7 Methyl-Xanthines Benefits, Side Effects & Sources

7 Methyl-Xanthines Benefits, Side Effects & Sources

We are all familiar with coffee and caffeine. What you might not know is that caffeine belongs to a wider category of chemical compounds called methylxanthines. These compounds — abundant in cocoa, tea, and coffee — may protect the heart and brain, improve physical performance, boost metabolism, and more. However, their over-consumption can be harmful. Read on to learn the potential benefits, safety precautions, and best natural sources of xanthines. What are Xanthines?

Methylxanthines are chemical compounds derived from the purine base xanthine. Some well-known natural xanthines include caffeine , theobromine , and theophylline .

At least half of the world’s population drinks tea, which contains caffeine and small amounts of theophylline and theobromine [ 1 ].

Cocoa and chocolate, derived from the seeds of Theobroma cacao , contain theobromine, which is the main chemical responsible for their health benefits. Also, some caffeine is present [ 2 , 3 ].

Coffee , the most popular source of dietary caffeine, is extracted from the Arabica coffee and related species.

Caffeine is mainly broken down by the liver and, interestingly, one of its by-products is theobromine [ 4 ].

Methylxanthines, specifically theobromine and caffeine, are the main factors responsible for particular chocolate cravings, revealing their huge impact on taste and food preferences [ 5 ].

If your interest is mainly in caffeine, jump to this post . Mechanisms of Action

1) Mobilization of intracellular calcium

2) Inhibition of phosphodiesterases (PDEs)

3) Inhibition of gamma-aminobutyric acid (GABAA) receptors

4) Inhibition of high affinity ATP-dependent cyclic nucleotide transporters

The predominant health effects that stem from these mechanisms are increased wakefulness and alertness during the day. Methylxanthines also have other effects such as relaxing smooth muscles, stimulating urine production and fluid loss, and increasing heart muscle contraction [ 16 ].

However, much higher doses may be required to mobilize intracellular calcium, inhibit PDEs or modulate GABAA receptors, or to unselectively inhibit ABCC5 and ABCC4 transporters [ 8 , 17 ].

This leaves the action on adenosine receptors and inhibition of cAMP-degradation as the primary mechanism behind the effects of dietary methylxanthines.

To give a practical example: when adenosine accumulates in the brain and saturates adenosine receptors, we feel dizzy and sleepy. Xanthines bind to the same receptors as adenosine (antagonism), which prevents this effect and keeps us alert and awake.

Also, maintaining a high level of circulating cAMP may increase heart rate and promote fat metabolism [ 18 ]. Xanthines Health Benefits

1) Respiratory Conditions

Whether dietary cocoa consumption or methylxanthines are significantly effective in preventing cough or diminishing cough intensity is yet to be determined, however, the evidence is promising [ 19 , 20 ].

Theophylline is an active component of different FDA-approved drugs for asthma and other respiratory conditions [ 21 ].

Theobromine may be helpful for asthma, cough, and other respiratory tract problems, too.

A clinical trial of 289 subjects (DB-RCT) showed a mild improvement in a persistent cough with the use of a theobromine-based compound [ 22 ].

In a study of 21 young adults with asthma, theobromine capsules increased bronchial diameter, which increased airflow to the lungs [ 23 ].

The anti-inflammatory potential of theobromine may be responsible for this effect. It can reduce the levels of inflammatory cytokines such as IFN-y and TNF-a [ 2 , 24 ].

According to a review of 7 clinical studies, caffeine can help open the airways and relieve bronchitis symptoms including wheezing, coughing, and breathlessness [ 25 ]. 2) Attention and Alertness

Multiple clinical reviews have confirmed the potential of caffeine to increase mental alertness in low-to-moderate doses (40-300 mg). The effects were even more pronounced in non-regular users and during sleep deprivation [ 26 , 27 , 28 ].In a study of 36 participants, caffeine exhibited dose-dependent effects on alertness and attention. When people who usually do not drink caffeinated products consumed high doses of caffeine, they had a higher increase in brain function. Regular and tolerant users may still feel the same effects, but to a smaller extent [ 29 ].A lack of sleep can cause delays in reaction times. In a study of 20 sleep-deprived participants, a total daily dose of 800 mg of caffeine helped improve reaction speed and accuracy [ 30 ].In one study, twelve young adults either had sufficient sleep (9 hours) or a lack-of-sleep (4 hours). 100 mg of caffeine improved both groups’ coordination, judgment, memory, and reaction time during a driving task [ 31 ].However, some reviews have underlined the tolerance to its stimulant effects, abuse potential, and a potential toxicity that comes with higher doses [ 32 , 33 ]. 3) Physical Performance A comprehensive clinical review summarized 21 meta-analyses on caffeine and physical performance. A large body of evidence suggests that “ caffeine ingestion improves exercise performance in a broad range of exercise tasks .” It showed beneficial effects on [ 34 ]: Muscle endurance Muscle strength Aerobic endurance Anaerobic power Caffeine particularly helps anaerobic exercises like sprinting or jumping. This effect may arise from its anti-fatigue effects and by improving endurance, physical strength, and power output [ 35 ].In a small study of 10 healthy subjects, theophylline delayed the onset of fatigue during intermittent high-intensity exercise [ 36 ]. 4) Heart Disease A recent review of 14 studies found that moderate chocolate consumption (up to 6 servings or 180 g per week) reduced the risk of heart disease and stroke [ 37 ].Two different reviews found a protective role for cocoa and its major compound, theobromine, in metabolic and heart health [ 38 , 39 ]. Circulation (Blood Flow) High cholesterol, metabolic syndrome, and blood vessel stiffness are common in postmenopausal women. Chronic consumption of flavanol-rich cocoa enhanced blood circulation in postmenopausal women with high cholesterol [ 40 , 41 , 42 , 43 ].Methylxanthines are able to increase the blood concentration of a particular chemical compound called (-)-epicatechin, which may also improve blood circulation [ 44 ].Theobromine, abundant in cocoa, may cause blood pressure to decrease by widening the blood vessels and stimulating urination (diuretic) [ 45 ]. Cholesterol Levels […]

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