The methylxanthine caffeine is the most widely used stimulant drug in the world. The vast majority of American adults drink some type of caffeinated beverage on a daily basis, because of caffeine’s ability to fight fatigue and help us get through our busy schedules without skipping a beat.
One of the reasons caffeine is so good at this is that, unlike most nutritional supplements, caffeine readily crosses the blood-brain barrier, enabling it to directly affect the functioning of the neurons that coordinate your mental and physical activity.
Like its fellow methylxanthine theobromine, which we’ll be discussing in the next section, caffeine inhibits the action of adenosine, a nucleotide that builds up in brain tissue during your waking state and causes mental fatigue as it accumulates.
Fighting fatigue is a great thing for anyone trying to burn fat by dieting, since we all know that food elimination and caloric restriction can definitely make you feel tired and unmotivated.
But the methylxanthines do a lot more than just that. They also – caffeine in particular – can increase cellular energy production, which ultimately boosts your metabolism and causes you to burn more calories in a day.
Caffeine does this by inhibiting phosphodiesterase, an enzyme responsible for breaking down cyclic adenosine monophosphate, (cAMP), a messenger molecule that tells your cells to burn glucose and fatty acids for energy. Less phosphodiesterase means more cAMP, and in turn, a faster metabolism.[3-5]
Upregulation of cAMP via caffeine is particularly effective for increasing your rate of fat burning. Animal studies show that treatment with caffeine can increase fat burning by as much as 50%!
Diet is a great way to create a caloric deficit, but so is exercise – and caffeine can be a great help when it comes to working out, too!
Partly because of its effect on cellular energy production, caffeine can improve multiple aspects of athletic performance including strength, speed, and endurance.
Caffeine also increases attentiveness, alertness, reaction times, and working memory – all things that can suffer when you’re running a caloric deficit.[8-10]
These nootropic benefits are an important part of fat-burning supplements, because they can help improve adherence to your chosen fat loss regimen.
Cocoa Powder (Theobroma Cocoa L.)(Seed)
Cocoa powder is a potent source of epicatechin and other antioxidant, anti-inflammatory compounds.
The consumption of cocoa is associated with reduced inflammation, better circulation, decreased blood pressure, lower cholesterol, and better blood glucose control and insulin sensitivity.
Part of the magic here can be explained by the ability of cocoa’s polyphenol constituents to stimulate nitric oxide (NO) production,[12,13] which triggers vasodilation.
Cocoa alkaloids – nootropic, fat-burning
The alkaloids in cocoa play an important role, too – they can help decrease feelings of hunger, increase cellular energy production, upregulate thermogenesis, and even improve mood.[14,15]
Theobromine is the primary alkaloid in cocoa, and resembles caffeine in its metabolic effects. It inhibits the stimulation of adenosine receptors, just like caffeine, which improves alertness and motivation. Theobromine also increases cyclic adenosine monophosphate (cAMP) activity, leading to an increase in the number of calories, and particularly fatty acids, that you’ll burn in a day.[16,17]
Theobromine can also increase your body’s conversion of white adipose tissue (WAT) to brown adipose tissue (BAT). The main characteristic of BAT, compared to WAT, is its much higher mitochondrial density, which means it constantly burns calories as heat in a process called non-shivering thermogenesis.
One of the clearest patterns that emerges when you read the research literature on fat-burning ingredients is that all the best fat burners act by this mechanism – they all help convert WAT to BAT.
In fact, a person’s ratio of BAT to WAT inversely correlates with their obesity risk. The more BAT you have, the less likely you are to be overweight.[19,20]
Yohimbe Bark Extract 8% (Pausinystalia Yohimbe)
Yohimbe bark contains a powerful alkaloid called yohimbine, an alpha-2 adrenergic receptor antagonist. As such, yohimbine stimulates the sympathetic nervous system, which suppresses appetite and increases your body’s rate of fat burning[21,22] by inhibiting your body’s negative feedback mechanisms on noradrenaline production, which increases the amount of noradrenaline in your blood.
