EDITION n° 1.
0 — AUGUST 2022
THE SCIENCE BEHIND
BLADE®
The Solution to the Struggle of Fat Loss
Written By:
Dr. David M. Gundermann, PhD, MSc
Director of Research & Development, Blue Star Nutraceuticals
© Blue Star Nutraceuticals — The information provided is for informational purposes only and is subject to change without notice.
This report does not constitute, either explicitly or implicitly, any provision of services or products by Blue Star Nutraceuticals, and
readers should determine for themselves whether or not the information herein is suitable for their needs.
THE SCIENCE BEHIND BL ADE ® EDITION n° 1.0 — AUGUST 2022
THE SCIENCE BEHIND BLADE ®
Body fat can be very stubborn to lose for many reasons. Most bodybuilders and fitness competitors can
attest that the process of burning off unwanted fat can sometimes be the most unpleasant phase of
fitness training. The reason stems from it being unnatural to willingly remove a rich source of energy
from the body. The body is designed to preserve extra calories as fat when nutrients are in abundance
and yet conserve those calories when fuel resources are low. This combination of physiological effects
makes the process of purposefully losing fat an uphill battle.
It is a naïve and oversimplified view that simply exercising more and eating less is an effective recipe for
fat loss, based on the “energy in” versus “energy out” principle. The premise of this idea is that net body
mass is a simple equation based on the balance on how much energy is consumed as food, and how much
energy is burned during exercise. The flaw in this principle is based on an incomplete understanding on
what all contributes to “energy out”. Exercise definitely contributes to energy expenditure, but it actually
plays a smaller portion than expected. This is where Blade® can assist.
Energy Expenditure Comes in Several Forms
There is a minimum rate of energy expenditure the body uses every day just to keep the body functioning
and cells alive, called the basal metabolic rate (BMR). Surprisingly, this rate is not always constant as it
can be modified daily, seasonally, and even environmentally. It is the most prominent variable for energy
expenditure, and modifying this will have a dramatic influence on overall energy expenditure. What the
BMR does not account for are the effects of any feeding or any movement.
The second influence on energy expenditure is the thermogenic effect of foods. This accounts for the
energy required to ingest, digest, absorb and store the nutrients in the diet. Considering the amount of
activity that is required for this process, a considerable amount of energy is expended during feeding. The
final influence is the amount of non-exercise activity. Activities of daily living make major unconscious
contributions to the overall energy expenditure. Environmental factors and lifestyle in a large part dictate
the extent of non-exercise activities, but the sympathetic nervous system plays a sizable role in non-
exercise energy expenditure.
While the “energy in / energy out” principle is true in theory, understanding how to manipulate the
“energy out” portion of the equation is quite complex with the overall metabolism seemingly going in the
opposite direction as intended. For instance, with dieting alone, the lack of food causes a drastic increase
in a hormone called Ghrelin. The elevation of Ghrelin is responsible for not only the increase in appetite
but also a decrease in metabolism, energy expenditure, and fat oxidation, resulting in the conservation of
fat. The reduction of food intake also diminishes the thermogenic effect of feeding as expected. Worst of
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THE SCIENCE BEHIND BL ADE ® EDITION n° 1.0 — AUGUST 2022
all however, is the decline in sympathetic nervous system (SNS) activity. This is the sensation of feeling
sluggish, empty, tired, lazy and unmotivated to do any physical activity. This decline in SNS activity is
responsible for the dramatic loss of non-exercise activity and also the guilt behind missing workout days
(see Figure 1).
Hypothalamus
Decrease in
food intake
Hypothalamus
Ghrelin Ghrelin ARC PVN
Appetite
Metabolism
SNS Sensitivity
Fat Conservation
Figure 1. Dieting causes an increase in Ghrelin release from the gut into the blood that crosses the blood brain barrier and into
the hypothalamus. Ghrelin activates the NPY/AgRP neurons in the arcuate nucleus (ARC) which in turn inhibit the MC4 receptors
in the paraventricular nucleus (PVN), which is responsible for satiety and energy balance. Dieting therefore results in increased
appetite, lower rates of metabolism, lower SNS sensitivity and fat conservation.
Through supplementation with Blade®, these variables can be addressed to assist with a diet plan to make
fat loss effortless and more substantial. The ingredients in Blade® have been scientifically and clinically
shown to be a positive factor in fat loss on five fronts. When combined together, these five mechanisms
synergistically allow for the ultimate environment to achieve maximal fat loss.
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THE SCIENCE BEHIND BL ADE ® EDITION n° 1.0 — AUGUST 2022
1. Increased Lipolysis
The very first place to start with fat loss is breaking down the fat tissue where it resides in the fat cells.
