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The Ultimate Weight Loss Stack

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Weight-loss supplements are by far the most popular of all dietary supplement categories. They go by many names, such as diet pills, fat burners, stims, energy supplements, thermogenics, and GDAs, which can make it very confusing. Everyone wants a magic bullet that will help them lose fat. There are also hundreds of brands to choose from, each with its own special blend of ingredients that can help with weight loss, but understanding which ones to choose can be a challenge. To make sense of what to take for the best results, you need to understand the basics of how each ingredient works. As you get more advanced, you can then educate yourself on how each functions together. The ingredients in weight-loss supplements can stimulate different metabolic pathways in the body via thermogenesis (i.e., heat creation), appetite suppression, blood glucose management or increasing energy expenditure. Because there are multiple ways to stimulate weight loss, stacking ingredients is the best way to get maximum results. This review will give an overview of the different types of weight-loss supplements and the best ones to consider stacking with your diet and training program for best results.    

Thermogenic Supplements

The thermogenic category of weight-loss supplements’ primary focus is to increase the body’s thermogenic rate. This occurs when the body’s core body temperature increases. Why is this important? It means the body is burning extra calories, even while at rest. This is accomplished by increasing the release and activity of key fat-burning hormones, including norepinephrine, or stimulating metabolic pathways that oxidize fat. This means fat burning can occur for an extended period of time.

Thermogenic Supplement: MitoBurn (L-BAIBA) by NNB Nutrition

MitoBurn provides the key ingredient b-aminoisobutyric acid (L-BAIBA), a short non-protein amino acid by-product of the breakdown of the amino acids valine and thymine.1 This breakdown occurs in skeletal muscle during exercise via a biochemical mechanism called PGC-1a (peroxisome proliferator-activated receptor gamma co-activator 1-alpha) dependent mechanism.1 Because L-BAIBA is secreted by muscle cells, L-BAIBA is called a “myokine” and because it’s upregulated in response to exercise, it’s also referred to as an “exercise factor” that could be used as a signalling factor in the body.

One of L-BAIBA’s most interesting thermogenic effects is its ability to differentiate white adipose tissue (WAT) from brown adipose tissue (BAT) under in vivo and in vitro conditions in human stem cells.1 Although WAT is where your body stores fat, BAT is where the body burns fat. BAT is a highly metabolically active thermogenic fat that increases energy expenditure to generate heat. L-BAIBA was found to induce gene expression of mitochondrial uncoupling protein (UCP-1) via PGC-1a, as well as through the respiratory chain protein cytochrome C to differentiate adipocytes from WAT to BAT. These effects were dependent on activation of another receptor, PPARa, a transcription activator of free fatty acid (FFA) oxidation and BAT metabolism.2 Increased FFA oxidation, along with ATP production efficiency via UCP-1 may be the reason for decreased body fat accumulation via L-BAIBA.

L-BAIBA seems to hold promise for reducing body fat gain, increasing b-oxidation (fat burning) as well as a few other weight-loss benefits, including lowering bad cholesterol levels, improving insulin sensitivity and glucose tolerance, increasing ketone production, reducing the inflammatory response brought on by weight gain and having effects on satiating factors such as the appetite hormone leptin.    

How to Use MitoBurn (L-BAIBA)

Despite limited published research on L-BAIBA in humans, current research suggests that toxicity of L-BAIBA appears to be low. Many studies on mice given high doses of 100 milligrams per kilogram per day of L-BAIBA supplied in drinking water found positive outcomes.

When formulating a diet pill or if you’re looking for an ingredient to support weight loss, consider the L-isomer of L-BAIBA, which is more biologically active than D-BAIBA and more potent. MitoBurn is a potent L-BAIBA that’s stable in aqueous solutions and perfect for encapsulation. MitoBurn can be used once or twice a day in servings of 500 to 750 milligrams before exercise.

Thermogenic Supplement: Green Tea Extract

Although your Aunt Shirley may have sipped on green tea to help with longevity, green tea extract has been proven to be thermogenic, because of its rich antioxidant compounds known as polyphenols, specifically called catechins. The most metabolically active of these is epigallocatechin gallate (EGCG). 

This active ingredient works via short- and long-term intake. In the short term, EGCG blocks the COMT (catechol-O-methyltransferase) enzyme that can degrade the fat-loss hormone norepinephrine, increasing the amount of fat that gets used as fuel during exercise and rest.3 Blocking COMT results in prolonged effects of norepinephrine in the body, including increased energy expenditure and fat oxidation. Adding caffeine to this can have a synergistic effect. Caffeine blocks the enzyme cAMP, which also breaks down norepinephrine.

