Diablo is ANS’s powder-form fat-burner which contains a wide array of ingredients, some stimulant and some non-stimulant.
The primary physiological role of Carnitine, other than being a component of proteins, is to transport fatty acids into the mitochondria where they are burned for energy through a process known as beta-oxidation. Carnitine deficiency has been shown to result in hindered fat-burning capacity. Because it plays such an important role in the fat-burning process, Carnitine supplementation is alleged to burn fat via increasing the transport of fatty acids to the mitochondria. However, research has indicated that it may not be that simple.
A 2002 study, published in “Metabolism”, found that Carnitine supplementation (1g/day) increased fatty acid oxidation rates in humans without Carnitine deficiency. A 2004 study from the same journal found that L-Carnitine supplementation (3g/day) increased fatty acid oxidation in overweight subjects while as well.
However, a 2005 study, published in the “International Journal for Vitamin and Nutrition Research”, found that Carnitine supplementation failed to influence weight-loss in rats. The results of this study were in-line with an earlier (2002) study in which L-Carnitine supplementation (4g/day) failed to influence fat mass, body mass, or resting lipid utilization in moderately obese women.
A more recent (2010) study found that Carnitine supplementation did favorably influence fatty acid utilization in rats, though this study did not measure fat mass post-supplementation.
Ultimately, Carnitine does possess the mechanisms by which it should burn fat (via increased utilization of fatty acids), though supplementation has failed to result in fat-loss in animals and humans.
Choline, once inside the body, is converted into the neurotransmitter Acetylcholine which is associated with many functions including (but not limited to) memory, attention, and muscle control. It is the neurotransmitter most closely associated with the “mind-muscle connection” (although this may be something of an over-simplification), and therefore of much interest to athletes and bodybuilders alike. While certain forms of choline may be associated with increased muscular power output (namely Alpha GPC), Choline Bitartrate is generally considered the least bioavailable choline source, though oral doses of 1000-2000mg have still been shown to increase serum choline levels significantly.
While Choline doesn’t really have an inherent fat-burning properties, it may serve as a means to preserve brain function during a calorie-restricted diet, and can possibly enhance exercise performance.
GREEN COFFEE EXTRACT (AS COFFEA CANEPHORA ROBUSTA) (BEAN):
The primary active component found in Green Coffee Extract is Chlorogenic Acid which has recently become a popular weight-loss option for stimulant-adverse individuals.
A 2010 study from “Food and Chemical Toxicology” found multiple anti-obesity effects of Chlorogenic Acid administered to mice including increase beta-oxidations (fat-burning). While this increase in fat-burning may have been partially responsible for the significant weight-loss noted in rodents, Chlorogenic Acid has an alternative mechanism of action that applied for to humans: Inhibition of carbohydrate absorption.
A 2007 study, published in the “Journal of International Medical Research”, found that 12 weeks of Green Coffee (450-500mg Clorogenic Acid) supplementation resulted in a reduction (6.9%) in glucose absorption in healthy volunteers. Researchers also noted average weight loss of 5.4 kg (almost 12 lbs) over the duration of the study in the group receiving the Green Coffee Extract.
A 2006 study, this time using a smaller dose of Green Coffee Extract (yielding 140mg Chlorogenic Acid), found no such weight-loss benefit over a 12 week period. The obvious difference between these two studies is that the dose of the first (positive) study was about 3 times the dose used in the second (negative) study.
A 2012 study found that adults who consumed GCE (containing about 315mg Chlorogenic Acid) daily lost an average of 8kg with the average reduction in body fat being about 4%.
Though Green Coffee Extract has shown mixed results in various studies, clear efficacy has been demonstrated at high enough doses (at least 300mg Chlorogenic Acid). Diablo contains 150mg of Green Coffee Extract standardized to 50% Chlorogenic Acid, so one serving contains 75mg. Effective doses of Chlorogenic Acid are atleast 200-300mg daily, so multiple servings must be consumed.
