The Half Life of Caffeine

The Half Life of Caffeine

half-life-of-caffeineHow long will caffeine be in my system?

Caffeine has become the hot-topic of the moment.  Its addition to so many products makes it important to know how long caffeine sticks around in the body in order to prevent possible overdose.

Caffeine takes a certain amount of time to work through your system. One study some years ago showed that the half-life of caffeine in healthy adults is 5.7 hours (see source). This means if you consume 200mg of caffeine at mid-day, you would still have 100mg in you at around 5.45pm.

What factors can delay caffeine’s half life?

The same study mentioned above showed that people with compromised liver function had a significantly longer half-life (a 49-year-old woman having alcoholic hepatic disease had a serum half-life of 168 hours).

Others can have genetic factors influencing the gene responsible for caffeine metabolism. The gene CYP1A2 is needed by the liver break down up to 95% of the caffeine in the body. Other genes can influence how well this gene does its job (src).

Some people may lack the gene or the gene may be defective. In this case, caffeine stays in the body a long time, increases sensitivity to caffeine, and can even cause allergy-like symptoms.

variation of the gene PDSS2 also affects speed of metabolism. Those with the variation need a lot less caffeine to feel the stimulant affects.

Another study looked at how grapefruit juice may slow down caffeine metabolism in the liver, but it only was a slight inhibitor and wasn’t enough to cause warning.

What is the safe limit of caffeine in the body?

With caffeine levels in beverages and food continuing to climb – many people are asking – what exactly is the safe  limit?

While the average caffeine consumption is around 200mg per day, The Mayo Clinic recommends that people not exceed to 500-600mg per day. Consuming more than this can result in adverse overdose symtoms. This of course is affected by body weight, health, and individual sensitivity.

People can build up a tolerance to the effects of caffeine requiring larger doses to produce the same desired effect. If you are unsure of how much you can handle, it is best to start small and gradually increase your caffeine consumption as needed. Sometimes a caffeine detox is needed to reset caffeine tolerance back to safer/normal amounts.

Those who have built up a high caffeine tolerance can have severe caffeine withdrawal symptoms when detoxing, so it may be wise to quit caffeine gradually.

A lethal dose of caffeine (LD50) consumed orally is equivalent to 150 milligrams per kilogram of body weight, which is what we base our Death by Caffeine application on.

In conclusion, the half life of caffeine might be around 6 hours, but can be influenced by other factors. Caffeine is a drug and should be used with discretion as well as respected.

LONG TERM CAFFEINE USE WORSENS ALZHEIMER’S SYMPTOMS

Salt and protein to sleep and blame ‘Food Coma’ on the brain

I consumed Trader Joe’s chocolate cake for 4 servings last night with 28 grams of sugar which woke me up from 12 midnight to 3 am. Salt and protein has an effect on the brain to go back to sleep as described in this fruit fly study and one author’s regimen of combo of salt and sugar under the tongue. Caffeine in chocolate is negligible to have an effect but might have stronger effect on others.

Connie

In the book Eat for Heat, researcher Matt Stone describes this trick we mentioned above as a solution to help you sleep better.

“The mix of salt and sugar is absolutely necessary for stressful situations during the night. When insomnia occurs between 2 am and 4 am accompanied by a feeling of excess adrenaline flowing through your body (adrenaline spikes during this time), salt and sugar under the tongue is the only way forward.”

Blame ‘Food Coma’ On The Brain

Summary: Researchers investigate fruit fly brains to discover the connection between eating, sleep and activity.

Source: Bowling Green State University.

The humble fruit fly has proved to be a fruitful research subject for BGSU neuroscientist Dr. Robert Huber and colleagues from Scripps Research Institute in Florida and elsewhere. The collaborators’ research into their behavior has helped expand our understanding of some important neurobiological connections between eating and sleep — including the infamous “food coma” felt after a big meal.

