Theobromine

Theobroma cacao
Evidence Level
Limited
4 Clinical Trials
4 Documented Benefits
2/5 Evidence Score

Theobromine is a major compound in cocoa and a chemical relative of caffeine. Compared with caffeine, it reaches peak blood levels more slowly (2 to 3 hours) and has a longer half-life (about 7 to 12 hours). Randomized trials of purified theobromine have measured blood lipids, blood pressure, mood and alertness. LDL cholesterol fell in two of three lipid trials, and HDL cholesterol rose in two of three. Blood pressure results are mixed: a single 700 mg dose lowered blood pressure at 1 hour, but 3 to 12 weeks of daily use did not lower resting blood pressure, and a cocoa drink supplying 979 mg/day for 3 weeks raised 24-hour systolic pressure by 3.2 mmHg versus placebo. In three acute trials, theobromine did not raise alertness the way caffeine did, and higher doses worsened mood and raised heart rate. It is toxic to dogs and cats.

Studied Dose Single doses of 100 to 1,000 mg in mood trials; 450 to 850 mg/day for 4 to 12 weeks in lipid trials; 979 mg/day for 3 weeks in a blood pressure trial. Reaching 1,000 mg from chocolate would take three to five 40 g dark chocolate bars.
Active Compound Theobromine (3,7-dimethylxanthine), the major methylxanthine in cocoa and dark chocolate.

Benefits

Blood Pressure: A Brief Acute Dip, No Lasting Drop

A single 700 mg dose lowered blood pressure at 1 hour in 24 healthy women, and 4 weeks at 500 mg/day slightly lowered central augmentation index, a measure of arterial wave reflection. Daily use did not lower resting blood pressure: 12 weeks at 450 mg/day changed neither systolic nor diastolic pressure, and a cocoa drink supplying 979 mg/day for 3 weeks raised 24-hour systolic pressure by 3.2 mmHg versus placebo.

Alertness and Mood Compared With Caffeine

Theobromine is cleared more slowly than caffeine but did not raise alertness the way caffeine did in three controlled trials. In 24 women, caffeine 120 mg raised alertness while theobromine 700 mg did not and lowered calmness at 3 hours. In 24 men, 100 to 400 mg did not consistently change mood or vigilance. In 80 adults, 250 mg had limited effects while higher doses worsened mood and raised heart rate.

HDL Cholesterol: Raised in Two Trials, Not in a Third

Two randomized trials found an HDL rise: 850 mg/day for 4 weeks raised HDL by 0.16 mmol/L in 152 adults aged 40 to 70, and 450 mg/day for 12 weeks with a low-calorie diet raised it by 1.72 mg/dL in 72 adults with metabolic syndrome. A 4-week crossover at 500 mg/day in 44 adults with low HDL found only a trend and no change in HDL subclasses. LDL fell in both 4-week trials but not in the 12-week trial.

Weaker Stimulant Signature Than Caffeine, But Not Calming

Theobromine shows a smaller stimulant effect than caffeine in controlled trials, but that is not the same as a calming effect. The one trial that measured calmness found 700 mg reduced it at 3 hours, and the 80-person dose-ranging trial found worse mood at the higher doses, so the data do not support describing it as a smoother lift than caffeine.

Mechanism of action

1

Adenosine Receptor Binding

Like caffeine, theobromine crosses into the brain and binds adenosine receptors. It enters the brain less readily than caffeine and is a weaker phosphodiesterase inhibitor, which fits its much smaller effect on alertness in trials.

2

Effects on Artery Diameter and Wave Reflection

In a 4-week trial at 500 mg/day, theobromine widened the brachial artery after a meal and lowered augmentation index, but did not improve endothelial function measured by flow-mediated dilation. Resting blood pressure did not fall over 3 to 12 weeks of daily use.

3

Airway and Cough Effects Not Shown in a Trial

Theobromine was tested as a cough product: in 289 adults with persistent cough, twice-daily use for 14 days did not significantly improve the cough quality-of-life endpoint, cough severity or pulmonary function compared with placebo.

Clinical trials

1
Single-Dose Theobromine vs Caffeine on Mood, Psychomotor Performance and Blood Pressure (24 Women)
PubMed

Randomized crossover study comparing theobromine 700 mg, caffeine 120 mg, the combination, and placebo on mood, psychomotor performance and blood pressure measured up to 3 hours post-dose. (Mitchell et al. 2011, Physiol Behav)

24 healthy female adults, randomized crossover design.