AdiLase is a patented form of Hemerocallis fulva extract which is alleged to aid in fat-loss via reversal of catcholamine-resistance in fat-cells. A 2009 study, published in “Experimental Biology and Medicine”, found that Hemerocallis fulva extract was able to reduce catecholamine-resistance in rat adipocytes (fat-cells), ultimately augmenting the effects of Noradrenaline-induced lipolysis. Unfortunately, this is the only study investigating the potential lipolytic effects of Hemerocallis fulva, making it difficult to determine how effective it may be in humans.
Caffeine triggers the release of Catecholamines (i.e. Noradrenaline, Adrenaline, Dopamine) which, in addition to enhancing focus and alertness, are inherently pro-lipolytic. Unfortunately, habitual Caffeine consumption tends to lead to tolerance, making it less and less effective as time goes on. That being said, Caffeine may be synergistic with other stimulants and tends to increase perceived energy, leading to more intense workouts. Diablo contains an undisclosed amount of Caffeine, though we’d estimate about 100mg.
As far as Phenylethylamine’s direct effects on weight loss, studies are more or less non-existent. However, PEA triggers the release of Catecholamines (Noradrenaline, Adrenaline, etc.) the general physiological reaction of which is activation of the beta-adrenergic receptors which induce lipolysis. So the mechanism by which PEA may induce weight loss is theoretically sound, just not documented. Because the effects are generally short-lived, it is hardly a miracle weight-loss supplement on its own, but combined with compounds such as Hordenine (which blocks the rapid oxidation of PEA in the brain) the effects can be amplified and practically relevant. Diablo contains an undisclosed amount of B-PEA.
Evodiamine is a plant extract which appears to mimic the thermogenic effects of Capsaicin in rats. However, no human studies have been published at this time testing the effects of the extract on humans. Due to the lack of human studies available, we cannot determine with any considerable degree of certainty, the efficacy of Evodiamine.
Higenamine has been shown (in vitro) to be a beta-adrenergic receptor agonist as well as a weak alpha-adrenergic receptor antagonist, the same basic mechanisms of action by which Synephrine and Ephedrine work. By activating beta-receptors while simultaneously (albeit weakly) blocking alpha-receptors, Higenamine can potentiate the effects of Noradrenaline-releasing agents such as Caffeine and facilitate more fat-loss than could otherwise normally be achieved through exercise alone.
Higenamine is the major component underlying the fat-loss effects seen with Nelumbo Nucifera in mice studies, but human studies are non-existent at this point in time. For that reason, it’s tough to determine its degree of efficacy as a fat-burner, though the mechanisms certainly exist. Since Diablo contains several other stimulants with similar mechanisms of action, the dose of Higenamine, while not likely very high, may still be practical.
Alchemilla vulgaris, also known as Lady’s Mantle, is an herb with a somewhat limited history of use as an herbal supplement, mostly for treating stomach related issues and symptoms of menopause. It is alleged to regulate digestive enzymes, and ANS further alleges that it increases body temperature and reduces appetite. To be fair, there is no reliable human evidence for these claims.
OLIVE LEAF EXTRACT (OLEA EUROPAEA):
Olive leaf extract contains two main bioactive compounds, Hydroxytyrosol and Oleuropein, which are responsible for the majority of the adrenergic effects. A 2007 study from “The Journal of Nutritional Biochemistry” demonstrated increased Noradrenaline and Adrenaline levels in rats following injection of Olive leaf extract, and this effect was primarily attributed to Oleuropein. Similar findings were noted in a 2013 study published in “The Journal of Nutritional Biochemistry” in which rats fed a diet high in Oleuropein experienced significantly increased Noradrenaline levels (measured by urine), though it’s worth mentioning that this was not accompanied by the usual decrease in weight. In fact, Oleuropein may actually down-regulate beta-adrenergic receptors, as evidenced in a 2012 study from “The American Journal of Clinical Nutrition” (although this was in Endothelial cells, not fat-cells).
