Did your doctor and stroke hospital initiate research into this in humans? It has only been over 13 years for them to completely prove their incompetency and with a board of directors that is not directing them properly.
Does Coffee and Alcohol (Caffeinol) Prevent and Reduce Severity of Strokes?
When coffee was first introduced in Europe in the 1600's, it was
regarded as a mysterious elixir that had all sorts of good effects on
the body. While many people have attributed the effects of coffee to
caffeine, one of its ingredients, there are many who say that drinking
tea (which also has caffeine) does not do the same things for them as
coffee. So, what does coffee have and what effect does it have on our
bodies? The subject is huge and therefore I will only focus on part of
the story and post more if there is interest and discussion.
Coffee is known to stimulate the central nervous system. For those who are not use to drinking coffee regularly, it seems to make people more nervous. Part of this "nervousness" comes from a reduction in the threshold of neurons and muscles to activation. Finally, it is fairly well accepted that coffee increases release of fatty acids by cells. Since fatty acids are a source of energy, some athletes drink coffee. At least one study suggests that cyclists who drank caffeinated coffee took longer to reach exhaustion and "felt better" than those who drank decaffeinated coffee (Source).
Unfortunately, most studies of coffee use are correlative and not controlled studies. For example, one study in the Journal of Clinical Epidemiology reported that men who drink 3 or more cups of coffee a day at age 55-68, had a higher risk of developing thromboembolic stroke (Source but other studies suggest that drinking five or more cups of coffe a day reduced the likelihood of stroke by 69% (Source). Flavenoids and antioxidants in the coffee are thought to be responsible. At least one study showed that a combination of alcohol and caffeine (called caffeinol) significantly reduced stroke severity in rats (Source).
Several more recent studies have reinforced the observation that coffee and alcohol together is neuroprotective. In 2004, Dash, et al. reported that post-trauma administration of caffeine plus ethanol significantly reduces contusion volume and improves working memory in rats after brain injury. In 2005, Zhao, et al. reported that combining insulin-like growth factor derivatives plus caffeinol produces robust protection after stroke in rats. Lapchek, et al. (2004), however, found that caffeinol does not improve recovery may increase the incidence of hemorrhagic stroke from emboli. Hoyt, et al. (2004) showed that caffienol may increase hemorrhage when combined with thrombolytics (drugs the dissolve clots. Belayev, et al. (2004) reported that caffeinol protects cortical areas of the brain from focal ischemia but did not protect subcortical structures. These studies were strongly stimulated by a report from Aronowski, et al. (2003) who conducted five sets of experiments to evaluate caffeinol as a treatment for acute stroke and concluded that low doses of caffeinol, equivalent to 3 cups of coffee and 1 cocktail are "consistently and highly neuroprotective, are well tolerated, can be added to other therapies to increase the effects of each, and do not interfere with or complicate rtPA therapy."
Piriyawat, et al. (2003) published an initial dose-escalation clinical trial where they gave patients increasing doses of caffeine and ethanol after acute ischemic stroke. One group received 6 mg/kg and 0.2 g/kg of caffeine and alcohol, another 8 mg/kg and 0.4 g/kg, and a third group 10 mg/kg and 0.6 g/kg. They showed that these doses can be given safely to patients after stroke. That study was conducted three years ago and one wonders why this treatment has not yet gone into randomized clinical trials. A search of www.clinicaltrails.gov revealed only one non-randomized study that is ongoing, assessing the effects of combined caffeinol and hypothermia treatments of acute stroke in Texas (Source). It will be interesting to see what the results of this trial show.
References Cited
Coffee is known to stimulate the central nervous system. For those who are not use to drinking coffee regularly, it seems to make people more nervous. Part of this "nervousness" comes from a reduction in the threshold of neurons and muscles to activation. Finally, it is fairly well accepted that coffee increases release of fatty acids by cells. Since fatty acids are a source of energy, some athletes drink coffee. At least one study suggests that cyclists who drank caffeinated coffee took longer to reach exhaustion and "felt better" than those who drank decaffeinated coffee (Source).
Unfortunately, most studies of coffee use are correlative and not controlled studies. For example, one study in the Journal of Clinical Epidemiology reported that men who drink 3 or more cups of coffee a day at age 55-68, had a higher risk of developing thromboembolic stroke (Source but other studies suggest that drinking five or more cups of coffe a day reduced the likelihood of stroke by 69% (Source). Flavenoids and antioxidants in the coffee are thought to be responsible. At least one study showed that a combination of alcohol and caffeine (called caffeinol) significantly reduced stroke severity in rats (Source).
