My Cart

Close

science nutrition blog

science nutrition <strong>blog</strong>

By Robert Schinetsky

 

The weight loss industry was recently valued at $USD 212.1 billion in 2018 and it shows no signs of stopping as analysts predict it will generate approximately $USD 348.1 billion by 2025.[1]

Over $66 billion of those dollars are spent on products advertised to accelerate weight loss, of which many of those are fat burners.

And, when you consider that over 71% of adults are overweight, and 39.8% are obese, it’s obscenely easy to understand why weight loss is such big business -- we’re a nation that’s overfed and undernourished.

Despite the billions spent on weight loss products, the rise in overweight and obese individuals isn’t slowing.

Why is this?

Because the overwhelming majority of fad diets are unsustainable, and the products designed for those seeking fat loss are not developed based on good science or scientific research.

Advanced Molecular Labs has committed itself to addressing the shortcomings of the weight loss industry and helping those who want to lose weight safely and sustainably with a comprehensive and synergistic arsenal of diet and fat burning supplements all rooted in scientific research.

The AML™ Thermo Heat® Fat Burning Stack is the most complete weight loss support supplement stack on the market as it takes a multi-tiered approach to fat loss. As you’re about to see, nothing can compare to the power of the AML ThermoHeat Fat Burning Stack.

AML Ultimate Thermo Heat Fat Burning Stack

ThermoHeat capsules

The flagship product of the Advanced Molecular Labs weight loss family of products is none other than the original ThermoHeat.

Thermo Heat is built around the a key fat-loss concept that’s not included in the typical weight loss advice of “eat less, move more” -- brown fat activation.

For those of you not familiar with brown adipose tissue, it generates body heat by burning body fat via non-shivering thermogenesis. BAT is typically activated in response to cold temperature exposure in order for the body to maintain its normal body temperature.

This alternate pathway to fat loss has received immense interest in recent years, and the complimentary combination of ingredients in Thermo Heat help to maximize endogenous BAT activity, supporting greater calorie burning and faster fat loss.

Normally, BAT activity requires cold exposure, as cold stimulates the transient receptor potential vanilloid (TRPV) receptor family, which subsequently triggers the sympathetic nervous system. This leads to noradrenaline release.

Noradrenaline is a fat-burning catecholamine that binds the beta-adrenergic receptor on brown fat cells ramping up fat burning.

AML™ THERMO HEAT® sidesteps the necessity of having to stay in a walk-in freezer for any considerable amount of time by including ingredients, backed by scientific research, that stimulate the TRPV family of receptors and enact brown fat thermogenesis. This includes capsaicin (from cayenne pepper extract), ginger root extract (standardized for gingerols) and piperine from black pepper extract. For best results, you should take quick release supplements of capsaicin. Coated delayed-release, capsaicin supplements may not be as effective because they bypass the TRPV-1 receptors in the stomach and gastrointestinal track.

Not only does AML™ THERMO HEAT® contain ingredients that stimulate brown fat thermogenesis, it also includes compounds that increase the amount of brown fat in the body, namely ursolic acid.

Naturally occurring in apple peels and the Ayurveda herb Holy Basil. ursolic acid has recently been documented to increase BAT concentrations as well as the expression of UCP1 (uncoupling protein-1), which enhances thermogenesis. [4,5]

As you’re probably aware, thyroid hormone plays an important role in metabolic rate as well as thermogenesis. However, levels of thyroid hormone T3 go down when individuals follow low calorie diets. This can lead to a slowing of your metabolic rate, which decreases the amount of calories you’re burning each day and lead to weight loss plateaus.

Thermo Heat features several ingredients that support thyroid function. Chief among these is a compound naturally occurring in broccoli, tea, and grapefruit is kaempferol.

Studies have shown that the polyphenolic flavonol activates thermogenesis specifically in muscle cells sans TRPV receptor action or noradrenaline release. Rather, kaempferol ignites yet another signaling pathway in BAT by triggering thyroid hormone production.[6]

Another prominent polyphenol of note present in Thermo Heat is oleuropein.

Abundant in extra-virgin olive oil, oleuropein enhances noradrenaline secretion and increases UCP-1 in BAT.[7] And, it also supports thyroid function for a healthier metabolic rate!