Theobromine 700 mg lowered blood pressure relative to placebo at 1 hour and decreased self-reported calmness at 3 hours. Caffeine, not theobromine, raised self-reported alertness at 1, 2 and 3 hours and contentedness at 1 and 2 hours, and caffeine raised blood pressure at 1 hour. There was no treatment effect on Digit Symbol Substitution Test performance in any arm. Combined theobromine and caffeine matched caffeine's mood effects but lost the blood-pressure-lowering signal, suggesting partly independent peripheral and central mechanisms.

2
Psychopharmacology of Theobromine in Healthy Volunteers
PubMed

Within-subjects placebo-controlled study of oral theobromine 250, 500 and 1,000 mg with caffeine 200 mg as active control, with subjective and cardiovascular measures over several hours. (Baggott et al. 2013, Psychopharmacology (Berl))

80 healthy adults, within-subjects placebo-controlled design.

Caffeine produced expected alertness and cardiovascular changes. Theobromine effects were dose-dependent: limited subjective effects at 250 mg and negative mood effects at the higher doses, not only the top dose, and heart rate rose as the dose rose. The data clarify that theobromine has a different and milder psychopharmacological profile than caffeine.

3
Pure Theobromine and Cocoa on HDL Cholesterol (152 Adults)
PubMed

Two-center, double-blind, randomized, placebo-controlled factorial trial of a daily drink with cocoa, 850 mg pure theobromine, both, or neither for 4 weeks. (Neufingerl et al. 2013, Am J Clin Nutr)

152 healthy men and women aged 40 to 70.

Theobromine raised HDL cholesterol by 0.16 mmol/L and apolipoprotein A-I and lowered apolipoprotein B and LDL cholesterol. Cocoa alone had no significant effect. The trial was run by Unilever researchers.

4
Theobromine-Enriched Cocoa and 24-Hour Blood Pressure
PubMed

Double-blind, placebo-controlled 3-period crossover trial of dairy drinks with placebo, cocoa with 106 mg theobromine, or cocoa enriched to 979 mg theobromine, each for 3 weeks. (van den Bogaard et al. 2010, Hypertension)

42 adults aged about 62 with office blood pressure of 130 to 159 / 85 to 99 mmHg.

The primary outcome, 24-hour ambulatory systolic blood pressure, was 3.2 mmHg higher with theobromine-enriched cocoa than placebo. Two hours after a drink, central systolic pressure was 4.3 mmHg lower. The natural-dose cocoa changed neither.

Side effects and drug interactions

Common Potential side effects

Headache, reported most often after a 1,000 mg dose.
Nausea, mostly after 1,000 mg; one participant vomited at that dose.
Faster heart rate as the dose rises, and worse mood at 500 mg and above.
Sleep disturbance is possible if taken late in the day, since its half-life is about 7 to 12 hours.
Toxic to dogs and cats. Theobromine is the compound that makes chocolate dangerous to pets, and dogs clear it far more slowly than people do. Ingestion causes vomiting, restlessness, rapid heart rate, tremors, seizures and can be fatal, and a bulk theobromine or cocoa-extract powder is far more concentrated per scoop than chocolate. Store it sealed and out of reach, and call a veterinarian or a pet poison line at once if an animal swallows any.

Important Drug interactions

Additive effects with other methylxanthines such as caffeine.
Methylxanthine medicines such as theophylline: effects may add up, so ask a prescriber.
Effects on blood pressure are inconsistent, so anyone on blood-pressure medication should tell a prescriber: a single dose lowered blood pressure briefly, while 3 weeks of a theobromine-enriched cocoa drink raised 24-hour ambulatory systolic pressure by 3.2 mmHg.

Frequently asked questions about Theobromine

What is theobromine used for?

Theobromine is a mild stimulant compound found in cocoa, related to caffeine but much weaker. It is sold for energy and cardiovascular support, but controlled trials do not back the energy part: it did not raise alertness or vigilance in any of the three trials that measured it, and it worsened mood at higher doses. In randomized trials, LDL cholesterol fell in two of three lipid trials and HDL rose in two of three.

How is theobromine different from caffeine?

Theobromine is a much weaker central stimulant than caffeine and is cleared more slowly. In head-to-head trials caffeine raised alertness and theobromine did not, and theobromine lowered self-rated calmness at 3 hours and produced negative mood at 500 mg and above. It also raised heart rate as the dose rose. It is not a smoother version of caffeine's alertness effect, because in these trials that effect was not there.

