By Robert A. Schinetsky 

Weight loss aids (a.k.a. fat burners) are some of the most popular supplements on the market. One need only look at the aisles and aisles of weight loss supplements and franken-foods for proof that the weight loss is a big, big business.

And, when you consider the fact that roughly 40% of the population is on a weight loss diet at any given time, it’s easy to understand why fat burners are such hot commodities…but are fat burners safe?

But, amongst all of the options available from which to choose, how do you know the one you’re purchasing will actually help you lose weight and burn fat?

...or if the fat burner ingredients contained in the product are even safe to consume?

That’s where this guide comes in.

We’ve assembled a list of ingredients you should avoid next time you’re in the market for some weight loss support as well as the ingredients you should be looking for in your fat burning supplement

So, without further adieu, let’s get to it!

Worst Fat Burner Ingredients

Conjugated Linoleic Acid (CLA)

Conjugated linoleic acid burst onto the scene several years ago as a “breakthrough” stimulant-free fat loss supplement. (How many times have you heard that before?!)

Naturally occuring in beef and dairy, CLA is typically recognized as a “good” fat. It’s a polyunsaturated fatty acid that’s similar to an omega-6 fatty acid and can be found throughout the body.

Some research has documented that CLA may indeed help people lose body fat.[1,2]. However, there’s been just as many trials that have demonstrated CLA is not more effective than placebo, and it other cases, supplementing with CLA actually led to weight gain![3,4]

But, weight gains isn’t even the worst of potential drawbacks of CLA supplementation...not by a long shot.

In fact, CLA happens to have a rather “dark side.”

Two different meta analyses, both published in 2017, noted that supplementation with CLA increased inflammatory markers, including c-reactive protein (CRP) and tumor necrosis factor-α (TNF-α).[5,6]

This is particularly unsettling when you consider the fact that chronic, systemic inflammation is an key factor in a wide array of diseases including:

- Diabetes

- Heart Disease

- Metabolic syndrome

- Rheumatoid arthritis

- Alzheimer’s

- Parkinson’s

- Irritable Bowel Syndrome

- Lupus

- Chronic Obstructive Pulmonary Disorder (COPD)

- And several others

Additional research also suggests that consuming large doses of CLA supplements can lead to fat buildup in the liver, which is an indicator of diabetes and metabolic syndrome.[7,8]

CLA also has been documented to lead to other less severe side effects including:

- Nausea

- Diarrhea

- Stomach pain

- Flatulence (just what you’ve always wanted from your fat burner…)[9]

And as if the previous laundry list of drawbacks wasn’t enough reason to avoid CLA supplements, here’s another -- CLA may cause insulin resistance and decrease HDL ("good") cholesterol.[10,11]

Higenamine

Higenamine is a popular beta-adrenergic receptor agonist commonly included in over-the-counter weight loss supplements.

What is a beta-receptor agonist?

Well, fat cells have both alpha and beta receptors. The physiology is a bit complex, but essentially activation of alpha-receptors hinders fat burning and beta-receptors support fat burning. When beta-receptors are activated, the adipocyte is “unlocked” and stored fatty acids are released into the bloodstream to be oxidized for energy.

In the aftermath of the ephedrine alkaloid ban of 2004, higenamine surfaced as a possible replacement due to the fact that early animal studies noted it activated beta-receptors.

However, subsequent research has noted that higenamine is poorly absorbed in the body and has an incredibly short half-life.[37,38]

Additionally, there have been no studies investigated the safety or efficacy of higenamine in isolation regarding lipolysis or fat oxidation. And, most recently, a report by Dr. Pieter Cohen found that weight loss supplements using higenamine rarely included the actual amount listed on the supplement facts panel. Some products contained several times more than the amount listed while others contained virtually none at all.[39]

Suffice it to say there is a paucity of human data regarding the safety and efficacy of orally dosed higenamine, and as such, consumers should proceed with caution regarding this ingredient.

Ephedra Nevadensis / Viridis

Yes, this is the same plant from which ephedrine is derived.

As most of you know, ephedrine was and continues to be one of the most popular (and effective) weight loss supplements of all time.

In fact, research shows it significantly increases fat burning, and when paired with caffeine (a la the “EC stack”) it accelerate weight loss that much more.[23,24,25] Stacking caffeine and ephedrine has been documented to boost metabolic rate roughly 5%, which could lead to approximately ⅓ of a pound of extra fat loss per week.