The process of lipolysis is the enzymatic breakdown of fat stored as triglycerides into individual free fatty
acids (FFA). This process is the rate-limiting step for the removal of unwanted fat and is governed by SNS
activity. Typically, SNS activity leads to the production of the hormones epinephrine and norepinephrine
(N.E.) that bind to β-adrenergic receptors in fat cells to trigger a cascade of signals to result in an increase
in lipolysis (Figure 2). Therefore, using ingredients that have been shown to enhance SNS activity, N.E.
availability, or increase lipolysis are beneficial for this purpose.
Fat Cell
Triglycerides
N.E.
Lipolysis
AC cAMP HSL
N.E.
Free Fatty Acids
Figure 2. Norepinephrine (N.E.) stimulates the breakdown of fat (lipolysis) through the β-adrenergic signaling pathway (AC:
Adenylate cyclase, cAMP: cyclic adenosine monophosphate, HSL: hormone sensitive lipase).
Green tea extract is another ingredient that increases the concentration of N.E. but by another mechanism.
A subclass of green tea flavonoids called tea catechins have been shown to have long lasting effects on
the inhibition of the enzyme that degrades N.E. called COMT. Research with green tea extract show that
inhibition of COMT can allow N.E. to stay elevated for at least 24 hours. Green tea extract on its own has
been shown to increase N.E. concentration levels by 37%.
Capsiate is a natural capsinoid from CH-19 sweet peppers. Structurally similar to capsaicin, it binds to
the same receptors that capsaicin does to activate the SNS to produce an increase in N.E. that has been
shown clinically to yield an 89% increase in free fatty acids.
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THE SCIENCE BEHIND BL ADE ® EDITION n° 1.0 — AUGUST 2022
Rob Riches
Blue Star Nutraceuticals® Athlete
Caffeine also activates multiple pathways to induce lipolysis. Firstly, caffeine competes with a compound
called adenosine. Adenosine acts on α1-receptors to induce drowsiness by decreasing the release of
N.E. Caffeine effectively increases N.E. by inhibiting this pathway. Caffeine plays an additional role in
prolonging the effect of lipolysis by inhibiting an enzyme that interferes with the β-adrenergic signaling
pathway.
Advantra Z® takes a more direct approach. Using an extract from the bitter orange known as Citrus
aurantium. Advantra Z® is standardized to the active ingredient, p-synephrine. Among several beneficial
features, p-synephrine can independently and directly bind to β-receptors to induce lipolysis.
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THE SCIENCE BEHIND BL ADE ® EDITION n° 1.0 — AUGUST 2022
The combination of each of these ingredients results in the fast acting, long lasting, and dramatic
increases in N.E. concentrations through synergistic mechanisms to provide the highest possible
increase in lipolysis.
2. Enhanced Lipid Transport and Oxidation
Freeing up fatty acids is the rate-limiting step for fat burning but does not actually burn any fat. If left
unprocessed, individual FFA can resynthesize into triglycerides if they are not quickly burned (oxidation).
Fat oxidation is a long and complex process that occurs primarily in the mitochondria of muscles. However,
the mitochondrial membrane is completely impermeable to fatty acids. Using a series of transporters,
carnitine is an indispensable carrier of FFA across the mitochondrial membrane. Improving the pool
of muscle carnitine through supplementation of L-carnitine can allow for enhanced FFA transport into
mitochondria and thus lead to greater fat oxidation.
The influence of green tea extract alone is capable of increasing fat oxidation by 35%, leading to an
average of 26.8g of fat oxidation over a 24-hour period. The combination of L-carnitine and green tea
ensures that a maximal quantity of free fatty acids make it into the mitochondria, and the fat burning
process is continually turned on for 24 hours.
CH-19
Sweet
Pepper
Green Tea Extract
TRPv1 Channels
ACC
Chalcineurin
Fat Cells
FAS
Adipogenesis Fatty Acid Synthesis
Figure 3. CH-19 sweet pepper and green tea extract inhibit independent cell signaling pathways to inhibit adipocyte production
(adipogenesis) and fat-cell growth (fatty acid synthesis).
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THE SCIENCE BEHIND BL ADE ® EDITION n° 1.0 — AUGUST 2022
3. Decreased Adipogenesis and Fatty Acid Synthesis
Attacking the already existing fat is important for fat loss, but it is crucial to attenuate the deposits of new
fat. The synthesis of fat can occur on two major levels: the production of new fat cells (adipogenesis)
and the growth of fat cells caused by the synthesis of fatty acids within them (fatty acid synthesis).