While the weight-loss implications of Olea Europaea remain unclear, it may certainly induce the release of Noradrenaline which is generally accompanied by increased focus, mood, and perceived energy.
GRAINS OF PARADISE (AFRAMOMUM MELEGUETA):
Grains of Paradise (Aframomum melegueta) is an herb similar to Ginger and contains a few of the same bioactive compounds. Like Ginger, Grains of Paradise has some implications for increasing metabolic rate, though this has only been the subject of one human study. A 2013 study, published in the “British Journal of Nutrition”, tested the effects of Grains of Paradise extract (containing several bioactives including 6-gingerol and 6-paradol) on Brown Adipose Tissue (induced by cold exposure therapy) in healthy human subjects .
The primary function of Brown Adipose Tissue in all mammals is to turn food into heat, so it is generally activated by certain stressors such as cold exposure or calorie restriction. In this particular study, 12 of the 19 volunteers were determined to have significant Brown Adipose Tissue while 7 did not. The Brown Adipose Tissue positive subjects experienced an increase in the metabolic rate compared to the Brown Adipose Tissue negative subjects (in response to cold exposure), indicating the Grains of Paradise Extract was able to increase Metabolic Rate via activation of Brown Adipose Tissue.
Ultimately, while Grains of Paradise cannot directly activate Brown Adipose Tissue, it does appear to augment the increase in Metabolic Rate resulting from activation. This makes the extract of particular interest to those looking to lose weight through dieting, as it may very well encourage extra fat-burning during calorie restriction. It’s not clear whether Diablo contains enough Grains of Paradise to be especially effective at activating Brown Adipose Tissue.
Despite its escalating popularity in pre-workout and weight-loss supplements, Hordenine remains very under-researched. In vitro and animal studies indicate that its primary mechanism of action is via Momoamine Oxidase inhibition (similar to Tyramine) with oral doses being shown to augment Noradrenaline-induced muscle contraction while not directly inducing contractions itself. So, rather than acting as a stand-alone stimulant, Hordenine can amplify/extend the effects of other stimulants by blocking the reuptake of Noradrenaline (and other Monoamines). By blocking its reuptake, Hordenine allows more Noradrenaline to remain in the synaptic space, ultimately extending/augmenting its effects (i.e. focus, intensity, lipolysis). Unfortunately, until more human research is published we won’t know exactly how potent oral doses can be.
THE BOTTOM LINE:
From an ingredient standpoint, Diablo is incredibly well-rounded and can potentially induce weight loss via multiple mechanisms of action. While the profile is a solid one, the doses of certain key ingredients (Carnitine, Green Coffee Extract, etc.) in one serving are a little on the low side, so consuming multiple servings would be necessary to achieve clinical doses (though we would side with ANS in cautioning users not to consume more than 3 servings per day). The fact that Diablo is a powder-based supplement makes it possible to fully customize the dose, and at about 66 cents per serving, taking one or two doses to get the day started and another one several hours later is a feasible option.
- Wutzke, Klaus D., and Henrik Lorenz. “The effect of l-carnitine on fat oxidation, protein turnover, and body composition in slightly overweight subjects.”Metabolism 53.8 (2004): 1002-1006
- Seim, H., W. Kiess, and T. Richter. “Effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation in healthy adults.” Metabolism 51.11 (2002): 1389-1391.
- Melton, S. A., et al. “L-carnitine supplementation does not promote weight loss in ovariectomized rats despite endurance exercise.” International journal for vitamin and nutrition research 75.2 (2005): 156-160.
- Villani, Rudolph G., et al. “L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women.”International journal of sport nutrition and exercise metabolism 10.2 (2000): 199-207.
- Karanth, Jyothsna, and K. Jeevaratnam. “Effect of carnitine supplementation on mitochondrial enzymes in liver and skeletal muscle of rat after dietary lipid manipulation and physical activity.” (2010).