A recent meta-analysis found that green tea extract yielded significantly greater mean fat oxidation rates of 16 percent higher than a placebo.4 In addition, a double-blind crossover study found that intake of green tea extract before completing a bout of moderate intensity exercise resulted in 17 percent higher fat oxidation rates compared to a placebo.5        

Long-term intake has shown changes in the expression of fat metabolism genes including the upregulation of fat metabolism enzyme gene expression in the skeletal muscle and downregulation of adipogenic genes in the liver. It has been suggested that longer-term ingestion of green tea extract can keep energy expenditure high particularly during long periods of dietary restrictions.

In one study, healthy men given green tea extract for two months during which they also took part in a treadmill exercise program had 24 percent higher fat oxidation rates during exercise than the placebo group.6 In another study, daily consumption of green tea extract for 10 weeks plus a regular exercise program performed three times per week resulted in an increase in whole body fat utilization during exercise.7    

How to Use Green Tea

Although drinking green tea can provide many health benefits, to receive the thermogenic benefits of green tea, it’s best to supplement with an extract providing a concentrated dose of polyphenols. Choose a product that contains at least a standardized amount of 90 percent polyphenols and 45 percent EGCG. Although you can get caffeine-free green tea extract, because caffeine has a synergistic effect when combined with green tea, go for the stimulating version instead of the decaffeinated one! Doses range from 250 milligrams to 500 milligrams of green tea extract per day.   

Thermogenic Supplement: CaloriBurnGP (Grains of Paradise) by NNB Nutrition

Grains of paradise (also known as Aframomum melegueta) is an ancient spice with a similar composition to ginger. Animal research has shown that extracts of grains of paradise can induce sympathetic nervous system and BAT activity in a dose-dependent manner lasting up to three hours, as well as increased tissue temperature. These results showed that grains of paradise extracts (including the active compound 6-paradol) activate thermogenesis in BAT but are non-stimulatory.8 This means these effects are without the use of stimulants! It’s for this reason that grains of paradise has become one of the hottest weight-loss ingredients in the industry. NNB Nutrition is a company that’s been discovering better ways to engineer some of the most popular ingredients used in sports supplements. These guys are at the forefront of human performance research and invest millions of dollars into discovering new ingredients. They provide these to the top supplement companies in the industry, where you’ll see their ingredients in some of the most effective fat burners, pre-workouts, MCT powders, nootropics, GDAs and nitric oxide stimulators, to name a few.

NNB Nutrition’s chemical engineers created CaloriBurn GP, which is an ultra-pure form of grains of paradise using a proprietary extraction technology that’s able to preserve the bioactive compounds found in grains of paradise, including 6-paradol, 6-shogaol and 6-gingerol.

These three bioactive compounds found in CaloriBurn GP are provided in the exact levels that multiple human studies have shown to be effective in supporting metabolism and fat oxidation. In a single-blind, placebo-controlled study of 19 healthy young men, ingestion of 40 milligrams of grains of paradise resulted in a 400 percent increase in metabolic rate within 30 minutes! Additionally, participants taking grains of paradise experienced a 6 percent increase in energy expenditure compared to the control group.9

A second human study by the same researchers examined the effects of supplementing with grains of paradise extract daily for four weeks on energy expenditure and body composition in 19 healthy, overweight females in a single-blind placebo-controlled study.10 Participants taking grains of paradise experienced a 7 percent increase in metabolic rate and burned approximately 100 more calories daily compared to a placebo. They also lost roughly 250 percent more visceral fat than those taking the placebo.

How to Use CaloriBurn GP

CaloriBurn GP is standardized to one main bioactive compound and three synergistic compounds. The patented extraction process maintains the clinically validated constituents used in numerous studies. CalorieBurn GP is made from 100 percent natural sources without hazardous solvents, provides the effective compounds used in human studies and has GRAS (generally recognized as safe) status. CalorieBurn GP provides an authentic source; if a product lists extracted 6-paradol only, chances are it’s using a synthetic source, so be sure to look for the CalorieBurn GP if you’re using any supplement with grains of paradise in it. CalorieBurn GP can be used in 40- to 80-milligram doses one to three times per day.      