Thermo Heat even includes naturally occurring bile acids which has been shown to upregulate thyroid hormone signaling and thermogenesis in brown adipose tissue.[8]

And, of course, what would a thermogenic fat burner be without some prominent energy boosters?

AML™ THERMO HEAT® contains the undisputed king of energy boosters in caffeine anhydrous.

Caffeine, as you know, is a powerful CNS stimulant. It exerts its energy-boosting properties by antagonizing the adenosine receptors in the body, but it also stimulates a powerful release of the fat-burning catecholamine dopamine.

Why is dopamine important?

Dopamine is a chemical most often associated with reward and motivation (giving us the “giddy up and go” we need to do something as well as experiencing pleasure at having accomplished our goal), but it also is involved in the regulation of brown fat thermogenesis.[33]

How so?

Dopamine, as well as its catecholamine brethren in noradrenaline (which we just discussed above) and adrenaline increase BAT thermogenesis. In fact, as little as 100mg of caffeine (about as much as a strong cup of coffee) has been shown to increase thermogenesis in humans.

Moreover, not only does caffeine prompt a strong release of dopamine into the body, but it also increases dopamine receptor availability, meaning there are more “targets” for the dopamine molecule to bind[34], creating greater energy, mood, motivation, and BAT activity.

Caffeine isn’t the only dopaminergic compound in Thermo Heat either. Each serving of this comprehensive weight loss supplement also includes p-synephrine, L-Tyrosine and Mucuna pruriens seed extract (standardized for L-dopa -- the direct precursor to dopamine).

P-synephrine is particularly noteworthy as it activates the beta-3-adrenergic receptors which are involved in brown fat activating thermogenesis.[35,36]

AML™ THERMO HEAT® combines all of these dopamine-boosting compounds in a synergistic matrix to maximize BAT activity and help the body burn more calories.

We’ve really only begun to scratch the surface of the complexities that go into making Thermo Heat one of the most comprehensive fat loss supplements on the market. For an even more indepth explanation of the intricacies of how Thermo Heat enhances brown fat thermogenesis, click here.

For added fat burning and weight loss support, stack Thermo Heat capsules during the day and Thermo Heat Nighttime before bed for round-the-clock metabolic acceleration.

AML™ Thermo Heat® Nighttime

The role of diet and exercise is pretty well understood in regard to losing weight and shedding unwanted body fat. But, there’s one pillar of successful body recomposition that is never emphasized heavily enough -- SLEEP.

Simply put, without sufficient sleep your progress in the gym, as well as that of your weight loss journey, will be severely undermined...and in more ways than one.

When we are sleep deprived, we have less energy mentally and physically -- reducing the focus and intensity with which we can train in the gym, which means you’re ultimately burning less calories during your workout.

Research has shown that when we’re sleep deprived, not only are concentrations of the “hunger hormone” ghrelin increased, but we’re also more likely to crave unhealthy foods.[9,10]

Leptin levels are also lower the day after a poor night’s sleep, which creates the ultimate no-win scenario for sticking to your diet. Not only are you hungrier than usual, you’re also craving higher calorie “junk” foods, and more likely to feel less satiated from them.

And, to top it off, insulin sensitivity is also worse following sleep deprivation and metabolic rate is decreased too.[11]

If it’s not clear by now, then we’ll state it again -- if you want to lose weight successfully, GET

ENOUGH SLEEP!

And if it’s more muscle you’re wanting to build, sleep is even more important as it is when anabolic growth hormone is released and the stress hormone cortisol is inhibited. [12]

Due to the high level of importance sleep plays in the body recomposition process, Advanced Molecular Labs created the perfect dual sleep aid/overnight thermogenic in Thermo Heat Nighttime.

Thermo Heat® Nighttime features a synergistic blend of compounds that help attack unwanted body fat by facilitating thermogenic fat loss while also promoting deeper, more restorative sleep.

Thermo Heat® Nighttime promotes better sleep through a number of research-backed compounds, including none other than melatonin.

