It seems like there's been a lot of discussion lately about caffeine/stimulant intake, breaks, tolerance, effects, etc, so I figured this would be a good time to post up this guide/article on the benefits of caffeine and the doses needed/used to provide these effects in studies.
I know most of this may not be anything new or exciting for a lot of people here, but I still think it can be a good resource for people to look at to help them decide how much caffeine they want to take for a given purpose, and what to stack with it. With that said, here we go:
Caffeine
Caffeine is the most commonly used central nervous system (CNS) stimulant known to man. This plant alkaloid has a half-life of approximately 5 hours in healthy individuals, and reaches peak plasma concentration between 15-120 minutes after oral ingestion, with the variation among individuals in half-life and peak concentration depending on a variety of factors including smoking, altitude, obesity, and diet. Caffeine can be found in a variety of beverages and foods, including coffee, tea, soda, and chocolate. The focus of this article is to highlight the various benefits of caffeine supplementation, as well as the ideal doses for these benefits, as supported by published research and studies. This article will also touch on what to stack, or combine, with caffeine to potentiate its effects, helping you get the most out of humanity’s favorite plant alkaloid [1].
Cognitive Enhancement: Improving Energy, Focus, Alertness, Reaction Time, Mood, Etc.
Dosing Overview: 50-300mg
One of the most common uses of caffeine is to promote wakefulness and provide energy and focus. A wide variety of individuals can benefit from caffeine, ranging from students to businesspeople and even elite military forces. Doses as low as 50mg have been shown to improve subjective alertness and accuracy on an attention switching task [2], and 75mg has been shown to improve reaction time [3]. These doses are quite small, as a cup of brewed coffee may contain 107-151mg caffeine [4]. Somewhat higher doses of 150mg and 160mg have been found to improve reaction time, perceptions of fatigue, and rapid visual information processing [5-6]. Slightly higher doses of caffeine, 200-300mg, have also been demonstrated in numerous studies to benefits soldiers and military personnel, including reducing tiredness and cold discomfort during low temperature shooting [7], reducing errors and improving speed of target detection without negatively impacting marksmanship [8], improving reaction time, visual vigilance, repeated acquisition, and improved mood and alertness without negatively impacting marksmanship following 72 hours of sleep deprivation [9], and improved sighting time without negatively impacting accuracy [10]. Looking at these studies, it is clear that caffeine consumption can improve energy, focus, alertness, and reaction time without negatively impacting accuracy and performance, which is important, as increased speed is worthless if it comes at the cost of accuracy and precision.
Sports Performance: Endurance, Power Output, Speed
Dosing Overview: 200-400mg
Another popular use of caffeine, especially among athletes and the fitness community, is improving exercise and sports performance. Slightly higher doses of caffeine appear to be required for these benefits compared to the lower minimum doses needed to improve various aspects of cognition and mood, but that doesn’t mean massive doses of caffeine are required here. As a general rule of thumb, 3-6mg/kg is the recommended dose to improve exercise performance, which equates to about 200-400mg for a 150lb (68kg) individual. 240mg caffeine has been shown to reduce fatigue during high-intensity sprint exercise [11]. Elsewhere, 3mg/kg (about 200mg; see above) has been shown to improve power output, where 1mg/kg (about 70mg) did not [12]. Similarly, 5mg/kg (about 340mg) improved performance on knee extension and flexion, where 2mg/kg (about 140mg) did not [13]. So while lower doses may not be effective for exercise performance, the high-end of the spectrum (6mg/kg) may not be a necessity either, as one study noted improved endurance cycling performance with 3mg/kg and 6mg/kg, but the higher dose was not significantly better than the lower dose [14]. 5mg/kg can also improve print time [15], and 6mg/kg can improve performance in elite rowers [16].
Thermogenesis, Metabolic Rate, and Energy Expenditure
Dosing Overview: 100mg +
As many of you already know, caffeine possesses thermogenic properties, and is therefore a useful supplement to assist in weight loss and improving body composition. 100mg caffeine has been shown to increase the resting metabolic rate of lean and postobese humans [17], and caffeine has been found to product dose-dependent increases in energy expenditure and thermogenic response in doses from 100-400mg [18]. What this means is that higher doses of caffeine, within reason of course, are able to improve energy expenditure by more than lower doses.
What to Take with Caffeine to Maximize Benefits
The following sections will focus on what you can add to your caffeine to provide additional benefits and maximize caffeine’s effects.