But, the problem with ephedrine is that it’s safety buffer is rather low, meaning it’s really easy to exceed the safe dose. And, as you also probably know, ephedrine was banned (and remains as such) after several people took too much and seriously injured themselves.

While ephedrine is banned for sale in supplements, that hasn’t stopped companies from capitalizing on the popularity of the compound by including an extract of the ephedra viridis plant, sans the ephedrine alkaloids.

While research has noted that early settlers used to brew a tea from the leaves of the ephedra viridis plant, no studies have been conducted on safety or effectiveness of the extracts in humans.[26] Regarding animal studies, numerous ones indicate that the plants are toxic to sheep and cattle.

Aside from being a tasty diversion for Mormon settlers, the plant was believed to possess medicinal properties. And, Ephedra viridis was commonly used (at the time) to cure headaches, colds, fevers, headaches, and bowel disorders. It was even used in the treatment of certain sexually transmitted diseases (STDs) such as syphilis.

But alas, since its heyday as a illness-fighting brew, ephedra viridis has had virtually no research in humans regarding weight loss.

The bottom line on ephedra viridis is that without the ephedrine alkaloids it’s essentially a type of tea extract, which may or may not work. At least with green tea extract we know what we’re getting ourselves into, with ephedra viridis you’re rolling the dice, big time.

“Other” Synephrine Forms

In the aftermath of the ephedrine in supplements ban, supplement formulators began scavenging for ingredients that mimicked the effects of the powerful fat loss supplement, yet was much safer.

The result of their scouring was a compound known as synephrine.

Now, here’s where things get tricky.

Synephrine actually has three different isoforms:

- P-synephrine -- the major alkaloid of Citrus Aurantium, and the compound most often included in thermogenic weight loss supplements

- M-synephrine -- also known as phenylephrine, and

- ortho-synephrine (o-synephrine)

Research is pretty clear on p-synephrine -- it’s extremely safe and effective. It’s also one of the few “proven” commodities in terms of significant fat loss, which makes it one of the ingredients included in our list of the best supplements for fat loss (which we’ll cover down below) 

Now, as for m-synephrine...

It, along with its cousin ephedrine have a higher binding affinity for α-1 and α-2 as well as β-1 and β-2 adrenoreceptors.[27] Additionally, both ephedrine and m-synephrine readily cross the blood-brain barrier (something p-synephrine cannot easily do), leading to increased CNS and cardiovascular stimulation.

Basically, both ephedrine and m-synephrine supplementation result in increased blood pressure, heart contractility, and heart rate, while p-synephrine has virtually no impact on cardiovascular parameters, which is a good thing.[27,28]

While p-synephrine lacks the stimulatory “punch” of ephedrine and m-synephrine, it’s significantly safer for the average person, and has been documented multiple times to increase metabolic rate, lipolysis, and potentially reduce food intake.[27]

Now, in regards to isopropylnorsynephrine, which also can be found under the names isopropyloctopamine or betaphrine, while it has been found to be a stronger lipolytic agent than p-synephrine, is NOT detected in sufficient quantities in Citrus Aurantium.[30,31] Furthermore, there have been no studies to date conducted in regards to the stimulatory potential of this compound or its safety.

This means isopropylnorsynephrine does not meet the definition of a dietary supplement and should not be used in any over-the-counter thermogenics, diet pills, or fat burners.

Green Tea Extract

Green tea is one of the most widely consumed beverages on the planet, and it’s also considered one of the healthiest beverages due to the large amount of antioxidants and polyphenols it contains, particularly the catechin EGCG.

Green tea extract is also a staple inclusion in many of the best-selling weight loss supplements on the market, and for good reason. There’s a fair amount of evidence to indicate the green tea extract may enhance fat burning and weight loss.[19,20,21]

It should be noted that the results aren’t always favorable with green tea, as some trials show no fat burning effects or reduced effectiveness when individuals are habitual caffeine users.[22]

And, let’s face it, the vast majority of people (especially those that workout regularly) habitually consume caffeine.

But, there’s also a pretty alarming potential side effect from mega-dosing green tea extract -- liver damage!

A growing number of case-reports have linked green tea extract-based supplements to incidents of hepatotoxicity.[32] Numerous animal studies also support the hepatotoxic potential of high dose green tea extract and EGCG supplements.[33,34,35]

How is it that something that’s generally considered healthy can also possibly be hepatotoxic. 