As you probably know, melatonin is the hormone that regulates the sleep/wake cycle, and it’s production is vital to helping you fall asleep. What you might not know is that melatonin also plays an important role in energy metabolism and body weight control.

In fact, several studies note that melatonin helps the body to reduce body weight and abdominal fat without reducing calorie intake or increasing physical activity levels. Melatonin does this by increasing BAT mass and enhancing BAT activity which enhances energy expenditure and fat burning.[13,14,15,40]

Melatonin also protects against mitochondrial dysfunction and adipose tissue dysfunction via several anti-inflammatory/antioxidant actions.[41,42] As you’re likely aware, inflammation is a hallmark characteristic of obesity and type 2 diabetes.

Thermo Heat Nighttime also contains L-theanine and GABA, which helps promote feelings of relaxation, and 5-hydroxytryptophan (5-HTP).

5-HTP is an amino acid that can cross the blood-brain barrier (similar to l-theanine) where it is used to produce the neurotransmitter serotonin. Greater production of serotonin encourages feelings of tiredness and fatigue, and serotonin is also used in the production of melatonin.

Moreover, serotonin also has been noted to potentiate BAT sympathetic nerve activity and thermogenesis.[38,39]

And, the versatile neurotransmitter even plays a role in helping curb cravings and reduce appetite.[16]

However, studies have shown that plasma tryptophan levels are below normal in obese subjects, and they may also decrease when dieting, leading to increased feelings of hunger. [37]

For these reasons, Thermo Heat Nighttime includes 5-HTP to increase serotonin production, which stimulates BAT activity, helps combat feelings of hunger, boosts mood, and even promotes better sleep!

The final components of Thermo Heat Nighttime are a unique mixture of thermogenic spice compounds: capsaicin, and piperine. It also contains the thermogenic spices cinnamon bark extract and ginger root extract.

Capsaicin and piperine have been reported to stimulate TRPV1 receptors, which triggers thermogenic energy expenditure and increases calorie burning.[17,18]

Capsaicin has also feelings of satiety via increasing production of the gut-derived hormone

GLP-1, which regulates regulates food intake, subsequently leading to reductions hunger.[19]

Cinnamon (containing cinnamaldehyde) activates the TRPA1 receptor, which is a member of the TRPV1 family of receptors. Similar to the above-mentioned compounds, cinnamaldehyde also helps boost fat loss by decreasing appetite and increasing energy expenditure.[20]

Thermo Heat Fat Burning Protein

When dieting for fat loss, protein is the most important macronutrient as it helps provide the essential amino acids the body needs to preserve lean muscle mass amidst a calorie deficit and it also helps increase satiety.

Ketogenic diets have become an increasingly popular amongst individuals seeking fat loss, but due to their low protein intake, they may not be the best for retaining or building lean mass.

Thermo Heat Fat Burning Protein is an ideal protein source to use when dieting regardless of what type of diet you’re following. It contains 6.25 grams of whey protein alongside 5 grams of L-leucine, which has been shown in research to boost muscle protein synthesis as much as 25 grams of whey protein.[21]

The reason for the additional 5 grams of leucine is that it research has shown that it is the key to maximizing muscle protein synthesis. In fact some some studies indicate that taking pure leucine alone (or with a small amount of whey protein) may stimulate muscle protein synthesis to a greater degree, and thereby potentially be more anabolic than food![22]

Thermo Heat Fat Burning Protein also includes several prominent brown fat activators alongside whey protein in citrulline, folic acid, grapeskin polyphenols, MCT oil, and Paradoxine.

Citrulline is well-known in bodybuilding circles as a nitric oxide booster and performance enhancer. But, you might be interested to know it can also serve as a valuable fat burning nutrient thanks to its ability to enhance PGC-1 alpha (Peroxisome proliferator-activated receptor-gamma coactivator) in skeletal muscle.[23]

Why is this important?

Well, PGC-1 alpha increases mitochondrial biogenesis, thereby promoting muscle growth. But it also upregulate insulin-like-growth factor-1 (IGF-1) and increase fat oxidation, fat burning and thermogenesis.[24].

(Note: remember above when we mentioned that low-carb and ketogenic weight loss diets typically lead to lower levels of IGF-1, hindering the muscle building and retention process? Citrulline becomes even more important in these cases!)