Thermogenic Supplement: Synephrine

Synephrine is an alkaloid extracted from the dried immature fruits of Citrus aurantium, also known as bitter orange. Citrus aurantium has traditional uses in Chinese medicine. Synephrine gained popularity because of its structural similarities to ephedrine, norepinephrine and epinephrine. Synephrine, however, has structural differences when it comes to its adrenergic receptor binding properties. In fact, it has little binding affinity to the receptors that ephedrine binds to, including beta-1 and 2 and alpha-1 and 2 receptors. It also has longer acting effects in the body.

Synephrine enhances thermogenesis by binding to the beta-3 adrenergic receptors, causing an increase in the body’s ability to break down fats to be used as energy. Synephrine also has a unique mechanism to assist in weight loss by enhancing carbohydrate metabolism. Synephrine facilitates cellular uptake of glucose in muscle cells, as well as in glycogenolysis, gluconeogenesis, glycolysis and oxygen uptake.

As a supplement, synephrine is often stacked with other weight-loss supplements such as caffeine for its synergistic combined effects. A research study showed that a 50-milligram single dose of synephrine in humans increased 24-hour resting metabolic rate (RMR) by 65 kilocalories relative to the placebo group.11 In the same study, synephrine plus the additional supplements naringin and hesperidin significantly increased RMR by 183 kilocalories, showing a synergistic effect when combined.  

How to Use Synephrine

Synephrine can be found on its own in the p-synephrine format, or often combined with other ingredients that increase its effectiveness, including the bioflavonoids naringin and hesperidin or even caffeine. P-synephrine is considered safe and free of most adverse side effects. P-synephrine can be supplemented in the range of 30 to 50 milligrams, taken two or three times daily.    

Energizing Supplements

Energy levels can fall when dieting. Energizing supplements can give you a boost, but that’s not all they can do. These supplements can help increase the breakdown of fat via lipolysis, allowing for the availability of more energy during workouts and greater caloric burning. This also results in preservation of lean muscle tissue, as the body switches from burning protein or carbs to burning fat as fuel.

Energizing Supplement: Caffeine

Perhaps one of the most used weight-loss supplements, and not just for its energizing effects, is caffeine. Caffeine blocks a key enzyme, cyclic adenosine monophosphate (cAMP), which is involved in degradation of norepinephrine, allowing it to stay active for longer. Not only do you get prolonged energy, you also get increased fat burning.

Caffeine consumption can promote a significant metabolism-increasing effect. In fact, one study showed that caffeine consumption at a dose of 100 milligrams resulted in a significant thermogenic effect even though test subjects had a habitual caffeine intake of 100 to 200 milligrams per day.12 The increase in energy expenditure didn’t return to baseline until three hours after consumption.

Caffeine also has a synergistic effect when combined with other fat-burning supplements such as green tea. Caffeine blocks a key enzyme involved in degradation of norepinephrine, a fat-burning hormone that gets stimulated by green tea. Caffeine’s action allows norepinephrine levels to remain elevated for longer periods.

Taking caffeine before a workout will enhance energy levels which is why it’s in nearly every pre-workout. Caffeine in the system can cause less reliance on glycogen, the muscles’ primary source of energy. Instead caffeine forces an increase in the mobilization of free fatty acids from storage to be burned as fuel. This means the body can burn off fat and hold onto more glycogen for muscles to use as energy.

Research has shown that following the ingestion of caffeine by cycling athletes, the process of glycogenolysis (which is the breakdown of the muscles’ energy source, glycogen) was decreased while fat oxidation or fat burning was increased.13 Thus, the body is provided with more fuel, resulting in longer workout performance and decreased time to fatigue.

How to Use Caffeine

Although coffee has been shown to be effective for weight loss and energy, consuming caffeine can be considered more effective. Caffeine supplements provide only the active caffeine, whereas coffee delivers other active ingredients that can actual reduce the stimulating and energizing effects of caffeine! There are many forms of caffeine, but the most commonly used is caffeine anhydrous. Supplementing with a minimum dose of 100 milligrams to upwards of 400 milligrams is considered reasonably safe. If stacking, less is more, and the dose will be dependent on other ingredients and the individual’s caffeine tolerance.