As the saying goes, “the dose makes the poison.”

EGCG is the most prominent and potent of the polyphenols in green tea. It acts as an antioxidant when consumed in low concentrations (such as when drinking a cup of tea), but may become toxic when concentrated and mega-dosed (as is the case when included in a fat burner).

In these instances, EGCG transforms from an antioxidant into a pro-oxidant, which can lead to cell injury and death.

And, just in case you were thinking of popping some acetaminophen (tylenol), don’t even think about it. Studies note that when EGCG is taken alongside the popular pain killer, it may potentiate the liver-damaging effects of acetaminophen.[36]

Recently, Canada has introduced new measures to toughen warnings regarding green tea extracts amidst the growing concern about liver injury.

L-Carnitine

L-carnitine is an important compound for energy production, more specifically burning fat for fuel.

You see, on their own, fatty acids cannot enter the mitochondria (the mini “nuclear reactor”) of the cell to be oxidized (“burned”) for energy. They need a carrier or “shuttle” to transport them into the mitochondria. L-carnitine is the “taxi” for fatty acids.

In theory, by supplementing with L-carnitine, an individual would increase their carnitine stores, and thus, increase the rate at which they burn fat for fuel.

However, this theory hasn’t exactly held up in science, and on more than one front, too.

First, free form l-carnitine is poorly absorbed on its own, and the research trials indicating its ability to increase body carnitine stores had subjects consume a heaping helping of carbohydrates (as much as 80 grams in some studies!).[12]

Let’s not forget that when dieting, carbs are usually restricted and is it really worth blowing 80 grams of your daily carb allotment to get a marginal increase in carnitine stores? Not really.

And don’t forget that carbs increase insulin, and increases in insulin promote nutrient storage (including fat storage) as well as hinder fat burning.

But that’s not the worst of it, even in the cases where carnitine was documented to increase muscle carnitine stores, it didn’t actually lead to any additional weight loss.[13] This is the real “nail in the coffin” against the theory that supplementing with carnitine helps burn body fat and enhance weight loss.

Additionally, athletes supplementing with L-carnitine to improve exercise performance may want to re-think their use of the compound as two recent studies have concluded that supplementing with L-Carnitine has no significant effect on performance.[15,16]

Finally, there may be some very real health concerns in regards to L-Carnitine as evidenced by recent studies noting an association between carnitine intake levels and increases in levels of a compound known as TMAO (trimethylamine N-oxide).

Why is this a problem?

Basically, when you ingest certain nutrients, such as choline or L-carnitine (both abundant in meat and energy drinks), your gut bacteria break them down and produce trimethylamine (TMA). The liver subsequently converts TMA into TMAO, which isn’t all that great for your heart.

Recent research has pretty strongly shown that high levels of TAMO increase risk for clot-related events, including stroke and heart attack and stroke.[17]

Most recently an analysis involving 2200+ pateints with coronary artery disease, researchers showed that high blood levels of TMAO were associated with higher rates of premature death.[18] In fact, the individuals with higher TMAO levels had a four-fold greater risk of dying from any cause over the next five years.

Exogenous Ketones (BHB Salts)

With the surge in popularity in low carb and ketogenic diets the past few years, exogenous ketones, such as BHB salts and ketone esters, have become immensely popular in pre workouts, fat burners, and intra workouts designed for ketogenic athletes.

Exogenous ketones are marketed to help “ease” the transition to ketosis, reduce symptoms of “keto flu”, and “teach” the body how to burn fat for fuel. BHB salts in particular provide the body with a readily accessible fuel source, while you starve your body of glucose and hasten the transition to running on ketone bodies.

However, there is a considerable lack of research regarding exogenous ketone salts and esters demonstrating that supplementation eases the transition to ketosis or reduces symptoms of “keto flu” (i.e. brain fog, lethargy, muscle cramps, headaches, constipation)[7]

In regards to burning stored body fat and subsequently inducing weight loss, BHB salts should be on the very bottom of your list of supplements.

Why is that?

When you supplement with BHB salts, you are supplying your cells with ketone bodies. As a result, your body’s downregulates endogenous production of ketones, meaning you’re reducing your body’s ability to run on stored fat. After it finishes burning the exogenous ketones for energy, it will resume ketone generation from body fat stores.

Additionally, your body has feedback mechanisms that reduce ketone production if ketone levels get too high. So, if you’re chugging BHB salts all day long, your body will drops its own ketone production to prevent your blood from getting too acidic.[41,42,43]

There’s more though.