- Watanabe, Takuya, et al. “The blood pressure-lowering effect and safety of chlorogenic acid from green coffee bean extract in essential hypertension.”Clinical and experimental hypertension 28.5 (2006): 439-449.
- Thom, E. “The effect of chlorogenic acid enriched coffee on glucose absorption in healthy volunteers and its effect on body mass when used long-term in overweight and obese people.” Journal of International Medical Research 35.6 (2007): 900-908.
- Vinson, Joe A., Bryan R. Burnham, and Mysore V. Nagendran. “Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects.”Diabetes, metabolic syndrome and obesity: targets and therapy 5 (2012): 21.
- Castañer, Olga, et al. “Protection of LDL from oxidation by olive oil polyphenols is associated with a downregulation of CD40-ligand expression and its downstream products in vivo in humans.” The American journal of clinical nutrition 95.5 (2012): 1238-1244.
- Covas, María-Isabel, et al. “The Effect of Polyphenols in Olive Oil on Heart Disease Risk FactorsA Randomized Trial.” Annals of internal medicine 145.5 (2006): 333-341.
- Gimeno, Eva, et al. “Changes in the phenolic content of low density lipoprotein after olive oil consumption in men. A randomized crossover controlled trial.”British journal of nutrition 98.06 (2007): 1243-1250.
- Marrugat, Jaume, et al. “Effects of differing phenolic content in dietary olive oils on lipids and LDL oxidation.” European journal of nutrition 43.3 (2004): 140-147.
- Covas, María-Isabel, et al. “Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil phenolic compounds in humans.” Free Radical Biology and Medicine 40.4 (2006): 608-616.
- Sugita, Jun, et al. “Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men.”British Journal of Nutrition 110.04 (2013): 733-738.
- Nedergaard, Jan, Tore Bengtsson, and Barbara Cannon. “Unexpected evidence for active brown adipose tissue in adult humans.” American Journal of Physiology-Endocrinology and Metabolism 293.2 (2007): E444-E452.
- Celi, Francesco S. “Brown adipose tissue—when it pays to be inefficient.” The New England journal of medicine 360.15 (2009): 1553.
- Cannon, Barbara, and J. A. N. Nedergaard. “Brown adipose tissue: function and physiological significance.” Physiological reviews 84.1 (2004): 277-359.
- Mori, Shinobu, et al. “Enhancement of lipolytic responsiveness of adipocytes by novel plant extract in rat.” Experimental biology and medicine 234.12 (2009): 1445-1449.
- Lim, T. K. “Hemerocallis fulva.” Edible Medicinal and Non Medicinal Plants. Springer Netherlands, 2014. 822-829.
- Said, Omar, et al. “Weight Loss in Animals and Humans Treated with “Weighlevel”, a Combination of Four Medicinal Plants Used in Traditional Arabic and Islamic Medicine.” Evidence-Based Complementary and Alternative Medicine 2011 (2011).
- Barwell, C. J., et al. “Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat.” Journal of pharmacy and pharmacology41.6 (1989): 421-423.
- Nedergaard, O. A., and E. Westermann. “Action of various sympathomimetic amines on the isolated stripped vas deferens of the guinea‐pig.” British journal of pharmacology 34.3 (1968): 475-483.
- Finberg, J. P., and Ken Gillman. “Selective inhibitors of monoamine oxidase type B and the “cheese effect”.” Int Rev Neurobiol 100 (2011): 169-90.
- Nojima, Hiroshi, Mari Okazaki, and Ikuko Kimura. “Counter effects of higenamine and coryneine, components of aconite root, on acetylcholine release from motor nerve terminal in mice.” Journal of Asian natural products research 2.3 (2000): 195-203.
- Bai, Gang, et al. “Identification of higenamine in Radix Aconiti Lateralis Preparata as a beta2‐adrenergic receptor agonist1.” Acta Pharmacologica Sinica 29.10 (2008): 1187-1194.