As if that wasn’t reason enough to consider supplementing with citrulline, consider this -- it may also increase insulin sensitivity.

MCT (Medium chain triglycerides) have received a tremendous amount of attention lately as low-carb and ketogenic diets have gained traction in the mainstream. In case you’re not familiar with them, MCTs are a type of fat that provides fast-acting fuel for the body as it is more rapidly digested and converted to useable energy than long-chain fatty acids (LCFAs).

And, it also doesn’t require the use of the carnitine “shuttle” to carry it into the mitochondria for β-oxidation (fat burning).[25]

Additionally, MCTs also stimulate the liver to produce ketone bodies, and they can increase the release of leptin and peptide YY -- two hormones that increase satiety by promoting feelings of fullness.[26,27]

Further bolstering the brown fat activity of AML™ THERMO HEAT® Fat Burning Protein is Paradoxine, a patented grains of paradise extract standardized for 6-paradol, which has been shown in human trials to stimulate thermogenesis in brown fat and reduce body fat mass and waist circumference.[28,29]

Thermo Heat Fat Burning Protein contains the full research-backed dose of 40mg Paradoxine in every serving.

And, as we’ve mentioned with other products in the Thermo Heat family, Thermo Heat Fat Burning Protein also includes piperine (from Bioperine) to stimulate TRPV1 receptors to further bolster BAT activity, increase energy expenditure, and reduce calorie intake.

AML ThermoHeat Protein also contains a trio of notable nitric oxide-boosting compounds in LCitrulline, Grape Skin Extract, and Folic Acid.

What role could nitric oxide have in burning body fat?

Quite simply, nitric oxide has been shown to stimulate BAT activity and thermogenesis.[52,53]

Animal studies note nitric oxide inhibits proliferation and upregulates the expression of two key adipogenic marker genes in uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor (PPAR).[54,55]

PPAR-ɑ is a protein that stimulates fat breakdown in a number of different tissues in the body, including brown adipose tissue.

Furthermore, PPAR-ɑ is also activated during periods of fasting and calorie restriction (i.e.

dieting for fat loss). It comes as no surprise then that PPAR-ɑt plays a key role in ketogenesis.[56]

Other studies indicate that increased nitric oxide availability may attenuate unfavorable changes in metabolism and gene expression associated with insulin resistance.[57]

Basically, increased nitric oxide production not only helps improve performance and muscle pumps, it also supports greater BAT activity and fat burning.

AML™ THERMO HEAT® Fat Burning protein supplies a full 3 gram dose of L-Citrulline along with polyphenol-rich grape skin extract and folic acid for added NO support.

Lastly, AML™ THERMO HEAT® Fat Burning Protein contains important electrolytes in potassium and magnesium citrate. In addition to supporting hydration, these key minerals also serve as acid buffers (alkalinizers) for those who may be following a low-carb or ketogenic diet to lose weight.

In case you weren’t aware, dehydration, mineral loss, kidney stone formation, and low-level chronic acidosis are more common in individuals following low/no carb diets. What’s more, chronic acidosis can also increase muscle protein breakdown and bone loss -- something you absolutely DO NOT want to occur while dieting for fat loss as muscle is the key to retaining a high metabolic rate.

By including potassium citrate, Thermo Heat Fat Burning Protein helps reduce blood acidity, thereby preserving lean body mass. And to top it off, recent studies also suggest that potassium citrate may help prevent kidney stones in those who adopt a low-carb or ketogenic diet!

Thermo Heat Multi

The final component of the AML™ THERMO HEAT® fat burning stack is a supplement that forms the backbone of many individuals daily supplement regimen for overall health and wellness-- a multivitamin in the form of Thermo Heat Multi.

But, don’t be mistaken.

AML™ THERMO HEAT® Multi isn’t your ordinary mass-market multivitamin/multi mineral.

Some key differences between Thermo Heat Multi and the generic store brand multi you’ve probably used before is that Thermo Heat Multi contains NO calcium, iron, copper, or manganese as multiples studies[32,43,44,45,46,47,48,49] have found an association between these metals and an increased risk of:

- Cardiovascular disease

- Cancer

- Neurotoxicity

- Parkinson’s

- Alzheimer’s and other neurological diseases.

