms in Keys’ laboratory under the bleachers at Memorial Stadium.

The recruiting pamphlet said the volunteers would have access to an array of cultural activities in the Twin Cities and could take classes at a “School of Foreign Relief,” so they could “study as you starve.”

The pamphlet also noted the presence of a women’s dorm on campus “for those among us who are so extraordinarily versatile as to combine the qualities of a ‘guinea pig’ by day and a ‘wolf’ by night!”

Calories cut in half

Keys later would write that when the experiment began, there was a briefing “stressing the point that they were in for a hard time. All of them said they understood.”

“I was told, boy, this is going to be difficult,” Peacock remembered. “The general purpose of the experiment was pretty clearly understood.”

First, there was a three-month control period when the men received a normal diet of about 3,200 calories a day while researchers tested their strength, endurance, dexterity, hearing, sight, intelligence, personalities and even the potency of their semen.

“We were given some test every day of some kind,” Sutton said.

The tests continued when the six-month semi-starvation period began. But now, the calories were cut almost in half.

Instead of bacon, eggs, roast beef, mashed potatoes, gravy and chocolate sundaes, the men were fed twice a day from a monotonous menu believed to be similar to what many Europeans were trying to live on: bread, cabbage, rutabagas, turnips and macaroni.

Initially, the researchers “trusted us a little bit too much in the experiment,” Sutton said.

He said some of the test subjects were given jobs cleaning the dining room where the football players ate. The guinea pigs asked for different work because it was too tempting to eat the scraps left behind.

In addition to part-time work, the men were required to walk 22 miles a week.

Cheating incidents led the researchers to institute a “buddy system” requiring that the test subjects never leave the laboratory alone so they could help each other resist breaking the diet.

“I was tempted, of course,” Sutton said. “I did everything I could to keep my mind in order. I took upon it as a religious exercise.”

‘It changed our personalities’

The men eventually would would lose about 25 percent of their weight, dropping from an average of about 153 pounds to about 116 pounds.

Their hair fell out. Their skin roughened. Their hearts shrank in size, and their pulse rates dropped. They constantly felt cold. They found it uncomfortable to sit on hard surfaces. Some men collapsed during treadmill endurance tests.

Oddly, their hearing improved, an apparent confirmation of an old belief that hunger sharpens the senses.

But they felt like tired old men, irritated when they saw researchers climb stairs two steps at a time. They became withdrawn, humorless and possessive about their food.

“You not only lose vitality, you lose the camaraderie we had as a group,” Peacock said.

“It changed our personalities,” Sutton said. “We were always apologizing to each other for something we didn’t mean to do.”

They often finished their meals by licking their plates. They began to view normal-weight people as obese.

“I’m so hungry I could eat anything, but I’d start on the fat staff first,” one test subject wrote.

“We had periods of elation. Periods of deep depression. And our difficult traits came to the surface,” Sutton said.

He remembers that he lost interest in sex. When his girlfriend came to visit him, he took her out to dinner at a nice restaurant in Minneapolis just so he could watch her enjoy it. But when the food came, the girlfriend refused to eat.

“At the time, I felt a little upset with her. I paid good money for that meal,” Sutton said.

Even after the six-month semi-starvation period was over, the men couldn’t eat whatever they wanted. They continued to live in the laboratory for a three-month rehabilitation period while the researchers divided them into groups to see how different recovery diets worked.

“It was hard. For a year, they couldn’t take a mouthful of food that hadn’t been measured and weighed,” Dorothy Villwock said.

The experiment showed that adding vitamins or protein wasn’t crucial to recovery. Starving men simply needed to get more calories.

The day that all restrictions were lifted in late October 1945, “most of us had something planned out. Dan and I had our eye on a smorgasbord,” Peacock said of another test subject.

But Peacock said the two men bought food to go from the Minneapolis restaurant. They wanted to eat it in the lab “in case we overdid it, someone would be there to take care of us.”

Sutton traveled back home to the East Coast after the experiment and remembers having a couple of milkshakes every time the bus stopped.

The complete results of the study were documented in 1950 in a two-volume, 1,385-page work titled “The Biology of Human Starvation.”

But earlier summaries of the findings from the Minnesota experiment were published in an effort to help post-war relief efforts.

“Men and Hunger: a Psychological Manual for Relief Workers,” for example, advised that when dealing with starving people, “Never forget that anything related to food should be handled with respect and reverence.”

‘My protruding ribs were my battle scars’

Keys kept in touch with his former guinea pigs, who would become ministers and academics and relief workers after the experiment.

“He was impressed with them and their careers and their willingness to endure this,” said Keys’ daughter, Carrie D’Andrea.

After the war, Sutton did relief work for the American Friends Service Committee, distributing food to refugees in the Gaza strip.

“It made me sensitive to people who didn’t have enough food,” Sutton said of his year as a guinea pig.

Test subject Henry Scholberg made two trips to Poland for the United Nations, transporting livestock as a “sea-going cowboy.” He later became a professor and director of the Ames Library of South Asia at the University of Minnesota.

Another volunteer, Max Kampelman, finished his law degree at the U, worked as an aide for Hubert Humphrey and became a diplomat and arms-control negotiator for the Carter and Reagan administrations.

The test subjects returned Keys’ admiration and respect. They invited him and the other researchers to their reunions.

“I had a feeling this was an impressive group of men. Not that they were rich and famous,” said Dorothy Villwock, who attended the 50th reunion. “But this was an impressive group as far as their character.”

D’Andrea also was at that reunion. She said none of the test subjects were overweight, but some of the men admitted they always carried a candy bar with them.

They looked back at what they had endured with gratitude and a sense of accomplishment.

“I am proud of what I did. My protruding ribs were my battle scars,” Scholberg is quoted as saying in the study publication. “It was something great, something incomprehensible.”

Keys’ starvation laboratory, dubbed “the cage,” was torn down with the rest of Memorial Stadium in 1992. Keys died 10 years ago this week. He lived to 100.

Peacock said he would volunteer to starve again “provided that I would be that age again. I’m not about to do it at 95.”

Sutton said he’s always loved food. But now he’s almost blind. He depends on a walker and hearing aids. And in the past year, he said, he hasn’t eaten as much as he used to.

“My hunger is receding right now,” he said.