Several more recent studies have reinforced the observation that coffee and alcohol together is neuroprotective. In 2004, Dash, et al. reported that post-trauma administration of caffeine plus ethanol significantly reduces contusion volume and improves working memory in rats after brain injury. In 2005, Zhao, et al. reported that combining insulin-like growth factor derivatives plus caffeinol produces robust protection after stroke in rats. Lapchek, et al. (2004), however, found that caffeinol does not improve recovery may increase the incidence of hemorrhagic stroke from emboli. Hoyt, et al. (2004) showed that caffienol may increase hemorrhage when combined with thrombolytics (drugs the dissolve clots. Belayev, et al. (2004) reported that caffeinol protects cortical areas of the brain from focal ischemia but did not protect subcortical structures. These studies were strongly stimulated by a report from Aronowski, et al. (2003) who conducted five sets of experiments to evaluate caffeinol as a treatment for acute stroke and concluded that low doses of caffeinol, equivalent to 3 cups of coffee and 1 cocktail are "consistently and highly neuroprotective, are well tolerated, can be added to other therapies to increase the effects of each, and do not interfere with or complicate rtPA therapy."
Piriyawat, et al. (2003) published an initial dose-escalation clinical trial where they gave patients increasing doses of caffeine and ethanol after acute ischemic stroke. One group received 6 mg/kg and 0.2 g/kg of caffeine and alcohol, another 8 mg/kg and 0.4 g/kg, and a third group 10 mg/kg and 0.6 g/kg. They showed that these doses can be given safely to patients after stroke. That study was conducted three years ago and one wonders why this treatment has not yet gone into randomized clinical trials. A search of www.clinicaltrails.gov revealed only one non-randomized study that is ongoing, assessing the effects of combined caffeinol and hypothermia treatments of acute stroke in Texas (Source). It will be interesting to see what the results of this trial show.
References Cited
- Dash PK, Moore AN, Moody MR, Treadwell R, Felix JL and Clifton GL (2004). Post-trauma administration of caffeine plus ethanol reduces contusion volume and improves working memory in rats. J Neurotrauma 21: 1573-83. It has been demonstrated that ethanol exerts dose-dependent effects, both beneficial and detrimental, on the outcome of traumatic brain injury (TBI). Recently, it has been reported that co-administration of caffeine (10 mg/kg) and a low amount of alcohol (0.65 g/kg; caffeinol) reduces cortical infarct volume up to 80%, and improves motor coordination, following a rodent model of reversible common carotid/middle cerebral artery occlusion. However, the protective effects of caffeinol following other CNS insults, nor its influence on cognitive function, have been examined. Using a controlled cortical impact model of brain injury, the effect of caffeinol administration on TBI-associated motor and cognitive deficits was assessed. When given 15 min following injury, caffeinol reduced cortical tissue loss and improved working memory. However, no influence on motor skills, Morris water maze performance or associative learning and memory was observed. Delayed administration (6 h post-injury) of caffeinol containing a dose of ethanol (1 g/kg) previously demonstrated to improve motor performance eliminated the working memory benefit and cortical protection. These results indicate that early administration of caffeinol may be beneficial in lessening some of the deficits and cortical tissue loss associated with brain trauma. Vivian L. Smith Center for Neurologic Research, Department of Neurobiology and Anatomy, University of Texas Medical School, Houston, Texas 77225, USA. p.dash@uth.tmc.edu http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15684650
- Zhao X, Liu SJ, Zhang J, Strong R, Aronowski J and Grotta JC (2005). Combining insulin-like growth factor derivatives plus caffeinol produces robust neuroprotection after stroke in rats. Stroke 36: 129-34. BACKGROUND AND PURPOSE: Insulin-like growth factor-1 (IGF-1) and caffeinol are both neuroprotective and probably have different mechanisms of action; therefore, they may be more effective in combination. METHODS: We tested the N-terminal tripeptide of IGF-1, Gly-Pro-Glu (GPE), and its analogue, G2MePE, alone and with caffeinol in a rat middle cerebral artery (MCA) suture occlusion model. We randomly assigned rats to 6 groups of 8 to 12 animals: (1) control; (2) GPE, 3 mg/kg per hour; (3) G2MePE, 0.3 mg/kg per hour; (4) caffeinol, a mixture of caffeine (10 mg/kg) with ethanol (0.32 g/kg); (5) GPE with caffeinol (combination of group 2 with 4); and (6) G2MePE with caffeinol (combination of group 3 with 4). Drugs were started 75 minutes after suture occlusion, at the start of reperfusion. Three days after MCA occlusion, neurological deficit (Neurological Deficit Score [NDS]) and lesion volume were measured. RESULTS: GPE and caffeinol improved NDS by 34% and 36%, respectively (P<0.01), and also decreased cortical but not striatal lesion volume compared with control (GPE cortex, 121 mm3; caffeinol cortex, 134 mm3; and control, 221 mm3; P<0.01). GPE plus caffeinol did not have more efficacy than either GPE or caffeinol alone. G2MePE slightly improved NDS (19.7%, P=0.05) but not lesion volume. However, G2MePE plus caffeinol very significantly improved NDS (64%) and lesion volume in both cortex (combination 95 mm3 versus control 221 mm3) and striatum (combination 74 mm3 versus control 110 mm3) (P<0.001), and was significantly more effective than either caffeinol or G2MePE alone. CONCLUSIONS: Both GPE and caffeinol significantly protect cortex after MCA occlusion. At the doses used in this study, the GPE analogue G2MePE by itself had minimal protective effects, but when combined with caffeinol, it demonstrated robust beneficial effects on cortical and subcortical lesion size and behavioral deficit. Further study of this combination appears justified. Vascular Neurology Program, Department of Neurology, University of Texas-Houston Medical School, Houston, Tex 77030, USA. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15569874
- Lapchak PA, Song D, Wei J and Zivin JA (2004). Pharmacology of caffeinol in embolized rabbits: clinical rating scores and intracerebral hemorrhage incidence. Exp Neurol 188: 286-91. Caffeinol is currently being tested in acute ischemic stroke patients. However, little is known about the pharmacology or safety of caffeinol in preclinical embolic stroke models. We determined the pharmacological effects of caffeinol administration on clinical rating scores in rabbits following small clot embolic strokes (RSCEM). Male New Zealand white rabbits were embolized by injecting blood clots into the cerebral circulation via a carotid catheter. Behavioral analysis was conducted 24 h following embolization, allowing for the determination of the effective stroke dose (P50) or clot amount (mg) that produces neurological deficits in 50% of the rabbits. In the current study, the P50 values for the control groups were 1.32 +/- 0.23 and 1.66 +/- 0.29 mg for the bolus-injected and infused groups, respectively. Rabbits treated with caffeinol (bolus) starting 15 min following embolization had a P50 value of 1.70 +/- 1.18 mg. Caffeinol-infused rabbits had a P50 value of 2.05 +/- 0.47 and 1.67 +/- 0.48 mg for low- and high-dose ethanol, respectively. In tPA-treated rabbits (0.9 mg/kg), the group P50 was 1.58 +/- 0.43 mg. In caffeinol (bolus) and tPA-treated rabbits, we measured a decrease in the P50 value to 0.70 +/- 0.30 mg and an increase in the rate of intracerebral hemorrhage compared to control. This primary finding of this study indicates that neither bolus-injected nor infused caffeinol affects behavioral deficits following embolic strokes in rabbits. Moreover, the combination of caffeinol plus low-dose tPA does not improve behavioral deficits. However, our study suggests that there is the potential for exacerbation of stroke-induced behavioral deficits following caffeinol administration in combination with a thrombolytic that may be related to increased intracerebral hemorrhage. University of California San-Diego, Department of Neuroscience, La Jolla 92093-0624, USA. plapchak@ucsd.edu http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15246828
- Lapchak PA, Song D, Wei J and Zivin JA (2004). Pharmacology of caffeinol in embolized rabbits: clinical rating scores and intracerebral hemorrhage incidence. Exp Neurol 188: 286-91. Caffeinol is currently being tested in acute ischemic stroke patients. However, little is known about the pharmacology or safety of caffeinol in preclinical embolic stroke models. We determined the pharmacological effects of caffeinol administration on clinical rating scores in rabbits following small clot embolic strokes (RSCEM). Male New Zealand white rabbits were embolized by injecting blood clots into the cerebral circulation via a carotid catheter. Behavioral analysis was conducted 24 h following embolization, allowing for the determination of the effective stroke dose (P50) or clot amount (mg) that produces neurological deficits in 50% of the rabbits. In the current study, the P50 values for the control groups were 1.32 +/- 0.23 and 