L-Theanine
Dosing Overview: 100-250mg
L-Theanine is an amino acid that is found in tea. The combination of caffeine and theanine is a classic example of synergy, where two ingredient potentiate each other, and the result is truly more than the sum of its parts. Both studies and anecdotal feedback demonstrate that adding l-theanine to caffeine is able to preserve the benefits of caffeine, but also provide a clean, calm, and focused energy. The addition of 250mg l-theanine to 150mg caffeine was able to preserve the benefits of caffeine (improved reaction time, perceptions of fatigue, and rapid visual information processing), and also further improve reaction time while reducing ratings of headaches that occurred with caffeine in isolation [19]. Lower doses of caffeine and theanine are also effective, including a combination of 100mg l-theanine and 50mg caffeine improving accuracy and speed on an attention-switching task and also reducing susceptibility to distracting information on a memory task [20], and 40mg caffeine and 97mg theanine significantly improving accuracy during task switching, as well as reducing self-reported tiredness and improving self-reported alertness [21]. In light of these studies, it can be said that adding 50-250mg theanine to your caffeine is a winning-combination. Some people prefer higher or lower ratios of caffeine to theanine, including but not limited to 1:1, 1:2, and 2:1 ratios. This is subjective really, and some testing may be necessary to find the perfect ratio for you. I personally enjoy a ratio of around 2:1, favoring caffeine (around 200-250mg caffeine with 100mg theanine for study and work purposes, with 250-300mg caffeine and 100mg theanine for pre-workout purposes).
L-Ornithine HCL
Dosing Overview: 250mg
L-Ornithine is another amino acid that is synergistic with caffeine. Research has found that the addition of 250mg L-Ornithine HCL to 100mg caffeine improved mood ratings after 8 hours by more than 100mg caffeine alone, which suggests a unique synergistic effect between caffeine on mood of healthy office workers [22]. 8 hours is quite a long time to still notice the benefits of caffeine, so adding l-ornithine to caffeine appears to be an effective way to extend the beneficial effects of caffeine and perhaps also delay or even prevent the crash some people get several hours after taking caffeine.
Choline
Dosing Overview: See Choline Guide
http://anabolicminds.com/forum/nootropics/296327-choline-supplementation-stacking.html
Interestingly, caffeine has been shown to increase choline’s ability to increase acetylcholine [23], meaning caffeine can potentiate the effects of choline, making the two an effective combination in nootropic stacks. For more information on choline, including the different choline sources, how to dose choline, the effects of choline, as well as what to stack with choline, see the Choline Guide http://anabolicminds.com/forum/nootropics/296327-choline-supplementation-stacking.html.
Carnitine
Dosing Overview: 1-2g
Caffeine may be able to improve carnitine’s benefits on exhaustion time and fat oxidation [24].
Theacrine
Dosing Overview: 50-200mg
Theacrine is a purine alkaloid derived from caffeine. Like its popular cousin caffeine, theacrine is also able to increase energy, focus, and concentration [25-26]. Additionally, doses of up to 300mg/day theacrine for 8 weeks appears not to have a tachyphylactic/habituation response, which means that it may not be subject to the same tolerance that caffeine is, where you eventually need higher doses of caffeine to feel the same effects [27]. This promising alkaloid is the perfect complement to caffeine, as it allows you to keep your caffeine dose a bit lower and avoid some tolerance from developing. Studies using theacrine alone tend to use 100-300mg, but theacrine is probably most often used in addition to caffeine to provide a boost, with doses of 50-100mg being common additions to caffeine.
Safety of Caffeine Consumption
Caffeine is likely the most often ingested pharmacologically active substance known to man. A review of published human studies concluded that moderate daily caffeine intake at a dose of up to 400mg/day (6mg/kg body weight for a 65kg human) is not associated with adverse effects including general toxicity, cardiovascular effects, effects on bones status, changes in adult behavior, or increased incidence of cancer and effects on male infertility. This review also concluded that reproductive-aged women should consume no more than 300mg/day caffeine (4.6mg/kg for a 65kg woman) [28]. With this in mind, it seems safe to say that there is really no need to go above 400mg/day caffeine for men, or 300mg/day for women, especially considering that all of the benefits of caffeine, including improving energy, focus, reaction time, cognition, and exercise performance, are all obtainable without going above these doses.