Suppressing the adipogenesis and/or fatty acid synthesis will help contribute to a leaner physique.
The regulation of these processes can be complex. Specific transcription factors known as PPARγ and
C/EBPα primarily promote adipogenesis. Simply put, negatively effecting PPARγ or C/EBPα will help
reduce the production of new fat cells. As illustrated in (Figure 3), Capsiate activates a capsaicin receptor
called TRPv1 that ultimately inhibits adipogenesis through the inhibition of PPARγ and C/EBPα.
The process of fatty acid synthesis is initiated and committed by the enzyme Acetyl-CoA-Carboxylase
(ACC), which is then carried out by the enzyme Fatty Acid Synthase (FAS). Inhibition of either of these two
enzymes will suppress the accumulation of fat into fat cells. Green tea extract can inhibit ACC and thus
suppress the committed step of fatty acid biosynthesis. Specifically, the research data indicates that one
specific tea catechin, named Epigallocatechin gallate (ECGC) is responsible for this effect. Furthermore,
capsiate has been shown to reduce fatty acid synthesis through the reduction of FAS activity. Collectively,
these studies show improvements over a 9 day period that inhibit the increases in adipocyte number by
34% and total triglyceride content by 54%.
4. Increase in Overall Metabolic Rate / Thermogenesis
Manipulating overall energy expenditure in the absence of chronic exercise is not easy. However, certain
compounds can help improve energy expenditures by either improving BMR or exploiting a tissue that is
mostly dormant in the body called brown adipose tissue (BAT). BAT is a type of fat tissue but is not to be
confused with the undesirable fat targeted to be lost. BAT is a highly metabolic tissue that functions by
burning calories for heat (thermogenesis) rather than for activity. This means that simply increasing BAT
activity can help burn fat without requiring an increase in activity at all. For many years, it was believed
that only infants had BAT and humans lost BAT after becoming adults, but recent evidence shows that
adults still have adequate BAT that can be used to burn through excess energy. BAT uses a specialized
set of proteins called uncoupling proteins (UCP) that are responsible for the conversion of energy to
heat. The following ingredients in Blade® have been associated with thermogenesis.
Caffeine is a potent thermogenic compound that has been repeatedly shown to improve the basal
metabolic rate by at least 6% for the first 4 hours after consumption. Caffeine is also documented to
increase fat metabolism by 42%.
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THE SCIENCE BEHIND BL ADE ® EDITION n° 1.0 — AUGUST 2022
Green tea extract has also been shown to stimulate BAT thermogenesis, especially when combined
with caffeine to a degree greater than caffeine alone. It is proposed that the catechin-polyphenols of the
green tea are responsible for stimulating thermogenesis at various control points. In result, green tea
extract has been shown to increase total energy expenditure by 4.5% during waking hours alone.
Capsiate has been shown in studies to upregulate UCP, while exhibiting an increase in body temperature
and energy. In fact, a clinical study of 80 participants who supplemented with capsinoids 30 minutes
before morning and evening meals showed that the mechanism of activating UCP was preferential to
the abdominal fat region. This particular study observed a significantly greater loss of fat mass in the
abdominal region when relative to the overall body fat loss when compared to a placebo group using
caloric restriction alone (Figure 4).
Overall FAT Abdominal FAT
-0.0 -0.0
Change of abdominal FAT (%)
Change of percent FAT (%)
-0.2 -0.2
-0.4
-0.4
-0.6
-0.6
-0.8
-0.8
-1.0
-1.0 -1.2
-1.2 -1.4
-1.4 -1.6 Placebo
Capsinoids
Figure 4. Clinical study with 80 participants indicates that supplementation with capsinoids is significantly associated with
significantly greater decreases in abdominal fat loss relative to overall fat loss.
At least nine studies have investigated the effects of p-synephrine on metabolic rate and energy
expenditure. All of which showed an increase in resting metabolic rate, energy expenditure and modest
increases in weight loss within 6-12 weeks. Due to its mechanism in increasing fat oxidation, improving
SNS activity, and overall metabolic rate, research on Advantra Z® has also observed that exercise was
perceived as less difficult by over 80% of test participants.The ability to manipulate metabolic rate, non-
exercise energy expenditure, SNS activity, and improve upon the desire to exercise is a huge advancement
for supplementation. This leaves just one variable left to address.
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THE SCIENCE BEHIND BL ADE ® EDITION n° 1.0 — AUGUST 2022
5. Decreased Appetite
The final component to achieving a lean physique is accounting for the “energy in” portion of the equation.