Noradrenaline is similar in its effects to adrenaline, so this increase comes with elevated heart rate, vasoconstriction, and increased alertness.
All of this probably sounds familiar, but be warned that yohimbine is strong. Ape Sh*t Heat uses a proprietary blend of ingredients, so we cannot tell you exactly how much yohimbine is in here, and given that 2 milligrams of yohimbine is the standard dose, a small difference in dosing can have pretty significant effects.
This is one of those ingredients that people either love or hate – plenty swear by its ability to improve mood and motivation, while others find that it gives them jittery, anxious energy that is uncomfortable and unproductive.
This individual variance is not merely anecdotal – peer-reviewed research backs up the idea that metabolism of yohimbine can be very different from one person to the next.
Because Ape Sh*t Heat is a capsule based supplement, taking a partial dose of this product to assess yohimbine tolerance is potentially tricky – one could break open the capsule and mix part of the powder in water, if tolerance is a real concern for you.
As always, consult with a licensed physician if you aren’t sure whether you should take yohimbine. With that said, we’re very excited to see Primeval working the trend in getting back to classic yohimbe — this isn’t rauwolfia / rauwolscine / alpha-yohimbine, which many will appreciate.
Grains of Paradise Extract (Aframomum melegueta)(seed)(Paradoxine)
Grains of paradise (known officially as Aframomum melegueta) is a pepper plant native to West Africa.
Extracts from grains of paradise are usually standardized for a bioactive constituent called 6-paradol, which is desired for its ability to beneficially alter the fat composition of the human body
How 6-paradol helps us get lean: white adipose tissue (WAT) vs brown adipose tissue (BAT)
There are two basic types of adipose (fat) tissue in the human body: white adipose tissue (WAT) and brown adipose tissue (BAT).
Although both contain stored energy in the form of body fat, they serve very different purposes: WAT is your body’s long-term energy reserve, used during famine conditions (low-calorie or zero-calorie environments) to ensure your survival. So long as your body has calories coming in, WAT tends to remain inactive.
BAT, on the other hand, is a metabolically active organ. It converts calories into heat during a process called non-shivering thermogenesis (NST), which is one of your body’s primary mechanisms for maintaining its core temperature when exposed to intense cold.
The more BAT you have, the more NST you’ll have in response to certain stimuli. Cold exposure is the primary activator of BAT – but as we’ll see, supplements like grains of paradise can also activate BAT.
Whenever BAT is activated, this contributes to your total daily energy expenditure (TDEE), which is defined as the number of calories your body burns in a day.
Put simply, BAT can speed up your metabolism.[27,28] A greater number of calories burned in a day means faster weight loss, assuming caloric intake is held constant (which it should be, if you’re trying to lose weight).
More than just weight loss: BAT and metabolic health
Here’s the thing though: even without weight loss, increasing your body’s BAT content can still significantly benefit your health.
The reason for this is that BAT consumes glucose and fatty acids during NST. This naturally leads to improved blood sugar control and blood triglyceride levels[29,30] because BAT removes those substances from your blood when it consumes them.
So why does BAT matter?
As you have probably guessed by now, the reason we’re talking about this is that the main bioactive constituent in grains of paradise, 6-paradol, has been shown to convert WAT into BAT.
More specifically, 6-paradol activates sirtuin 1 (SIRT1), which causes the browning of adipose tissue by deacetylating PPARγ.[31-33]
With everything we’ve discussed in mind, it’s not at all surprising that people with a higher ratio of BAT to WAT are generally in better cardiometabolic health, and have a significantly lower risk of type 2 diabetes compared to those with less BAT.
In one study that reviewed positron emission tomography-computed tomography (PET/CT) scans collected at the famous Sloan Kettering cancer hospital, researchers divided patients into two groups according to a simple scheme – patients that had some BAT were assigned to the BAT positive group, while patients with no detectable BAT were assigned to the BAT negative group.