Energizing Supplement: L-Carnitine

This isn’t regarded as a traditional “energy supplement,” but when you understand the biochemical pathways it affects, you’ll see why we categorized it as such. Traditional carnitine is an amino acid that’s synthesized in the body by two amino acids, lysine and methionine. Carnitine plays a role in the transport of fatty acids in the mitochondria—the powerhouse cells—and this is how it increases energy. In the mitochondria, fats are broken down into ATP, which provides energy for all metabolic processes.14

Carnitine works by transporting long-chain acyl groups from fatty acids into the mitochondrial matrix, where it can go through oxidation to acetyl CoA, which is then used to drive the citric acid cycle to generate energy in the form of ATP. And if you weren’t sleeping through that biochemistry class, you’ll remember that ATP is the currency the body uses to fuel everything your body does. For our purposes, that also includes workout performance! This action can increase fat utilization while also enhancing energy levels, particularly for intense, endurance-type workouts such as cardio sessions.

As a supplement, carnitine is considered non-stimulating, helping preserve lean muscle tissue by switching the body to utilize available fat as fuel, decreasing glycogen or carbohydrate utilization. In a meta-analysis of available research, the effect of carnitine supplementation was evaluated for weight loss. 

Researchers found that test subjects who received carnitine lost significantly more weight and showed a decrease in body mass index (BMI) compared to the control group.15 In another systematic review and meta-analysis of 37 controlled clinical trials, L-carnitine supplementation significantly decreased body weight (weighted mean difference = -1.21 kg), body mass index (WMD = -0.24 kg/m), and fat mass (WMD = -2.08 kg).16

How to Use L-Carnitine

Carnitine can be found in weight-loss supplements but also pre-workout products, because it can help preserve muscle tissue and help the body switch to using fat for fuel while preserving muscle glycogen. Carnitine can be found in a few forms, including acetyl-L-carnitine, L-carnitine-L-tartrate and propionyl-L-carnitine. Doses range from 500 milligrams to a few grams.  

Glucose Disposal Agents (GDAs)

Lower blood glucose levels can help increase insulin sensitivity and even improve body composition. When insulin efficiency is impeded, the result can be weight gain and hormonal imbalances, triggering appetite and fat storage. Supplements that can help increase insulin sensitivity and lower blood glucose levels can be helpful for anyone who is looking to lose weight, especially when it comes to those individuals who are following keto or lower carb diets and need to reduce blood glucose levels significantly.     

Glucose Disposal Agents (GDAs): Chlorogenic Acid (via Green Coffee Bean Extract)

Most sports nutritionists wouldn’t classify green coffee bean extract as a glucose disposal agent (GDA), but let us explain why we do. Green coffee bean extract comes from unroasted coffee beans. The active ingredient in the coffee beans is chlorogenic acid (CGA), which is responsible for its weight-loss effects. Green coffee bean extract providing 45 to 55 percent chlorogenic acid can enhance energy metabolism and expenditure, decrease blood lipid levels, improve glucose tolerance and support weight management.17

Chlorogenic acid appears to work by a few mechanisms via inhibition of cAMP phosphodiesterase, resulting in upregulation of adenosine monophosphate activated protein kinase (AMPK), a regulator of energy metabolism that can stimulate fatty acid oxidation.18 Chlorogenic acid also inhibits pancreatic lipase, which results in a decrease in lipid absorption.19

In a 2013 review, chlorogenic acid was suggested to lower blood glucose levels and reduce carbohydrate absorption in the gut.20 It also seems to lower glycemic impact of foods. It’s been shown that chlorogenic acid is also a unique insulin sensitizer that potentiates insulin action and secretion.  

In a randomized double-blind, parallel-controlled trial, healthy overweight men and women received a high chlorogenic acid (369 milligrams) coffee or a control low chlorogenic acid (35 milligrams) coffee. This was consumed once daily for 12 weeks. When the results were in, abdominal fat, visceral fat, body weight and waist circumference significantly decreased in the high chlorogenic acid group.21      

How to Use Chlorogenic Acid

CGA can be found in blood glucose-lowering products and non-stimulating weight-loss products, but also stacked with ingredients that can increase thermogenesis. Typical human doses are in the range of 300 to 400 milligrams of the extract, providing 45 to 55 percent CGA, taken two or three times daily.

 

Glucose Disposal Agents (GDAs): Glucovantage (Dihydroberberine) by NNB Nutrition

Glucovantage contains dihydroberberine (DHB), which is actually the active metabolite of berberine. In fact, dihydroberberine is what your body converts berberine into during digestion! This bioactive plant has traditional uses in Chinese and Ayurvedic medicine. Berberine has been shown to help optimize blood glucose metabolism, insulin efficiency, lipid metabolism and body composition.