Update:
It seems a lot of people are interested in knowing what the highest amount of caffeine that is "safe/reasonable/etc" is. As mentioned earlier, the 400mg/day for men and 300mg/day for reproductive-aged women is a good "safe" amount (assuming average weight, no medical conditions, etc). With that said, a lot of people will/do go over 400mg/day, but I'd still caution you that if you do go above 400mg, which may not be the best idea for chronic (very long term) use, do not exceed 600mg/day, which is supported by the following summary from the U.S. Army's formulations for military operations:
Summary: Dosing/Stacking Guide
Caffeine
Energy, Focus, Alertness, Reaction Time: (50-300mg)
Doses as low as 50mg have shown benefits, but 200-300mg may be preferable for more physically demanding or intensive activities
Exercise Performance: Endurance, Power Output, Improved Time (200-400mg)
3-6mg/kg (~200-400mg for a 150lb person) caffeine has been shown to improve various aspects of exercise performance, with studies noting no significant improvement with 1-2mg/kg (~70-140mg for a 150b person), and one study noting no additional benefits with 6mg/kg (~400mg) compared to 3mg/kg (200mg).
Thermogenesis (100mg +)
Improved thermogenesis and metabolic rate with 100mg, and dose-dependent response up to 400mg
L-Theanine (100-250mg)
Synergistic with caffeine; further improves benefits of caffeine such as reaction time while also reducing potential side effects of caffeine (promotes a calm, focused energy)
L-Ornithine HCL (250mg)
Synergistic with caffeine; improves mood by more than caffeine alone at 8 hours, suggesting it could potentiate the effects of caffeine and the duration of these effect
Choline (see choline article)
Caffeine is able to enhance choline’s ability to release acetylcholine
Carnitine (1-2g +)
Caffeine may be able to increase carnitine’s benefits on exhaustion time and fat oxidation
Theacrine (50+mg, preferably as a “boost” to caffeine, so dose accordingly)
A purine alkaloid derived from caffeine. Possesses similar effects as caffeine, but may not be subject to the same habituation/tolerance that caffeine is
References:
1 https://www.ncbi.nlm.nih.gov/books/NBK223808/
2. http://www.ncbi.nlm.nih.gov/pubmed/18681988
3. https://www.ncbi.nlm.nih.gov/pubmed/20521321
4. https://www.ncbi.nlm.nih.gov/pubmed/762339
5. http://www.ncbi.nlm.nih.gov/pubmed/18006208
6. http://www.ncbi.nlm.nih.gov/pubmed/26869148
7. http://www.tandfonline.com/doi/pdf/10.1080/0014013032000121606
8. https://www.ntis.gov/Search/Home/titleDetail/?abbr=ADA387188
9. http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier=ADA331982
10. http://www.ncbi.nlm.nih.gov/pubmed/12688447
11. https://www.ncbi.nlm.nih.gov/pubmed/20737165
12. https://www.ncbi.nlm.nih.gov/pubmed/22569090
13. https://www.ncbi.nlm.nih.gov/pubmed/20421833
14. https://www.ncbi.nlm.nih.gov/pubmed/22142020
15. https://www.ncbi.nlm.nih.gov/pubmed/18799995
16. https://www.ncbi.nlm.nih.gov/pubmed/21799214
17. https://www.ncbi.nlm.nih.gov/pubmed/2912010
18. https://www.ncbi.nlm.nih.gov/pubmed/2333832
19. http://www.ncbi.nlm.nih.gov/pubmed/18006208
20. https://www.ncbi.nlm.nih.gov/pubmed/18681988
21. http://www.ncbi.nlm.nih.gov/pubmed/21040626
22. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287333/
23. https://www.ncbi.nlm.nih.gov/pubmed/1435067
24. https://www.ncbi.nlm.nih.gov/pubmed/11922111
25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711067/
26. https://www.ncbi.nlm.nih.gov/labs/articles/27164220/
27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271659/
28. https://www.ncbi.nlm.nih.gov/pubmed/12519715
Edit: Additions:
Ephedrine and Caffeine (EC) Stack
Commonly 200mg caffeine and 20mg ephedrine three times daily
*note: Ephedrine is not considered a "supplement" in the United States, and may not be in other areas. Be sure to obey all laws where you live. The following is purely scientific information, not advocating/condoning/etc anything.