As if that wasn’t bad enough, these same minerals have also been known to generate reactive oxygen species and inflammation, which is linked to obesity![30,31]

And, researchers are also considering the use of ferritin (iron-containing protein in red blood cells) concentration as an indicator of systemic fat content and degree of insulin resistance.[44]

What’s more, supplemental calcium has also been linked to increased risk of kidney stone formation. Individuals on low-carb and ketogenic diets are already at a heightened risk of developing kidney stones, and supplementing with additional calcium may exacerbate the onset of stone formation.

Moreover, the findings of two recently studies should give consumers extra caution when considering calcium-containing dietary supplements.[50,51]

For the first study, researchers investigated the association of normal‐range serum calcium level

with arterial stiffness in 565 Korean adults participating at the Health Promotion Center of Gangnam Severance Hospital between March 2016 and May 2017.[50]

Researchers found that serum calcium levels were independently and positively associated with 10‐year CVD risk estimates. In other words, the higher the serum calcium level, the greater the risk for a cardiovascular-related event.

The most recent study, published May 7, 2019, found that calcium supplements (even at 100mg per day) was linked to a significantly increased risk of death from cancer.[51] Interestingly, the increased risk of mortality was not associated with calcium intake from food, only dietary supplements.

This is why Thermo Heat Multi contains no added calcium.

ThermoHeat Multi does supply the clinically-effective dose of Vitamin D3 at 4,000IU per serving as well as numerous thermogenic spices (many of which are found in Thermo Heat Daytime) such as capsaicin and Bioperine which support increased fat burning and help bolster the effects of the other products included in the AML™ THERMO HEAT® Fat Burning Stack.

Takeaway

Successful, sustainable weight loss is about making long-lasting changes to your current diet and exercise routine. Without these in place no supplement will make a significant impact on your weight loss aspirations.

However, when combined with proper diet, exercise, and sleep, the AML™ THERMO HEAT® Fat Burning Stack can accelerate your results, helping you feel less hungry and more satiated from your lower calorie diet while also helping you burn more body fat and retain more lean muscle in the process.

 * These statements have not been evaluated by the Food and Drug Administration. his product is not intended to diagnose, treat, cure, or prevent any disease.

References:

  1. Zion Market Research. "Global Weight Management Market Expected to Reach USD 348.1 Billion By 2025: Zion Market Research." GlobeNewswire News Room, 11 Mar.

2019, www.globenewswire.com/news-release/2019/03/11/1751411/0/en/Global-Weight-

Management-Market-Expected-to-Reach-USD-348-1-Billion-By-2025-Zion-MarketResearch.html

  1. com. "U.S. Weight Loss Market Worth $66 Billion." PR Newswire: Press Release Distribution, Targeting, Monitoring and Marketing, 20 Dec. 2017, www.prnewswire.com/news-releases/us-weight-loss-market-worth-66-billion300573968.html.
  2. "FastStats." Centers for Disease Control and Prevention, 21 Mar. 2019, cdc.gov/nchs/fastats/obesity-overweight.htm.
  3. Jager S, Trojan H, et al. Pentacyclic triterpene distribution in various plants - rich sources for a new group of multi-potent plant extracts. Molecules 2009;14, 2016-2031.
  4. Kunkel SD, Elmore CJ, et al. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. PLoS One 2012;7, e39332.
  5. da-Silva WS, Harney JW, et al. The small polyphenolic molecule kaempferol increases cellular energy expenditure and thyroid hormone activation. Diabetes 2007;56, 767-776
  6. Oi-Kano Y, Kawada T, et al. Oleuropein, a phenolic compound in extra virgin olive oil, increases uncoupling protein 1 content in brown adipose tissue and enhances noradrenaline and adrenaline secretions in rats. J Nutr Sci Vitaminol (Tokyo) 2008;54, 363-370
  7. Watanabe M, Houten SM, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006;439, 484-489
  8. Schmid, S. M., Hallschmid, M., Jauch-Chara, K., Born, J., & Schultes, B. (2008). A single night of sleep deprivation increases ghrelin levels and feelings of hunger in normalweight healthy men. Journal of Sleep Research, 17(3), 331–334. https://doi.org/10.1111/j.1365-2008.00662.x
  9. Rihm, J. S., Menz, M. M., Schultz, H., Bruder, L., Schilbach, L., Schmid, S. M., & Peters, J. (2018). Sleep deprivation selectively up-regulates an amygdala-hypothalamic circuit involved in food reward. BioRxiv, 245845. https://doi.org/10.1101/245845
  10. Sharma S, Kavuru M. Sleep and metabolism: an overview. Int J Endocrinol.