They found that the BAT positive group had about half the risk of type 2 diabetes that the BAT negative group did – but they also had significantly lower risk of developing high cholesterol or triglycerides, coronary artery disease, cerebrovascular disease, congestive heart failure, and hypertension.
Considering how many aspects of health are downstream from metabolic health, this finding shouldn’t surprise anyone!
And the big takeaway for us, supplement formulators and consumers, is that increasing your BAT to WAT ratio with supplements like grains of paradise can be a high-impact strategy for improving body composition and overall health.
Grains of paradise studies
In one 2013 study, 19 healthy men between 20 and 32 years old were given a single 40 milligram dose of grains of paradise extract.
The data from the study showed that compared to the control group, the men who got grains of paradise burned more calories at rest.
It’s important to note that although all subjects who received grains of paradise showed an increase in metabolic rate, subjects with pre-existing BAT burned significantly more calories in response to grains of paradise than did subjects without BAT.
In other words, grains of paradise doesn’t just give you more BAT long-term – it also activates the BAT you already have.
In that sense, it’s kind of like cold exposure in a pill.
In another study, this one from 2014, women who took grains of paradise for a month saw significant reductions in their amount of visceral fat by the end of the study period. This is a good thing because visceral fat is particularly bad for you – visceral fat levels are tightly correlated with insulin resistance, metabolic syndrome and type 2 diabetes.
Visceral fat is in fact so causative of metabolic dysfunction that in one 2002 study, surgically removing visceral fat from aging rats – while level all other fat untouched – actually prevented age-related metabolic decline.
Needless to say, anything that helps us get rid of visceral fat is a welcome addition.
How BAT burns fat and glucose
Finally, let’s spend a little time talking about how BAT does all of this, because its mechanism of action is fundamental to overall health and wellness.
The answer is, in a word, mitochondria. BAT has way more mitochondria than WAT, which is actually where the name brown adipose tissue comes from.
When BAT and WAT samples are illuminated under a microscope, WAT looks white because it’s devoid of mitochondria, and thus translucent – BAT is actually so jam-packed with mitochondria that they block a significant amount of light, thus giving BAT a dark brown color.
Thus, converting WAT to BAT means creating new mitochondria to “brown” the WAT. And activating existing BAT basically means turning these mitochondria on.
The mitochondria inside BAT express a protein called uncoupling protein 1 (UCP1), which is key to their heat-generating and calorie burning potential.
Here’s a direct quote from a 2017 study on UCP1, explaining how it works:
“Brown adipose tissue (BAT) mitochondria are distinct from their counterparts in other tissues in that ATP production is not their primary physiologic role. BAT mitochondria are equipped with a specialized protein known as uncoupling protein 1 (UCP1). UCP1 short–circuits the electron transport chain, allowing mitochondrial membrane potential to be transduced to heat, making BAT a tissue capable of altering energy expenditure and fuel metabolism in mammals without increasing physical activity.”
Put in plain English, caloric expenditure is usually coupled to physical activity, meaning that if you want to burn more calories, you have to be more active.
Uncoupling protein 1 is so named because it uncouples caloric expenditure from physical activity: it causes your mitochondria to burn more calories regardless of whether you’re active or at rest.
Because of its pro-metabolic effect, UCP1 upregulation has been shown to protect against obesity and increase insulin sensitivity.
We harp on the importance of mitochondrial health all the time on the PricePlow blog, and hopefully you can see why. Still, this is just one way in which mitochondrial biogenesis can improve your health – it’s really just the tip of the iceberg when it comes to mitochondria.
We think any ingredient that’s been shown to upregulate mitochondrial growth or function should be given close attention.
So if you want to learn more about grains of paradise, read our article Grains of Paradise: Fat Fighting Spice of the Goddesses.