While the mechanisms of Blade® so far can assist with augmenting fat breakdown, improving metabolic
rate and increasing SNS sensitivity, the remaining negative characteristic to dieting is the effects of
appetite. Without curbing appetite, fat loss still remains to be an uphill battle. Capsiate has been shown
to affect eating behaviour on two different levels. Studies show not only a reduction of voluntary calorie
consumption by 14%, but a significant trend to crave healthier foods. Evidence suggests that capsiate
also increases the “feel-good” hormone called dopamine in the brain, which contributes to making better
nutritional decisions during the unpleasant experience of dieting.
CONCLUSION
The formulation of Blade® is the only formula that addresses every possible angle required for a fat
loss process. Blade® uses only the most efficient, natural health ingredients that overlap with several
attributes relating to targeting fat breakdown, preventing fat gain, improving metabolic rate, increasing
the susceptibility for activity, and managing appetite. Simply put, the ingredients in Blade® are backed by
science unlike any other fat burner on the market.
Rob Riches
Blue Star Nutraceuticals® Athlete
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THE SCIENCE BEHIND BL ADE ® EDITION n° 1.0 — AUGUST 2022
References
Belza A, Toubro S, Astrup A. The effect of caffeine, green tea and tyrosine on thermogenesis and energy intake. Eur J Clin Nutr. 63;
57-64, 2009.
Birerdinc A, Jarrar M, Stotish T, Randhawa M, Baranova A. Manipulating molecular switches in brown adipocytes and their
precursors: A therapeutic potential. Prog Lipid Res. 52; 51-61, 2013.
Bloomer RJ, Canale RE, Shastri S, Suvarnapathki S. Effect of oral intake of capsiacinoid beadlets on catecholamine secretion
and blood markers of lipolysis and healthy adults: a randomized, placebo controlled, double-blind, cross-over study. Lipids Health
Dis. 9; DOI: 10.1186/1476-511X-9-72, 2010.
Diepvens K, Westerterp KR, Westerterp-Plantenga MS. Obesity and thermogenesis related to the consumption of caffeine
ephedrine, capsaicin, and green tea. Am J Physiol Regul Integr Comp Physiol. 292; R77-R85, 2007.
Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J. Efficacy of green tea extract rich
catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 70; 1040-
1045, 1999.
Dullo AG, Seydoux J, Girardier L, Chantre P, Vandermander J. Green tea and thermogenesis: interactions between catechin-
polyphenols, caffeine and sympathetic activity. Int J Obes Relat Metab Disord. 24; 252-258, 2000.
Galitzky J. Taouis M, Berlan M, Riviere D, Garrigues M, Lafontan M. alpha2-Antagonist compounds and lipid mobilization:
evidence for lipid mobilizing effect of oral yohimbine in healthy male volunteers. Eur J Clin Invest. 18; 587-594, 1988.
Grasing K, Sturgill MG, Rosen RC, Trout JR, Thomas TJ, Kulkarni GD, Maines P, Seibold JR. Effects of yohimbine on autonomic
measures are determined by individual values for area under the concentration-time curve. J Clin Pharmacol. 36; 814-822,
1996.
Hsu CL, Yen GC. Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells. J Agric Food Chem.
55; 1730-1736, 2007.
Imaizumi K, Sato S, Kumazawa M, Arai N, Aritoshi S, Akimoto S, Sakaibara Y, Kawashima Y, Tachiyashiki K. Capsaicinoids-induced
changes of plasma glucose, free fatty acid and glycerol concentrations in rats. J Toxicol Sci. 36; 109-116, 2011.
Kao YH, Hiipakka RA, Liao S. Modulation of obesity by green tea catechin. Am J Clin Nutr. 72; 1232-1234, 2000.
Musso NR, Vergassola C, Pende A, Lotti G. Yohimbine effects on blood pressure and plasma catecholamines in human
hypertension. Am J Hypertens. 8; 565-571, 1995.
Neal JW, Clipstone NA. Calcineurin Mediates the Calcium-dependent Inhibition of Adipocyte Differentiation in 3T3-L1 Cells. J
Biol Chem. 227; 49776-49781, 2002.
Ohnluki K, Haramizu S, Watanabe T, Yaxzawa S, Fushiki T. CH-19 sweet, nonpungent cultivar of red pepper, increased body
temperature in mice with vanilloid receptors stimulation by capsiate. J Nutr Sci Vitaminol. 47; 295-298, 2001.
Ratamess NA, Bush JA, Kang J, Kraemer WJ, Stohs SJ, Nocera VG, Leise MD, Diamond KB, Campbell SC, Miller HB,
Faigenbaum AD. The effects of Supplementation is p-Synephrine Alone and in Combination with Caffeine on Metabolic, Lipolytic,
and Cardiovascular Responses during Resistance Exercise. J Am Coll Nutr 35; 657-669, 2016.