2010;2010:270832. doi:10.1155/2010/270832

  1. Van Cauter E, Spiegel K, Tasali E, Leproult R. Metabolic consequences of sleep and sleep loss. Sleep Med. 2008;9 Suppl 1(0 1):S23–S28. doi:10.1016/S13899457(08)70013-3
  2. Halpern, B., Mancini, M. C., Bueno, C., Barcelos, I. P., Edna de Melo, M., Lima, M. S., Cipolla-Neto, J. (2019). Melatonin Increases Brown Adipose Tissue Volume and Activity in Melatonin Deficient Patients: a Proof-of-Concept Study. Diabetes, db180956. https://doi.org/10.2337/db18-0956
  3. Wolden-Hanson T, Mitton DR, et al. Daily melatonin administration to middle-aged male rats suppresses body weight, intra abdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Endocrinology 2000; 141, 487-497.
  4. Tan DX, Manchester LC, et al. Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity. Obes Rev 2011; 12, 167-188.
  5. Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity, Drug Targets, 2005.
  6. Yoneshiro T and Saito M. Transient receptor potential activated brown fat thermogenesis as a target of food ingredients for obesity management. Curr Opin Clin Nutr Metab Care 2013; 16, 625-631.
  7. McNamara FN, Randall A and Gunthorpe MJ. Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). Br J Pharmacol 2005; 144, 781-790.
  8. Smeets AJ and Westerterp-Plantenga MS. The acute effects of a lunch containing capsaicin on energy and substrate utilisation, hormones, and satiety. Eur J Nutr 2009; 48, 229-234.
  9. Kim MJ, Son HJ, et al. The TRPA1 agonist, methyl syringate suppresses food intake and gastric emptying. PLoS One 2012; 8, e71603.
  10. Churchward-Venne TA, Burd NA, Mitchell CJ, et al. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol. 2012;590(11):2751-65.
  11. Yoshii, N., Sato, K., Ogasawara, R., Nishimura, Y., Shinohara, Y., & Fujita, S. (2018).

Effect of Mixed Meal and Leucine Intake on Plasma Amino Acid Concentrations in

Young Men. Nutrients . https://doi.org/10.3390/nu10101543

  1. Villareal MO, Matsukawa T, Isoda H. L-Citrulline Supplementation-Increased Skeletal

Muscle PGC-1α Expression is Associated With Exercise Performance and Increased

Skeletal Muscle Weight [published online ahead of print, 2018 Jun 25]. Mol Nutr Food Res. 2018;62(14):e1701043. doi:10.1002/mnfr.201701043

  1. Nikolić N, Rhedin M, Rustan AC, Storlien L, Thoresen GH, Strömstedt M.

Overexpression of PGC-1α increases fatty acid oxidative capacity of human skeletal muscle cells [published correction appears in Biochem Res Int. 2013;2013:347567 25. Issues, N., & Gastroenterology, I. N. (2017). The Use of Medium-Chain Triglycerides, (February).

  1. St-Onge MP, Mayrsohn B, O'Keeffe M, Kissileff HR, Choudhury AR, Laferrère B. Impact of medium and long chain triglycerides consumption on appetite and food intake in overweight men. Eur J Clin Nutr. 2014;68(10):1134-40.
  2. Cliff J. d C. Harvey, Grant M. Schofield, Micalla Williden, and Joseph A. McQuillan, “The Effect of Medium Chain Triglycerides on Time to Nutritional Ketosis and Symptoms of

Keto-Induction in Healthy Adults: A Randomised Controlled Clinical Trial,” Journal of Nutrition and Metabolism, vol. 2018, Article ID 2630565, 9 pages, 2018.

https://doi.org/10.1155/2018/2630565.

