Caffeine tolerance

Finally, our genetic variability may make us more or less prone to disease or the effects of a toxic agent. Some can tolerate caffeine before bed, while for others such exposure would result in a restless night. It is always important to consider the individual and the individual characteristics of a situation. 

Destmction of the aluminum complex with ammonia then permits hydrocarbon extraction of the alkaloid. The alkaloid is subsequently both isolated and used as its tartrate salt. This nonnarcotic dmg, for which tolerance may develop, is frequently used orally with caffeine (16) for treatment of migraine it acts to constrict cerebral blood vessels, thus reducing blood flow to the brain. 

The body responds to chronic presence of caffeine by increasing the number of adenosine receptor sites. This may be one of the reasons for the increased tolerance (and decreased efficacy as a stimulant) to caffeine in heavy coffee and tea drinkers. 

Dodd et al.48 tested 17 moderately trained males for V02 max and time to exhaustion on a bicycle ergometer. Experimental trials involved the administration of 3- or 5-mg/kg caffeine 1 h prior to testing. Caffeine had no effect on exercise performance. Since nearly half of the subjects were caffeine naive (<25 mg/d), while the other half were caffeine tolerant (>310 mg/d), the researchers were able to conclude that even though caffeine had no significant effects on performance, it did produce a variety of physiologically significant effects (heart rate and expired ventilation volume) in the caffeine naive group. 

A formal diagnosis of substance dependence requires a maladaptive pattern of abuse that leads to clinically significant impairment or distress. More detailed criteria revolve around the development of tolerance, the experience of withdrawal when abstinence is required, the inability to stop using the drug, and continued use over a protracted period of time. The question is whether or not these criteria, clearly applicable to cocaine, heroin, and other drugs, are met by caffeine. 

A variety of factors differentiating tolerance studies could have contributed to the observed discrepancy. Lower doses are less likely to lead to tolerance than higher doses or will do so less rapidly. The habitual coffee drinkers in some studies may have had different levels or durations of consumption. In the cases of acute dosing, caffeine consumed by subjects outside the laboratory on the day of the experiment may have varied. This is particularly true when some investigators request in advance that subjects abstain from caffeine prior to the experiment, while others do not. Differences in age, gender, and arousal-relevant personality dimensions,... 

Hirsch, A., Gervine, E., Nakso, S., Come, P., Silverman, K. and Grossman, W., The effect of caffeine on exercise tolerance and left ventricular function in patinets with coronary heart disease. Annals of Internal Medicine 110, 593-598, 1989. 

The exact mechanism by which chemical exposures cause MCS is unknown. It is believed that a two-step process occurs. First, an initial exposure or chronic exposures interacts with a susceptible individual, leading to loss of that person s prior, natural tolerance for everyday, low-level chemicals, as well as certain foods, drugs, alcohol, and caffeine. In the second stage, symptoms are thereafter triggered by extremely low doses of previously tolerated products and exposures.2 This theory is called toxicant-induced loss of tolerance or TILT. 3... 

Intracellular messengers A biphasic effect of ginkgo extract is seen on cAMP phosphodiesterase under in vitro and ex vivo conditions (Saponara and Bosisio 1998 Macovschi et al. 1987). Whereas low concentrations (0.25-4.0 mg/L) activate the enzyme, higher concentrations (5-250 mg/L), dose-dependently inhibit it. However, tolerance develops to this effect because it is undetectable after daily administration for 4 days. Thus, ginkgo may initially produce effects by inhibiting enzymatic breakdown of cAMP. This mechanism is similar to the stimulant caffeine, but it is not likely to explain any long-term effects of ginkgo because it disappears after chronic daily treatment. The responsible constituent for this effect has not been identified. 

Dager SR, Layton ME, Strauss W, Richards TL, Heide A, Friedman SD, Artru AA, Hayes CE, Posse S. (1999). Human brain metabolic response to caffeine and the effects of tolerance. Am J Psychiatry. 156(2) 229-37. 

Ahlijanian MK, Takemori AE. (1986). The effect of chronic administration of caffeine on morphine-induced analgesia, tolerance and dependence in mice. EurJ Pharmacol. 120(1) 25-32. 

The caffeine naive individual may notice some changes in heart rate following consumption of a strong cup of coffee. Most caffeine users have developed a tolerance to the cardiovascular effects, but these effects may occur if there is elevated consumption. 

A variety of drugs in distinct pharmacological and chemical classes can be considered under the broad classification as stimulants. Xanthines and methylxan-thines constitute a weak class of stimulants that includes caffeine, theophylline (aminophylline),and theobromine. Caffeine is freely available in coffee, colas, and certain over-the-counter pills. A low degree of tolerance develops to some of their effects and a mild withdrawal syndrome is observed following immediate cessation of their repeated use. 

Kendler, K. S. and C. A. Prescott. Caffeine intake, tolerance, and withdrawal in women a population-based twin study. Am J Psychiatry 1999 156(2) 223-228. 

Johnston, K.L., Clifford, M.N., and Morgan, L.M., Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans glycemic effects of chlorogenic acid and caffeine. Am. J. Clin. Nutr., 78, 728, 2003. 

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