Ketone supplements (BHB salts) can increase insulin secretion, which inhibits lipolysis (and fat burning).

This would also hold true for a glucose-field individual. If they are consuming carb-containing foods all day long, insulin levels and blood sugar would increase, limiting fat burning and promoting fat storage for any energy that was not immediately used.

Taking all of this into account, it’s hard to see how ketone supplements support or enhance fat loss.

3 Best Fat Loss Supplements Backed by Research

Caffeine

Caffeine is far and away the most popular and well-researched fat loss stimulant on the market. There’s no wonder it’s found in most fat burning supplements.

Caffeine’s main mode of action is the the inhibition or “blocking” of adenosine receptors. In doing so, caffeine promotes wakefulness and alertness.[44] But that’s not all caffeine does.

It also increases dopamine production of the body as well as adrenaline -- a very important fat burning catecholamine.[45] Specifically, adrenaline can causes an increase in metabolic rate.[46]

Caffeine also supports weight loss in a number of other ways, too. Research studies indicate that caffeine may[47,48,49]:

- Increase energy expenditure

- Reduce appetite

- Stimulate lipolysis

- Enhance the effects of other fat burning supplements

- Improve exercise performance (which helps you burn more calories during training)

Caffeine has also been shown to be safe when consumed at reasonable levels.

Synephrine

We discussed p-Synephrine up top when discussing the “other” synephrine forms on the market, but as a quick recap:

p‐Synephrine is a naturally-occurring phenylethylamine derivative similar in structure to ephedrine that is found in bitter orange (Citrus aurantium). It can also be produced in your body using the same pathways involved in the production of catecholamines (such as adrenaline and noradrenaline).

Unlike ephedrine and m-synephrine, p-synephrine has a very low binding affinity for alpha-receptors as well as β-1 and β-2 adrenoreceptors. However, it does bind to β-3 adrenoreceptors, leading to:

- increased metabolic rate

- Enhanced lipolysis

- Increased fat oxidation during exercise

- reduced food intake

p-synephrine has also been noted to confer performance-boosting benefits.

Regarding safety, research has shown that doses up to 3 mg/kg are well tolerated and subject do not experience any adverse side effects. And, when combined with caffeine, p-synephrine actually gets more effective!

ThermoHeat -- A Real Fat Burner Built on Science!

ThermoHeat is a scientifically-formulated weight loss supplement built on a foundation of proven fat burner ingredients that enhance metabolism, boost fat burning, improve mood, reduce cravings, and activate dormant white adipose tissue (WAT) so that it acts more similar to the calorie-burning brown adipose tissue (BAT) or brown fat.

So are fat burners safe? As we have discussed, not all of them are. However, ThermoHeat is unlike any other fat burner on the market for the simple reason that it doesn’t rely on a collection of harsh stimulants or ingredients backed by pseudoscience.

Try ThermoHeat for yourself and see what an authentic fat burner is all about.