PAGE 10
THE SCIENCE BEHIND BL ADE ® EDITION n° 1.0 — AUGUST 2022
Reinbach HC, Smeets A, Martinussen T, Moller P, Westerterp-Plantenga MS. Effects of capsaicin, green tea and CH-19 sweet
pepper on appetite and energy intake in humans in negative and positive energy balance. Clin Nutr. 28; 260-265, 2009.
Rosen ED, Speigelman BM. Molecular Regulation of Adipogenesis. Anny Rev Cell Dev Biol. 16; 145-171, 2000.
Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 6; 661-671,
2000.
Stohs SJ, Preuss HG, Keith SC, Keith PL, Miller H, Kaats GR. Effects of p-Synephrine alone and in Combination with Selective
Bioflavonoids on Resting Metabolism, Blood Pressure, Heart Rate and Self-Reported Mood Changes. Int J Med Sci 8; 295-301,
2011.
Stohs SJ, Preuss HG, Shara M. A Review of the Human Clinical Studies involving Citrus aurantium (Bitter Orange) Extract and
its Primary Protoalkaloid p-Synephrine. Int J Med Sci. 9; 527-538, 2012.
Stohs SJ, Badmaev V. A Review of Natural Stimulant and Non-stimulant Thermogenic Agents. Phytother Res. 30; 732-740,
2016.
Szallasi A, Blumberg PM. Vanilloid (Capsaicin) Receptors and Mechanisms. Pharmacol Rev. 51; 159-211, 1999.
Tschop M Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 19; 908-913, 2000.
Whiting S, Derbyshire E, Tiwari BK. Capsaicinoids and capsinoids. A potential role for weight management? A systematic review of
the evidence. Appetite. 59; 341-348, 2012.
Y D Cheung, D B Barnett, S R Nahorski. [3H]Rauwolscine and [3H]yohimbine binding to rat cerebral and human platelet
membranes: possible heterogeneity of alpha 2-adrenoceptors. Eur J Pharmacol. 15;84(1-2):79-85, 1982.
C Pimoule, M S Briley, C Gay, H Loo, D Sechter, E Zarifian, R Raisman, S Z Langer. 3H-Rauwolscine binding in platelets from
depressed patients and healthy volunteers. Psychopharmacology (Berl). 79(4):308-12, 1983.
T R Norman, N M Kimber, F K Judd, G D Burrows, I M McIntyre. Platelet 3H-rauwolscine binding in patients with panic attacks.
Psychiatry Res. 22(1):43-8, 1987.
N B Shepperson, N Duval, R Massingham, S Z Langer. Pre- and postsynaptic alpha adrenoceptor selectivity studies with yohimbine
and its two diastereoisomers rauwolscine and corynanthine in the anesthetized dog. J Pharmacol Exp Ther. 219(2):540-6, 1981.
J C Doxey, A C Lane, A G Roach, N K Virdee. Comparison of the alpha-adrenoceptor antagonist profiles of idazoxan (RX 781094),
yohimbine, rauwolscine and corynanthine. Naunyn Schmiedebergs Arch Pharmacol. 325(2):136-44, 1984.
B Szabo, L Hedler, K Starke. Peripheral presynaptic and central effects of clonidine, yohimbine and rauwolscine on the sympathetic
nervous system in rabbits. Naunyn Schmiedebergs Arch Pharmacol. 340(6):648-57, 1989.
M F Callahan, M Beales, G A Oltmans. Yohimbine and rauwolscine reduce food intake of genetically obese (obob) and lean mice.
Pharmacol Biochem Behav. 20(4):591-9, 1984.
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of Blue Star Nutraceuticals®.
The information provided is for informational purposes only and is subject to change without notice. This report does not constitute,
either explicitly or implicitly, any provision of services or products by Blue Star Nutraceuticals, and readers should determine for
themselves whether or not the information herein is suitable for their needs.
About The Author
Dr. David Gundermann is an award winning nutritional product development
scientist, clinical researcher, and known expert in muscle health and metabolism. He
developed his passion for health & fitness at a very early age growing up in a family
of accomplished competitive athletes.
As Director of Research and Development at Blue Star Nutraceuticals®, he leads
all efforts concerning product formulation, key ingredient research, flavor science,
long-term scientific assessment, and proprietary development.
Dr. David Gundermann, PhD, MSc
Blue Star Nutraceuticals Inc.
3-5 Edinburgh Road South
[email protected]Guelph, Ontario, N1H 5N8 www.bluestarnutraceuticals.com
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