How much theobromine should I take?

Randomized trials used 450 to 979 mg per day for 3 to 12 weeks, and single doses of 100 to 1,000 mg in the acute mood studies. Negative mood effects appeared at 500 mg and above in the dose-ranging trial, and headache and nausea were most common at 1,000 mg. Reaching 1,000 mg from chocolate would take three to five 40 g dark chocolate bars.

Is theobromine safe?

In trials, theobromine was generally tolerated, though a 1,000 mg dose caused headache and nausea in some people and higher doses raised heart rate. Theobromine is toxic to dogs and other pets, which is why chocolate is dangerous for them, so keep it away from animals.

What is Theobromine?

Theobromine is a major compound in cocoa and a chemical relative of caffeine. Compared with caffeine, it reaches peak blood levels more slowly (2 to 3 hours) and has a longer half-life (about 7 to 12 hours). Randomized trials of purified theobromine have measured blood lipids, blood pressure, mood and alertness.

What is the recommended dosage of Theobromine?

The clinically studied dose is Single doses of 100 to 1,000 mg in mood trials; 450 to 850 mg/day for 4 to 12 weeks in lipid trials; 979 mg/day for 3 weeks in a blood pressure trial. Reaching 1,000 mg from chocolate would take three to five 40 g dark chocolate bars. Always follow the product label and check with a healthcare provider for personal advice.

Is Theobromine safe, and does it have side effects?

For most healthy adults, Theobromine is well tolerated at studied doses. Reported effects can include: Headache, reported most often after a 1,000 mg dose. Nausea, mostly after 1,000 mg; one participant vomited at that dose. It may also interact with some medications. Theobromine is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Theobromine interact with any medications?

Possible interactions include: Additive effects with other methylxanthines such as caffeine. Methylxanthine medicines such as theophylline: effects may add up, so ask a prescriber. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Theobromine?