The combination of Ephedrine and Caffeine, commonly referred to as an EC stack (or ECA when Aspirin is added, which will not be discussed here), is a common and effective stack for fat-loss. Ephedrine and caffeine are synergistic, with studies noting that while neither caffeine (200mg 3x daily) or ephedrine (20mg 3x daily) were effective for the treatment of obesity, the combination of 200mg caffeine and 20mg ephedrine 3x daily was. Additionally, side effects (tremor, insomnia and dizziness) were transient, and after 8 weeks of use they reached placebo levels [1]. EC has been shown to increase energy expenditure (fat oxidation) while also preserving lean mass (muscle) [2,4]. This combination is often used for somewhat long periods of time (studies have used EC daily for at least 24 weeks), and research suggests that "the side-effects are minor and transient and no clinically relevant withdrawal symptoms have been observed," and "the ephedrine/caffeine combination is safe and effective in long-term treatment in improving and maintaining weight loss" [3]. Additionally, "the hemodynamic and side effects to E+C are transient during chronic treatment, while the effect on energy expenditure persists. The compound also possesses repartitioning properties, which may be useful in the treatment of obesity" [5]. In healthy, lean subjects, the thermogenic effect of 20mg E and 200mg C was greater than 10 or 20mg E alone, 100 or 200mg C alone, and also greater than 10mg E + 200mg C or 20mg E and 100mg C (supra-additive synergism for the 20/200mg dose, with only additive effects at the other doses). Additionally, all three combinations of E&C resulted in a 3-hour postintake increase in systolic blood pressure of 5-7 mm Hg more than placebo. Diastolic blood pressure was not increased by 20/200mg, while the other two combinations increased it by around 4mm Hg more than placebo. Finally, 20mg E and 200mg C (and 20mg E and 100mg C) increased heartrate more than placebo, while 10mg E + 200mg C had no effect on heartrate [6].
1: https://www.ncbi.nlm.nih.gov/pubmed/1318281
2: https://www.ncbi.nlm.nih.gov/pubmed/1619985
3: https://www.ncbi.nlm.nih.gov/pubmed/8124407
4: https://www.ncbi.nlm.nih.gov/pubmed/8384186
5: https://www.ncbi.nlm.nih.gov/pubmed/8384179
6: https://www.ncbi.nlm.nih.gov/pubmed/2000046
I know most of this may not be anything new or exciting for a lot of people here, but I still think it can be a good resource for people to look at to help them decide how much caffeine they want to take for a given purpose, and what to stack with it. With that said, here we go:
Caffeine
Caffeine is the most commonly used central nervous system (CNS) stimulant known to man. This plant alkaloid has a half-life of approximately 5 hours in healthy individuals, and reaches peak plasma concentration between 15-120 minutes after oral ingestion, with the variation among individuals in half-life and peak concentration depending on a variety of factors including smoking, altitude, obesity, and diet. Caffeine can be found in a variety of beverages and foods, including coffee, tea, soda, and chocolate. The focus of this article is to highlight the various benefits of caffeine supplementation, as well as the ideal doses for these benefits, as supported by published research and studies. This article will also touch on what to stack, or combine, with caffeine to potentiate its effects, helping you get the most out of humanity’s favorite plant alkaloid [1].
Cognitive Enhancement: Improving Energy, Focus, Alertness, Reaction Time, Mood, Etc.
Dosing Overview: 50-300mg
One of the most common uses of caffeine is to promote wakefulness and provide energy and focus. A wide variety of individuals can benefit from caffeine, ranging from students to businesspeople and even elite military forces. Doses as low as 50mg have been shown to improve subjective alertness and accuracy on an attention switching task [2], and 75mg has been shown to improve reaction time [3]. These doses are quite small, as a cup of brewed coffee may contain 107-151mg caffeine [4]. Somewhat higher doses of 150mg and 160mg have been found to improve reaction time, perceptions of fatigue, and rapid visual information processing [5-6]. Slightly higher doses of caffeine, 200-300mg, have also been demonstrated in numerous studies to benefits soldiers and military personnel, including reducing tiredness and cold discomfort during low temperature shooting [7], reducing errors and improving speed of target detection without negatively impacting marksmanship [8], improving reaction time, visual vigilance, repeated acquisition, and improved mood and alertness without negatively impacting marksmanship following 72 hours of sleep deprivation [9], and improved sighting time without negatively impacting accuracy [10]. Looking at these studies, it is clear that caffeine consumption can improve energy, focus, alertness, and reaction time without negatively impacting accuracy and performance, which is important, as increased speed is worthless if it comes at the cost of accuracy and precision.