  1. Sugita, J., Yoneshiro, T., et al; “Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men; British Journal of Nutrition; (2013) 110(4), pp. 733–738
  2. Sugita J, Yoneshiro T, et al; “Daily ingestion of grains of paradise (Aframomum melegueta) extract increases whole-body energy expenditure and decreases visceral fat in humans; Journal of Nutritional Science and Vitaminology; 2014, 60(1): 22-27
  3. Cheton, P. L., & Archibald, F. S. (1988). Manganese complexes and the generation and scavenging of hydroxyl free radicals. Free Radical Biology & Medicine, 5(5–6), 325–333.
  4. Monteiro R, Azevedo I. Chronic inflammation in obesity and the metabolic syndrome. Mediators Inflamm. 2010;2010:289645. doi:10.1155/2010/289645
  5. Committee, D. W., Water, D., Isbn, C., Pdf, T., Press, N. A., Press, N. A., … Press, N. A. (2000). Copper in Drinking Water.
  6. Kohlie, R., Perwitz, N., Resch, J., Schmid, S. M., Lehnert, H., Klein, J., & Iwen, K. A. (2017). Dopamine directly increases mitochondrial mass and thermogenesis in brown adipocytes. Journal of Molecular Endocrinology, 58(2), 57–66.

https://doi.org/10.1530/JME-16-0159

  1. Volkow ND, Wang GJ, Logan J, et al. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain. Transl Psychiatry. 2015;5(4):e549. Published 2015 Apr 14. doi:10.1038/tp.2015.46
  2. Stohs SJ, Preuss HG, Shara M. A review of the receptor-binding properties of psynephrine as related to its pharmacological effects. Oxid Med Cell Longev. 2011;2011:482973. doi:10.1155/2011/482973
  3. Cypess AM, Weiner LS, Roberts-Toler C, et al. Activation of human brown adipose tissue by a β3-adrenergic receptor agonist. Cell Metab. 2015;21(1):33–38. doi:10.1016/j.cmet.2014.12.009
  4. Leif Breum, Michael H Rasmussen, Jannik Hilsted, John D Fernstrom, Twenty-four–hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction, The American Journal of Clinical

Nutrition, Volume 77, Issue 5, May 2003, Pages 1112–1118, https://doi.org/10.1093/ajcn/77.5.1112

  1. Madden, C. J., & Morrison, S. F. (2010). Endogenous activation of spinal 5hydroxytryptamine (5-HT) receptors contributes to the thermoregulatory activation of brown adipose tissue. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 298(3), R776–R783.

https://doi.org/10.1152/ajpregu.00614.2009

  1. Madden CJ, Morrison SF. Brown adipose tissue sympathetic nerve activity is potentiated by activation of 5-hydroxytryptamine (5-HT)1A/5-HT7 receptors in the rat spinal cord. 2007;54(3):487–496. doi:10.1016/j.neuropharm.2007.10.019
  2. Fernandez Vazquez, G., Reiter, R. J., & Agil, A. (2018). Melatonin increases brown adipose tissue mass and function in Zucker diabetic fatty rats: implications for obesity control. Journal of Pineal Research, 64(4), e12472. https://doi.org/10.1111/jpi.12472
  3. Karamitri, A., & Jockers, R. (2019). Melatonin in type 2 diabetes mellitus and obesity. Nature Reviews. Endocrinology, 15(2), 105–125. https://doi.org/10.1038/s41574-0180130-1
  4. Prado, N. J., Ferder, L., Manucha, W., & Diez, E. R. (2018). Anti-Inflammatory Effects of Melatonin in Obesity and Hypertension. Current Hypertension Reports, 20(5), 45. https://doi.org/10.1007/s11906-018-0842-6
  5. Chen, C., Jiang, X., Li, Y., Yu, H., Li, S., Zhang, Z., Yang, X. (2019). Low-dose oral copper treatment changes the hippocampal phosphoproteomic profile and perturbs mitochondrial function in a mouse model of Alzheimer’s disease. Free Radical Biology and Medicine, 135, 144–156.