NutraSmarts rates the evidence for Theobromine as Limited (2 out of 5). It is backed by 4 clinical trials and 10 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(10 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Mitchell ES, Slettenaar M, vd Meer N, Transler C, Jans L, Quadt F, Berry M. Differential contributions of theobromine and caffeine on mood, psychomotor performance and blood pressure. Physiol Behav. 2011;104(5):816-22. doi: 10.1016/j.physbeh.2011.07.027.PubMedUsed to support: Acute crossover trial in 24 healthy women. Theobromine 700 mg lowered blood pressure versus placebo at 1 hour and lowered self-reported calmness at 3 hours. Caffeine 120 mg, not theobromine, raised self-reported alertness at 1, 2 and 3 hours, and no arm changed Digit Symbol Substitution Test performance. Conducted by Unilever R&D.
  2. Baggott MJ, Childs E, Hart AB, de Bruin E, Palmer AA, Wilkinson JE, de Wit H. Psychopharmacology of theobromine in healthy volunteers. Psychopharmacology (Berl). 2013;228(1):109-18. doi: 10.1007/s00213-013-3021-0.PubMedUsed to support: Within-subjects placebo-controlled trial of single theobromine doses of 250, 500 and 1,000 mg against caffeine 200 mg in 80 healthy adults. Caffeine produced the expected alertness and cardiovascular effects; theobromine produced limited subjective effects at 250 mg, negative mood effects at the higher doses, and a dose-dependent rise in heart rate.
  3. van den Bogaard B, Draijer R, Westerhof BE, van den Meiracker AH, van Montfrans GA, van den Born BJ. Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: a randomized, double-blind crossover trial. Hypertension. 2010;56(5):839-46. doi: 10.1161/HYPERTENSIONAHA.110.158139.PubMedUsed to support: Three-week randomized double-blind crossover trial in 42 adults aged about 62 with mildly raised blood pressure. Theobromine-enriched cocoa supplying 979 mg/day raised 24-hour ambulatory systolic blood pressure by 3.2 mmHg compared with placebo, which was the trial's primary outcome, while lowering central systolic pressure by 4.3 mmHg at 2 hours. Cocoa at its natural theobromine dose of 106 mg changed neither.
  4. Neufingerl N, Zebregs YE, Schuring EA, Trautwein EA. Effect of cocoa and theobromine consumption on serum HDL-cholesterol concentrations: a randomized controlled trial. Am J Clin Nutr. 2013;97(6):1201-9. doi: 10.3945/ajcn.112.047373.PubMedUsed to support: Four-week randomized, double-blind, placebo-controlled factorial trial in 152 healthy adults aged 40 to 70. Pure theobromine at 850 mg/day raised HDL cholesterol by 0.16 mmol/L and apolipoprotein A-I, and lowered apolipoprotein B and LDL cholesterol; cocoa alone had no significant HDL effect. The trial was designed and run by Unilever Research and Development, which sells cocoa products.
  5. Smolders L, Mensink RP, Boekschoten MV, de Ridder RJJ, Plat J. Theobromine does not affect postprandial lipid metabolism and duodenal gene expression, but has unfavorable effects on postprandial glucose and insulin responses in humans. Clin Nutr. 2018;37(2):719-727. doi: 10.1016/j.clnu.2017.06.007.PubMedUsed to support: Four-week randomized double-blind crossover trial of theobromine 500 mg/day in 44 adults with low baseline HDL cholesterol. Fasting LDL cholesterol fell by 0.21 mmol/L and apoB100 by 0.04 g/L, HDL cholesterol only tended to rise, and postprandial glucose, insulin and free fatty acid responses worsened. The authors concluded it is not likely that the potential benefits of cocoa on cardiovascular disease can be ascribed to theobromine.
  6. Sharifi-Zahabi E, Rezvani N, Hajizadeh-Sharafabad F, Hosseini-Baharanchi FS, Shidfar F, Rahimi M. Theobromine supplementation in combination with a low-calorie diet improves cardiovascular risk factors in overweight and obese subjects with metabolic syndrome: a randomized controlled trial. Food Funct. 2023;14(18):8431-8441. doi: 10.1039/d3fo00555k.PubMedUsed to support: Twelve-week randomized double-blind parallel trial of pure theobromine 450 mg/day plus a low-calorie diet in 80 adults aged 40 to 55 with metabolic syndrome, 72 of whom completed. Compared with placebo, theobromine lowered waist circumference by 0.86 cm, improved the LDL/HDL, triglyceride/HDL and total-cholesterol/HDL ratios, and raised HDL cholesterol by 1.72 mg/dL. Body weight, BMI, systolic and diastolic blood pressure, total cholesterol, triglycerides, LDL cholesterol, fasting glucose, insulin and HOMA-IR did not differ from placebo. Both groups also followed a calorie-restricted diet.
  7. Judelson DA, Preston AG, Miller DL, Muñoz CX, Kellogg MD, Lieberman HR. Effects of theobromine and caffeine on mood and vigilance. J Clin Psychopharmacol. 2013;33(4):499-506. doi: 10.1097/JCP.0b013e3182905d24.PubMedUsed to support: Double-blind trial in 24 young men: theobromine at 100, 200 and 400 mg did not consistently affect mood or performance on a 2-hour visual vigilance task, while caffeine 100 mg lowered fatigue and raised vigor.
  8. Smolders L, Mensink RP, van den Driessche JJ, Joris PJ, Plat J. Theobromine consumption does not improve fasting and postprandial vascular function in overweight and obese subjects. Eur J Nutr. 2019;58(3):981-987. doi: 10.1007/s00394-018-1612-6.PubMedUsed to support: Report from the same 4-week crossover in 44 adults with low HDL (500 mg/day): no change in fasting vascular function except a small fall in central augmentation index; after a meal, brachial artery diameter rose and augmentation index fell, but flow-mediated dilation did not improve.
  9. Jacobs DM, Smolders L, Lin Y, de Roo N, Trautwein EA, van Duynhoven J, Mensink RP, Plat J, Mihaleva VV. Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations. Front Mol Biosci. 2017;4:59. doi: 10.3389/fmolb.2017.00059.PubMedUsed to support: Report from the same 44 participants: theobromine 500 mg/day for 4 weeks lowered cholesterol in LDL particles but had no effect on triglyceride or cholesterol in any HDL, VLDL or chylomicron subclass.
  10. Morice AH, McGarvey L, Pavord ID, Higgins B, Chung KF, Birring SS. Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial. J Thorac Dis. 2017;9(7):1864-1872. doi: 10.21037/jtd.2017.06.18.PubMedUsed to support: Randomized double-blind placebo-controlled trial in 289 adults with persistent cough: a theobromine product (BC1036) twice daily for 14 days did not significantly improve cough quality of life, cough severity or pulmonary function versus placebo. Funded by Infirst Healthcare.