Sports Performance: Endurance, Power Output, Speed
Dosing Overview: 200-400mg
Another popular use of caffeine, especially among athletes and the fitness community, is improving exercise and sports performance. Slightly higher doses of caffeine appear to be required for these benefits compared to the lower minimum doses needed to improve various aspects of cognition and mood, but that doesn’t mean massive doses of caffeine are required here. As a general rule of thumb, 3-6mg/kg is the recommended dose to improve exercise performance, which equates to about 200-400mg for a 150lb (68kg) individual. 240mg caffeine has been shown to reduce fatigue during high-intensity sprint exercise [11]. Elsewhere, 3mg/kg (about 200mg; see above) has been shown to improve power output, where 1mg/kg (about 70mg) did not [12]. Similarly, 5mg/kg (about 340mg) improved performance on knee extension and flexion, where 2mg/kg (about 140mg) did not [13]. So while lower doses may not be effective for exercise performance, the high-end of the spectrum (6mg/kg) may not be a necessity either, as one study noted improved endurance cycling performance with 3mg/kg and 6mg/kg, but the higher dose was not significantly better than the lower dose [14]. 5mg/kg can also improve print time [15], and 6mg/kg can improve performance in elite rowers [16].
Thermogenesis, Metabolic Rate, and Energy Expenditure
Dosing Overview: 100mg +
As many of you already know, caffeine possesses thermogenic properties, and is therefore a useful supplement to assist in weight loss and improving body composition. 100mg caffeine has been shown to increase the resting metabolic rate of lean and postobese humans [17], and caffeine has been found to product dose-dependent increases in energy expenditure and thermogenic response in doses from 100-400mg [18]. What this means is that higher doses of caffeine, within reason of course, are able to improve energy expenditure by more than lower doses.
What to Take with Caffeine to Maximize Benefits
The following sections will focus on what you can add to your caffeine to provide additional benefits and maximize caffeine’s effects.
L-Theanine
Dosing Overview: 100-250mg
L-Theanine is an amino acid that is found in tea. The combination of caffeine and theanine is a classic example of synergy, where two ingredient potentiate each other, and the result is truly more than the sum of its parts. Both studies and anecdotal feedback demonstrate that adding l-theanine to caffeine is able to preserve the benefits of caffeine, but also provide a clean, calm, and focused energy. The addition of 250mg l-theanine to 150mg caffeine was able to preserve the benefits of caffeine (improved reaction time, perceptions of fatigue, and rapid visual information processing), and also further improve reaction time while reducing ratings of headaches that occurred with caffeine in isolation [19]. Lower doses of caffeine and theanine are also effective, including a combination of 100mg l-theanine and 50mg caffeine improving accuracy and speed on an attention-switching task and also reducing susceptibility to distracting information on a memory task [20], and 40mg caffeine and 97mg theanine significantly improving accuracy during task switching, as well as reducing self-reported tiredness and improving self-reported alertness [21]. In light of these studies, it can be said that adding 50-250mg theanine to your caffeine is a winning-combination. Some people prefer higher or lower ratios of caffeine to theanine, including but not limited to 1:1, 1:2, and 2:1 ratios. This is subjective really, and some testing may be necessary to find the perfect ratio for you. I personally enjoy a ratio of around 2:1, favoring caffeine (around 200-250mg caffeine with 100mg theanine for study and work purposes, with 250-300mg caffeine and 100mg theanine for pre-workout purposes).
L-Ornithine HCL
Dosing Overview: 250mg
L-Ornithine is another amino acid that is synergistic with caffeine. Research has found that the addition of 250mg L-Ornithine HCL to 100mg caffeine improved mood ratings after 8 hours by more than 100mg caffeine alone, which suggests a unique synergistic effect between caffeine on mood of healthy office workers [22]. 8 hours is quite a long time to still notice the benefits of caffeine, so adding l-ornithine to caffeine appears to be an effective way to extend the beneficial effects of caffeine and perhaps also delay or even prevent the crash some people get several hours after taking caffeine.
Choline
Dosing Overview: See Choline Guide
http://anabolicminds.com/forum/nootropics/296327-choline-supplementation-stacking.html
Interestingly, caffeine has been shown to increase choline’s ability to increase acetylcholine [23], meaning caffeine can potentiate the effects of choline, making the two an effective combination in nootropic stacks. For more information on choline, including the different choline sources, how to dose choline, the effects of choline, as well as what to stack with choline, see the Choline Guide http://anabolicminds.com/forum/nootropics/296327-choline-supplementation-stacking.html.