Berberine works by activating the AMPK enzyme, which acts as the central energy regulatory control switch, regulating how energy is produced and used in the body. AMPK activation can result in many different pathways to activate that are involved in maintaining energy homeostasis including regulating lipid, glucose and energy imbalances.22 One of AMPK’s targets includes glut1-mediated glucose transport, which in turn can increase insulin sensitivity and fat oxidation and inhibit fat cell growth.23

Berberine triggers AMPK activation and increases glycolysis (the breakdown of glucose) helping to decrease insulin resistance and decreased gluconeogenesis (the production of glucose in the liver).22

In a recent meta-analysis of 14 randomized trials in humans, treatment with berberine and lifestyle modifications showed significant hypoglycemic and cholesterol-lowering benefits.24 Supplementation with dihydroberberine was found to have similar benefits in animal models and required lower doses. Dihydroberberine appears to have enhanced bioavailability which is why we believe it’s superior to ordinary berberine. 

Dihydroberberine vs. Berberine 

In the body, after ingestion of berberine, gut microbes reduce it to dihydroberberine, which is then converted back to berberine after absorption by the intestines. Compared with supplementing with just berberine, dihydroberberine has five times more intestinal absorption, which means you would need to take five times the amount of berberine to get the same result as dihydroberberine.25 It’s also longer acting in the body—eight hours compared to just four hours with ordinary berberine!

In addition, dihydroberberine was found to enhance ketone activity when combined with exogenous ketone beta-hydroxybutyrate (BHB) when used at a 300-milligram dose.26 Dihydroberberine could potentially increase ketone activity by two to three times more than exogenous ketone supplements alone, making this a great supplement addition for those on keto diets!

How to Use GlucoVantage (Dihydroberberine)

When it comes to supplementing with berberine, because of its poor bioavailability and solubility, choose berberine’s active metabolite, Dihydroberberine. To produce this ingredient, NNB Nutrition extracted dihydroberberine from Berberis aristata. After extraction, a natural enzymatic process is used to convert it to no less than 97 percent dihydroberberine, in a process similar to that in the human gut. GlucoVantage is NNB Nutrition’s branded version of Dihydroberberine which can be found in stimulant-free weight-loss and blood glucose-regulating supplements, but it’s also a unique ingredient addition to ketogenic and low-carb supplements. Dosing is advised at 100 to 200 milligrams per serving, once or twice daily before eating.

Glucose Disposal Agents (GDAs): ZinjaBurn (Dehydrozingerone) by NNB Nutrition

ZinjaBurn contains the ingredient dehydrozingerone (DHZ), which is a natural phenolic compound obtained from the rhizomes of ginger. DHZ is structurally similar to the popular herb curcumin. In the body, curcumin is broken down into several bioactive fragments, including DHZ. Many sports supplement experts believe that DHZ could be an even more effective GDA ingredient than curcumin. DHZ has been shown to target AMPK, which contributes to its metabolic effects such as improved blood sugar levels, insulin sensitivity and increased glucose uptake. In a rodent study, DHZ was found to work by mitigating increases in fat gain and blood sugar levels when combined with a high fat diet through an AMPK pathway.27

Beneficial effects mediated by AMPK activation were seen in various tissues, such as skeletal muscle and adipocytes. Results showed that treatment with DHZ led to a 15 percent reduction in body weight and a 30 percent decrease in liver fat. DHZ also led to a reduction in body weight in mice fed a normal diet. Additionally, it was shown that supplementation with DHZ reduced blood glucose levels by 35 percent, insulin levels by 30 percent and the appetite hormone leptin by 35 percent in mice that received the high fat diet.   

Furthermore, it was confirmed that the fatty liver and peri-renal adipose tissue induced by an HFD were also significantly reduced in the group fed with DHZ compared to the HFD group.27 The findings indicate that DHZ may help support healthy fat metabolism and weight management.

How to Use ZinjaBurn (Dehydrozingerone)

ZinjaBurn provides a pure, highly bioavailable source of DHZ, which is more metabolically active than curcumin. Research on DHZ in humans is limited, but its toxicity appears to be low. A majority of mice studies show 100 milligrams per kilogram per day of DHZ is effective for weight and blood sugar management with a favorable safety profile.

DHZ can be used for weight loss and blood sugar support. It can be stacked with top weight-loss support ingredients, including MitoBurn (L-BAIBA), GlucoVantage (dihydroberberine) and CaloriBurn GP (grains of paradise). Dosing of ZinjaBurn (dehydrozingerone) DHZ should be two servings of 400 to 600 milligrams per day.

References
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