https://doi.org/https://doi.org/10.1016/j.freeradbiomed.2019.03.002

  1. Andrews, M., Soto, N., & Arredondo-Olguin, M. (2015). Association between ferritin and hepcidin levels and inflammatory status in patients with type 2 diabetes mellitus and obesity. Nutrition (Burbank, Los Angeles County, Calif.), 31(1), 51–57.

https://doi.org/10.1016/j.nut.2014.04.019

  1. Jiang, R., Manson, J. E., Meigs, J. B., Ma, J., Rifai, N., & Hu, F. B. (2004). Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA, 291(6),

711–717. https://doi.org/10.1001/jama.291.6.711

  1. Brewer GJ. Alzheimer's disease causation by copper toxicity and treatment with zinc. Front Aging Neurosci. 2014;6:92. Published 2014 May 16. doi:10.3389/fnagi.2014.00092
  2. MacDonald, G., Nalvarte, I., Smirnova, T., Vecchi, M., Aceto, N., Dolemeyer, A., Hynes, N. E. (2014). Memo is a copper-dependent redox protein with an essential role in migration and metastasis. Science Signaling, 7(329), ra56.

https://doi.org/10.1126/scisignal.2004870

  1. Sidoryk-Wegrzynowicz M, Aschner M. Manganese toxicity in the central nervous system: the glutamine/glutamate-γ-aminobutyric acid cycle. J Intern Med. 2013;273(5):466–477. doi:10.1111/joim.12040
  2. Jimenez-Jimenez, F. J., Molina, J. A., Aguilar, M. V, Meseguer, I., Mateos-Vega, C. J., Gonzalez-Munoz, M. J., Martinez-Para, M. C. (1998). Cerebrospinal fluid levels of transition metals in patients with Parkinson’s disease. Journal of Neural Transmission

(Vienna, Austria : 1996), 105(4–5), 497–505. https://doi.org/10.1007/s007020050073

  1. Park, B, Lee, Y‐ Borderline high serum calcium levels are associated with arterial stiffness and 10‐year cardiovascular disease risk determined by Framingham risk score. J Clin Hypertens. 2019; 21: 668– 673. https://doi.org/10.1111/jch.13532
  2. Chen F, Du M, Blumberg JB, Ho Chui KK, Ruan M, Rogers G, et al. Association Among

Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S. Adults: A Cohort

Study. Ann Intern Med. 2019;170:604–613. doi: 10.7326/M18-2478

  1. Jobgen W, Meininger CJ, Jobgen SC, et al. Dietary L-arginine supplementation reduces white fat gain and enhances skeletal muscle and brown fat masses in diet-induced obese rats. J Nutr. 2009;139(2):230-7.
  2. Joffin, N. , Jaubert, A. , Durant, S. , Bastin, J. , De Bandt, J. , Cynober, L. , Moinard, C., Coumoul, X. , Forest, C. and Noirez, P. (2014), Citrulline reduces glyceroneogenesis and induces fatty acid release in visceral adipose tissue from overweight rats. Nutr. Food Res., 58: 2320-2330. doi:10.1002/mnfr.201400507
  3. Nisoli, E., & Carruba, M. O. (2006). Nitric oxide and mitochondrial biogenesis. Journal of Cell Science, 119(14), 2855 LP-2862. https://doi.org/10.1242/jcs.03062
  4. Engeli, S., Janke, J., Gorzelniak, K., Böhnke, J., Ghose, N., Lindschau, C., Sharma, A. M. (2004). Regulation of the nitric oxide system in human adipose tissue Increased eNOS, 45. https://doi.org/10.1194/jlr.M300322-JLR200
  5. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest. 1999;103(11):1489-98.
  6. Razny, U., Kiec-Wilk, B., Wator, L., Polus, A., Dyduch, G., Solnica, B., Dembinska-Kiec, A. (2011). Increased nitric oxide availability attenuates high fat diet metabolic alterations and gene expression associated with insulin resistance. Cardiovascular Diabetology, 10(1), 68. https://doi.org/10.1186/1475-2840-10-68