References

1. Watras AC , et al. "The Role of Conjugated Linoleic Acid in Reducing Body Fat and Preventing Holiday Weight Gain. - PubMed - NCBI." National Center for Biotechnology Information,.
2. Chen SC , et al. "Effect of Conjugated Linoleic Acid Supplementation on Weight Loss and Body Fat Composition in a Chinese Population. - PubMed - NCBI." National Center for Biotechnology Information.
3. Joseph SV , et al. "Conjugated Linoleic Acid Supplementation for 8 Weeks Does Not Affect Body Composition, Lipid Profile, or Safety Biomarkers in Overweight, Hyperlipi... - PubMed - NCBI." National Center for Biotechnology Information.
4. Risérus U , et al. "Effects of Cis-9,trans-11 Conjugated Linoleic Acid Supplementation on Insulin Sensitivity, Lipid Peroxidation, and Proinflammatory Markers in Obese... - PubMed - NCBI." National Center for Biotechnology Information,.
5. Mazidi M, Karimi E, Rezaie P, Ferns GA. Effects of conjugated linoleic acid supplementation on serum C-reactive protein: A systematic review and meta-analysis of randomized controlled trials. Cardiovasc Ther. 2017;35(6). doi:10.1111/1755-5922.12275
6. Haghighatdoost F, Nobakht M Gh BF. Effect of conjugated linoleic acid on blood inflammatory markers: a systematic review and meta-analysis on randomized controlled trials. Eur J Clin Nutr. December 2017. doi:10.1038/s41430-017-0048-z
7. Diwakar Vyas, Anil Kumar G. Kadegowda, and Richard A. Erdman, “Dietary Conjugated Linoleic Acid and Hepatic Steatosis: Species-Specific Effects on Liver and Adipose Lipid Metabolism and Gene Expression,” Journal of Nutrition and Metabolism, vol. 2012, Article ID 932928, 13 pages, 2012. https://doi.org/10.1155/2012/932928.
8. Clement L, Poirier H, Niot I, et al. Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. J Lipid Res. 2002;43(9):1400-1409
9. Gaullier J-M, Halse J, Hoye K, et al. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am J Clin Nutr. 2004;79(6):1118-1125. doi:10.1093/ajcn/79.6.1118
10. Risérus U, Arner P, Brismar K, Vessby B. Treatment With Dietary trans10cis12 Conjugated Linoleic Acid Causes Isomer-Specific Insulin Resistance in Obese Men With the Metabolic Syndrome. Diabetes Care. 2002;25(9):1516 LP-1521..
11. Risérus U, Basu S, Jovinge S, Fredrikson GN, Ärnlöv J, Vessby B. Supplementation With Conjugated Linoleic Acid Causes Isomer-Dependent Oxidative Stress and Elevated C-Reactive Protein. Circulation. 2002;106(15):1925 LP-1929.
12. Wall BT, Stephens FB, et al. Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in human J Physiol 2011; 589, 963-973.
13. Villani RG , et al. "L-Carnitine Supplementation Combined with Aerobic Training Does Not Promote Weight Loss in Moderately Obese Women. - PubMed - NCBI." National Center for Biotechnology Information, ncbi.nlm.nih.gov/pubmed/10861338.
14. Sahlin K. Boosting fat burning with carnitine: an old friend comes out from the shadow. J Physiol. 2011;589(Pt 7):1509-10.
15. P Peeling, MJ Binnie, et al. Evidence-Based Supplements for the Enhancement of Athletic Performance. International Journal of Sport Nutrition and Exercise Metabolism, 28; 2. 3/2018 (28) 178-187.
16. Christopher E. Shannon, et al. Increasing skeletal muscle carnitine availability does not alter the adaptations to high-intensity interval training. Scand J Med Sci Sports. 2018;28: 107-115.
17. Zhu W , et al. "Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. - PubMed - NCBI." National Center for Biotechnology Information,.
18. "Intestinal Microbiota'Generated Metabolite Trimethylamine'N'Oxide and 5'Year Mortality Risk in Stable Coronary Artery Disease: The Contributory Role of Intestinal Microbiota in a COURAGE'Like Patient Cohort." PubMed Central (PMC),.
19. Nagao T, et al. Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men. Am J Clin Nutr. (2005)
20. Wang H, et al. Effects of catechin enriched green tea on body composition. Obesity (Silver Spring). (2010)
21. Maki KC, et al. Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. J Nutr. (2009)
22. Westerterp-Plantenga MS, Lejeune MP, Kovacs EM. Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation. Obes Res. (2005)
23. Bogacka I , et al. "The Effect of Beta-adrenergic and Peroxisome Proliferator-activated Receptor-gamma Stimulation on Target Genes Related to Lipid Metabolism in Human... - PubMed - NCBI." National Center for Biotechnology Information, ncbi.nlm.nih.gov/pubmed/17351280.
24. Diepvens K , et al. "Obesity and Thermogenesis Related to the Consumption of Caffeine, Ephedrine, Capsaicin, and Green Tea. - PubMed - NCBI." National Center for Biotechnology Information.