1.66 +/- 0.29 mg for the bolus-injected and infused groups, respectively. Rabbits treated with caffeinol (bolus) starting 15 min following embolization had a P50 value of 1.70 +/- 1.18 mg. Caffeinol-infused rabbits had a P50 value of 2.05 +/- 0.47 and 1.67 +/- 0.48 mg for low- and high-dose ethanol, respectively. In tPA-treated rabbits (0.9 mg/kg), the group P50 was 1.58 +/- 0.43 mg. In caffeinol (bolus) and tPA-treated rabbits, we measured a decrease in the P50 value to 0.70 +/- 0.30 mg and an increase in the rate of intracerebral hemorrhage compared to control. This primary finding of this study indicates that neither bolus-injected nor infused caffeinol affects behavioral deficits following embolic strokes in rabbits. Moreover, the combination of caffeinol plus low-dose tPA does not improve behavioral deficits. However, our study suggests that there is the potential for exacerbation of stroke-induced behavioral deficits following caffeinol administration in combination with a thrombolytic that may be related to increased intracerebral hemorrhage. University of California San-Diego, Department of Neuroscience, La Jolla 92093-0624, USA. plapchak@ucsd.edu http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15246828
- Lapchak PA, Song D, Wei J and Zivin JA (2004). Pharmacology of caffeinol in embolized rabbits: clinical rating scores and intracerebral hemorrhage incidence. Exp Neurol 188: 286-91. Caffeinol is currently being tested in acute ischemic stroke patients. However, little is known about the pharmacology or safety of caffeinol in preclinical embolic stroke models. We determined the pharmacological effects of caffeinol administration on clinical rating scores in rabbits following small clot embolic strokes (RSCEM). Male New Zealand white rabbits were embolized by injecting blood clots into the cerebral circulation via a carotid catheter. Behavioral analysis was conducted 24 h following embolization, allowing for the determination of the effective stroke dose (P50) or clot amount (mg) that produces neurological deficits in 50% of the rabbits. In the current study, the P50 values for the control groups were 1.32 +/- 0.23 and 1.66 +/- 0.29 mg for the bolus-injected and infused groups, respectively. Rabbits treated with caffeinol (bolus) starting 15 min following embolization had a P50 value of 1.70 +/- 1.18 mg. Caffeinol-infused rabbits had a P50 value of 2.05 +/- 0.47 and 1.67 +/- 0.48 mg for low- and high-dose ethanol, respectively. In tPA-treated rabbits (0.9 mg/kg), the group P50 was 1.58 +/- 0.43 mg. In caffeinol (bolus) and tPA-treated rabbits, we measured a decrease in the P50 value to 0.70 +/- 0.30 mg and an increase in the rate of intracerebral hemorrhage compared to control. This primary finding of this study indicates that neither bolus-injected nor infused caffeinol affects behavioral deficits following embolic strokes in rabbits. Moreover, the combination of caffeinol plus low-dose tPA does not improve behavioral deficits. However, our study suggests that there is the potential for exacerbation of stroke-induced behavioral deficits following caffeinol administration in combination with a thrombolytic that may be related to increased intracerebral hemorrhage. University of California San-Diego, Department of Neuroscience, La Jolla 92093-0624, USA. plapchak@ucsd.edu http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15246828
- Piriyawat P, Labiche LA, Burgin WS, Aronowski JA and Grotta JC (2003). Pilot dose-escalation study of caffeine plus ethanol (caffeinol) in acute ischemic stroke. Stroke 34: 1242-5. BACKGROUND AND PURPOSE: In animal models, the combination of caffeine and ethanol (caffeinol) provides robust neuroprotection at blood levels that should be easily and safely achieved in humans. This study was designed to determine the safety and tolerability of ascending doses of this combination in stroke patients. METHODS: This Food and Drug Administration-approved open-label, single-arm, dose-escalation study had 3 original dose groups: group 1, caffeine 6 mg/kg plus ethanol 0.2 g/kg; groups 2 and 3, incremental increases of caffeine and ethanol by 2 mg/kg and 0.2 g/kg, respectively. Intravenous thrombolysis was encouraged if patients qualified. Drug was started within 6 hours of stroke onset, and blood levels of caffeine and ethanol were drawn at baseline and end of infusion. The target blood caffeine and ethanol ranges were 8 to 10 microg/mL and 30 to 50 mg/dL, respectively. Clinical outcome measurements included the National Institutes of Health Stroke Scale at the end of infusion, at 24 hours, and at discharge. Potential complications from caffeine and ethanol