Carnitine
Dosing Overview: 1-2g
Caffeine may be able to improve carnitine’s benefits on exhaustion time and fat oxidation [24].
Theacrine
Dosing Overview: 50-200mg
Theacrine is a purine alkaloid derived from caffeine. Like its popular cousin caffeine, theacrine is also able to increase energy, focus, and concentration [25-26]. Additionally, doses of up to 300mg/day theacrine for 8 weeks appears not to have a tachyphylactic/habituation response, which means that it may not be subject to the same tolerance that caffeine is, where you eventually need higher doses of caffeine to feel the same effects [27]. This promising alkaloid is the perfect complement to caffeine, as it allows you to keep your caffeine dose a bit lower and avoid some tolerance from developing. Studies using theacrine alone tend to use 100-300mg, but theacrine is probably most often used in addition to caffeine to provide a boost, with doses of 50-100mg being common additions to caffeine.
Safety of Caffeine Consumption
Caffeine is likely the most often ingested pharmacologically active substance known to man. A review of published human studies concluded that moderate daily caffeine intake at a dose of up to 400mg/day (6mg/kg body weight for a 65kg human) is not associated with adverse effects including general toxicity, cardiovascular effects, effects on bones status, changes in adult behavior, or increased incidence of cancer and effects on male infertility. This review also concluded that reproductive-aged women should consume no more than 300mg/day caffeine (4.6mg/kg for a 65kg woman) [28]. With this in mind, it seems safe to say that there is really no need to go above 400mg/day caffeine for men, or 300mg/day for women, especially considering that all of the benefits of caffeine, including improving energy, focus, reaction time, cognition, and exercise performance, are all obtainable without going above these doses.
Update:
It seems a lot of people are interested in knowing what the highest amount of caffeine that is "safe/reasonable/etc" is. As mentioned earlier, the 400mg/day for men and 300mg/day for reproductive-aged women is a good "safe" amount (assuming average weight, no medical conditions, etc). With that said, a lot of people will/do go over 400mg/day, but I'd still caution you that if you do go above 400mg, which may not be the best idea for chronic (very long term) use, do not exceed 600mg/day, which is supported by the following summary from the U.S. Army's formulations for military operations:
https://www.ncbi.nlm.nih.gov/books/NBK223789/High doses of caffeine can have a negative effect on mood and cognitive performance, and thus the maximum content of caffeine in the delivery form of choice should not exceed 600 mg.
Summary: Dosing/Stacking Guide
Caffeine
Energy, Focus, Alertness, Reaction Time: (50-300mg)
Doses as low as 50mg have shown benefits, but 200-300mg may be preferable for more physically demanding or intensive activities
Exercise Performance: Endurance, Power Output, Improved Time (200-400mg)
3-6mg/kg (~200-400mg for a 150lb person) caffeine has been shown to improve various aspects of exercise performance, with studies noting no significant improvement with 1-2mg/kg (~70-140mg for a 150b person), and one study noting no additional benefits with 6mg/kg (~400mg) compared to 3mg/kg (200mg).