25. D, Molnár. "Effects of Ephedrine and Aminophylline on Resting Energy Expenditure in Obese Adolescents. - PubMed - NCBI." National Center for Biotechnology Information.
26. Keeler F. Richard. (1989). Investigation of maternal and embryo/fetal toxicity of Ephedra viridis and\n Ephedra nevadensis in sheep and cattle. J. Range Manage., 42(1), 31–35. https://doi.org/10.2307/3899654
27. Stohs SJ, Preuss HG, Shara M. A review of the receptor-binding properties of p-synephrine as related to its pharmacological effects. Oxid Med Cell Longev. 2011;2011:482973.
28. Shara M , et al. "Cardiovascular Safety of Oral P-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial. - PubMed - NCBI." National Center for Biotechnology Information.
29. Stohs SJ. Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine. Phytother Res. 2017;31(10):1463-1474.
30. Roman MC, Betz JM, Hildreth J. Determination of synephrine in bitter orange raw materials, extracts, and dietary supplements by liquid chromatography with ultraviolet detection: single-laboratory validation. J AOAC Int. 2007;90(1):68-81.
31. Mercader J , et al. "Isopropylnorsynephrine is a Stronger Lipolytic Agent in Human Adipocytes Than Synephrine and Other Amines Present in Citrus Aurantium. - PubMed - NCBI." National Center for Biotechnology Information.
32. James KD , et al. "Potential Role of the Mitochondria As a Target for the Hepatotoxic Effects of (-)-epigallocatechin-3-gallate in Mice. - PubMed - NCBI." National Center for Biotechnology Information.
33. Lambert JD , et al. "Hepatotoxicity of High Oral Dose (-)-epigallocatechin-3-gallate in Mice. - PubMed - NCBI." National Center for Biotechnology Information,.
34. Weng Z , et al. "Green Tea Epigallocatechin Gallate Binds to and Inhibits Respiratory Complexes in Swelling but Not Normal Rat Hepatic Mitochondria. - PubMed - NCBI." National Center for Biotechnology Information, ncbi.nlm.nih.gov/pubmed/24384371.
35. "Sensitivity to Hepatotoxicity Due to Epigallocatechin Gallate is Affected by Genetic Background in Diversity Outbred Mice." ScienceDirect.com | Science, Health and Medical Journals, Full Text Articles and Books, sciencedirect.com/science/article/pii/S0278691514004669.
36. Salminen WF , et al. "Green Tea Extract Can Potentiate Acetaminophen-induced Hepatotoxicity in Mice. - PubMed - NCBI." National Center for Biotechnology Information, ncbi.nlm.nih.gov/pubmed/22306919.
37. Lo, C.F., Chen, C.M., 1996. Pharmacokinetics of higenamine in rabbits. Biopharm. Drug Dispos. 17 (9), 791–803.
38. Feng S, Jiang J, Hu P, et al. A phase I study on pharmacokinetics and pharmacodynamics of higenamine in healthy Chinese subjects. Acta Pharmacologica Sinica. 2012;33(11):1353-1358. doi:10.1038/aps.2012.114.
39. Pieter A. Cohen, John C. Travis, Peter H. J. Keizers, Frederick E. Boyer & Bastiaan J. Venhuis (2018) The stimulant higenamine in weight loss and sports supplements, Clinical Toxicology, DOI: 10.1080/15563650.2018.1497171
40. Harvey CJDC, Schofield GM, Williden M. The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review. PeerJ. 2018;6:e4488. Published 2018 Mar 16. doi:10.7717/peerj.4488
41. Leckey JJ, Ross ML, Quod M, Hawley JA, Burke LM. Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists. Front Physiol. 2017;8:806. Published 2017 Oct 23. doi:10.3389/fphys.2017.00806
42. Evans M, Cogan KE, Egan B. Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation. J Physiol. 2016;595(9):2857-2871.
43. Taggart, A. K. P., Kero, J., Gan, X., Cai, T.-Q., Cheng, K., Ippolito, M., Waters, M. G. (2005). (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. The Journal of Biological Chemistry, 280(29), 26649–26652. https://doi.org/10.1074/jbc.C500213200
44. Ferre S , et al. "Adenosine A1-A2A Receptor Heteromers: New Targets for Caffeine in the Brain. - PubMed - NCBI." National Center for Biotechnology Information.
45. Graham TE and Spriet LL. "Metabolic, Catecholamine, and Exercise Performance Responses to Various Doses of Caffeine. - PubMed - NCBI." National Center for Biotechnology Information.
46. Acheson KJ , et al. "Caffeine and Coffee: Their Influence on Metabolic Rate and Substrate Utilization in Normal Weight and Obese Individuals. - PubMed - NCBI." National Center for Biotechnology Information, ncbi.nlm.nih.gov/pubmed/7369170.
47. "Metabolic Effects of Caffeine in Humans: Lipid Oxidation or Futile Cycling?" OUP Academic, 1 Jan. 2004.
48. Caffeine reduces spontaneous energy intake in men but not in women

• Pasman WJ , et al. "The Effect of Different Dosages of Caffeine on Endurance Performance Time. - PubMed - NCBI." National Center for Biotechnology Information.