were recorded. Cases were reviewed by an independent stroke neurologist for safety. RESULTS: A total of 23 patients were recruited. Target blood caffeine and ethanol levels were reached in 0 of the 4 patients in the first group. The second dose group (caffeine 8 mg/kg plus ethanol 0.4 g/kg) included 8 patients. The median end-of-infusion caffeine and ethanol levels were within the desired target ranges. Two days after infusion, 1 patient in this group with preexisting cardiac disease and end-of-infusion caffeine and ethanol levels of 10.7 microg/mL and 69 mg/dL developed reversible congestive heart failure and required transfer to an intensive care unit. The original third dose group was canceled given achievement of target blood caffeine and ethanol levels in group 2. However, 3 new dose groups were created in an attempt to minimize the dose of ethanol. Although blood levels were proportional to dose, none of these new dose groups provided optimal blood levels. Congestive heart failure occurred in 1 other patient with previously asymptomatic cardiomyopathy. No other side effects were noted. Concomitant thrombolytic therapy was given in 8 patients, 1 of whom died of intracerebral hemorrhage. CONCLUSIONS: Caffeinol alone or combined with intravenous tissue plasminogen activator can be administered safely. Caffeine 8 mg/kg plus ethanol 0.4 g/kg produces target caffeine and ethanol levels of 8 to 10 microg/mL and 30 to 50 mg/dL, respectively. A randomized, placebo-controlled trial is needed to determine the neuroprotective effect of this combination. Stroke Program, Department of Neurology, University of Texas, Houston Medical School, USA. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=12690224
- Aronowski J, Strong R, Shirzadi A and Grotta JC (2003). Ethanol plus caffeine (caffeinol) for treatment of ischemic stroke: preclinical experience. Stroke 34: 1246-51. BACKGROUND AND PURPOSE: Ethanol and caffeine are 2 common psychoactive dietary components. We have recently shown that low-dose ethanol plus caffeine results in a 70% to 80% reduction of infarct volume after reversible common carotid/middle cerebral artery (CCA/MCA) occlusion in rats. The combination (caffeinol) was effective after either oral pretreatment or intravenous administration starting up to 2 hours after stroke onset. Ethanol alone aggravated ischemic damage, while caffeine alone was without effect. Daily caffeinol for 2 weeks before ischemia eliminated the neuroprotection seen with acute treatment (tolerance). The purpose of our present study was to further characterize the properties of caffeinol as a possible treatment for ischemic stroke. METHODS: The transient CCA/MCA occlusion model was used in all experiments. Five sets of experiments were conducted (1) to test the effectiveness of various doses of ethanol (0.2 to 0.65 g/kg) and caffeine (3 to 10 mg/kg) in the caffeinol mixture; (2) to test whether the neuroprotective dose of caffeinol can improve behavioral dysfunction; (3) to test whether chronic ethanol or caffeine before ischemia will affect efficacy of caffeinol treatment; (4) to test whether the protective effect of caffeinol can be improved by pairing it with 35 degrees C hypothermia; and (5) to test whether caffeinol affects frequency of hemorrhage after administration of recombinant tissue plasminogen activator (rtPA) in ischemic animals. RESULTS: Doses as low as 0.2 g/kg of ethanol and 6 mg/kg of caffeine in the caffeinol were effective in reducing cortical infarct volume and behavioral dysfunction after transient CCA/MCA occlusion. Daily exposure to ethanol but not caffeine before CCA/MCA occlusion eliminated the therapeutic efficacy of acute caffeinol treatment, similar to the tolerance observed after chronic exposure to caffeinol. The therapeutic effect of caffeinol could be further improved by pairing it with mild intraischemic hypothermia, and caffeinol did not increase hemorrhagic infarction when given in combination with rtPA. CONCLUSIONS: Low doses of caffeinol, equivalent to no more than 2 to 3 cups of strong coffee and 1 cocktail, are consistently and highly neuroprotective, are well tolerated, can be added to other therapies to increase the effect of each, and do not interfere with or complicate rtPA therapy. Caffeinol is an appropriate candidate for clinical trial in stroke patients, although it may be less effective in patients with regular alcohol intake. Stroke Program, Department of Neurology, University of Texas at Houston Medical School, Houston, 77030, USA. J.Aronowski@uth.tmc.edu http://www.ncbi.nlm.nih.gov/entrez/q..._uids=12690223
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