Thermogenesis (100mg +)
Improved thermogenesis and metabolic rate with 100mg, and dose-dependent response up to 400mg
L-Theanine (100-250mg)
Synergistic with caffeine; further improves benefits of caffeine such as reaction time while also reducing potential side effects of caffeine (promotes a calm, focused energy)
L-Ornithine HCL (250mg)
Synergistic with caffeine; improves mood by more than caffeine alone at 8 hours, suggesting it could potentiate the effects of caffeine and the duration of these effect
Choline (see choline article)
Caffeine is able to enhance choline’s ability to release acetylcholine
Carnitine (1-2g +)
Caffeine may be able to increase carnitine’s benefits on exhaustion time and fat oxidation
Theacrine (50+mg, preferably as a “boost” to caffeine, so dose accordingly)
A purine alkaloid derived from caffeine. Possesses similar effects as caffeine, but may not be subject to the same habituation/tolerance that caffeine is
References:
1 https://www.ncbi.nlm.nih.gov/books/NBK223808/
2. http://www.ncbi.nlm.nih.gov/pubmed/18681988
3. https://www.ncbi.nlm.nih.gov/pubmed/20521321
4. https://www.ncbi.nlm.nih.gov/pubmed/762339
5. http://www.ncbi.nlm.nih.gov/pubmed/18006208
6. http://www.ncbi.nlm.nih.gov/pubmed/26869148
7. http://www.tandfonline.com/doi/pdf/10.1080/0014013032000121606
8. https://www.ntis.gov/Search/Home/titleDetail/?abbr=ADA387188
9. http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier=ADA331982
10. http://www.ncbi.nlm.nih.gov/pubmed/12688447
11. https://www.ncbi.nlm.nih.gov/pubmed/20737165
12. https://www.ncbi.nlm.nih.gov/pubmed/22569090
13. https://www.ncbi.nlm.nih.gov/pubmed/20421833
14. https://www.ncbi.nlm.nih.gov/pubmed/22142020
15. https://www.ncbi.nlm.nih.gov/pubmed/18799995
16. https://www.ncbi.nlm.nih.gov/pubmed/21799214
17. https://www.ncbi.nlm.nih.gov/pubmed/2912010
18. https://www.ncbi.nlm.nih.gov/pubmed/2333832
19. http://www.ncbi.nlm.nih.gov/pubmed/18006208
20. https://www.ncbi.nlm.nih.gov/pubmed/18681988
21. http://www.ncbi.nlm.nih.gov/pubmed/21040626
22. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287333/
23. https://www.ncbi.nlm.nih.gov/pubmed/1435067
24. https://www.ncbi.nlm.nih.gov/pubmed/11922111
25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711067/
26. https://www.ncbi.nlm.nih.gov/labs/articles/27164220/
27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271659/
28. https://www.ncbi.nlm.nih.gov/pubmed/12519715
Edit: Additions:
Ephedrine and Caffeine (EC) Stack
Commonly 200mg caffeine and 20mg ephedrine three times daily
*note: Ephedrine is not considered a "supplement" in the United States, and may not be in other areas. Be sure to obey all laws where you live. The following is purely scientific information, not advocating/condoning/etc anything.
The combination of Ephedrine and Caffeine, commonly referred to as an EC stack (or ECA when Aspirin is added, which will not be discussed here), is a common and effective stack for fat-loss. Ephedrine and caffeine are synergistic, with studies noting that while neither caffeine (200mg 3x daily) or ephedrine (20mg 3x daily) were effective for the treatment of obesity, the combination of 200mg caffeine and 20mg ephedrine 3x daily was. Additionally, side effects (tremor, insomnia and dizziness) were transient, and after 8 weeks of use they reached placebo levels [1]. EC has been shown to increase energy expenditure (fat oxidation) while also preserving lean mass (muscle) [2,4]. This combination is often used for somewhat long periods of time (studies have used EC daily for at least 24 weeks), and research suggests that "the side-effects are minor and transient and no clinically relevant withdrawal symptoms have been observed," and "the ephedrine/caffeine combination is safe and effective in long-term treatment in improving and maintaining weight loss" [3]. Additionally, "the hemodynamic and side effects to E+C are transient during chronic treatment, while the effect on energy expenditure persists. The compound also possesses repartitioning properties, which may be useful in the treatment of obesity" [5]. In healthy, lean subjects, the thermogenic effect of 20mg E and 200mg C was greater than 10 or 20mg E alone, 100 or 200mg C alone, and also greater than 10mg E + 200mg C or 20mg E and 100mg C (supra-additive synergism for the 20/200mg dose, with only additive effects at the other doses). Additionally, all three combinations of E&C resulted in a 3-hour postintake increase in systolic blood pressure of 5-7 mm Hg more than placebo. Diastolic blood pressure was not increased by 20/200mg, while the other two combinations increased it by around 4mm Hg more than placebo. Finally, 20mg E and 200mg C (and 20mg E and 100mg C) increased heartrate more than placebo, while 10mg E + 200mg C had no effect on heartrate [6].
1: https://www.ncbi.nlm.nih.gov/pubmed/1318281
2: https://www.ncbi.nlm.nih.gov/pubmed/1619985
3: https://www.ncbi.nlm.nih.gov/pubmed/8124407
4: https://www.ncbi.nlm.nih.gov/pubmed/8384186
5: https://www.ncbi.nlm.nih.gov/pubmed/8384179
6: https://www.ncbi.nlm.nih.gov/pubmed/2000046