The Scripps study was one of Huber’s projects as a fellow at the Radcliffe Institute for Advanced Studies at Harvard University in Cambridge, Mass., last year. As an expert in computational ethology, he uses computer technology to obtain meaningful numbers from complex systems — in this case, capturing and precisely recording the tiny Drosophilas’ behavior related to eating, activity levels and sleep.

The cause of the food coma turned out to be protein and salt, along with the time of day the food was consumed. Surprisingly, sugar did not seem to play a role, according to the study. The results of the experiments Huber conducted with lead researcher Dr. William Ja of Scripps and his team were reported in more than 200 newspapers around the world.

The scientists will now look more deeply at the brain structures that induce the insects to sleep after consuming protein and salt, and test theories about why sleep then would be beneficial.

“Clearly, protein is a very expensive commodity,” Huber said. “If sleep increases your ability to resorb it, that would be a possible reason. And the same thing with salt.” Carbohydrates, on the other hand, are much easier to come by in nature, he said, so might not call for such dedicated digestion.

The fruit flies’ preference for protein does explain their attraction to overripe fruit, where they can lay their eggs.

“The flies have very good sensory receptors to detect all kinds of volatile compounds that indicate ripe fruit and yeast,” Huber said.

Huber’s interest in computer ethology is tied to his fascination with the connection between genetics and behavior, first discovered and explored by the late molecular biologist Seymour Benzer, with whom Ja conducted postdoctoral research. Huber has also been working with other labs on projects utilizing video tracking and had an article in the journal PLoS One in 2012 about developing better technology to look at the activity patterns of fruit flies. His primary projects as a Radcliffe fellow are with Dr. Ed Kravitz of Harvard Medical School, examining addiction and aggression in Drosophila.

A shared interest in behavioral genetics is what also drew Huber to the Ja team’s work.

“Ja has always been interested in the connection between behavior and genetics,” Huber said. “And their lab is just phenomenal. The real advantage of the fruit flies is you have such exquisite control over all the different bits of their genes and there’s so much you can do with them.

“You can express a certain gene in a certain subtype of neurons. Mushroom bodies (a pair of brain structures having to do with learning and memory) have dopaminergic neurons only to do with short-term memory and others for long-term memory. You can put those specific neurons under the control of optigenetics by expressing a membrane channel, related to a photoreceptor. So when you shine a red light onto the fly’s head it opens up channels which specifically activate the entire subset of neurons for long-term memory, for instance. There’s no other model system where you can gain that level of control.”

Huber’s expertise with video tracking and applying computer vision to monitor and measure the tiny flies’ behavior allowed the researchers to collect much more reliable data “than having an observer there with a clipboard, writing a summary of what happens,” he said. “Instead, we apply computer technology with strict rules to objectively remove observer bias. Behavior is a very complex type of trait or phenotype, so it’s not as simple as measuring the height of something. We use computer technology with video tracking, integrating it with sensors and robotic interfaces. We can create automated learning paradigms in real time.”

Thus, a system devised by Huber senses when a fruit fly alights on a tiny platform and reaches up to eat from a tube. The computer measures exactly the number and duration of instances of feeding along with a record of the fly’s activity levels, including those that denote sleep.

“We can really improve our characterization of food consumption and activity,” Huber said. “In one second, we can get a thousand data points, very accurately, showing when, how much, how often they feed. That’s not something you are able to do by hand.”

During the food coma, the flies remain still for a certain amount of time and they are much less responsive to any kind of other cues than they would normally be, he said.

“There’s clearly something very potent about sleep itself,” Huber said. Using genetic manipulation techniques, the team will look at whether a neuron with a receptor for a neuropeptide called leucokinin is actually playing a role in causing the flies to fall asleep specifically after consuming protein and salt.

“You can turn those receptors on and off with molecular genetics and piece together how the whole network that controls sleep is put together,” Huber said.

This should help reveal more about the mechanics of sleeping and eating. Using a tiny but extremely powerful LED light, he is able to trigger responses in the genetically modified flies. When the light is not activated, the insects behave just like any other normal fruit fly.

Huber is also eager to explore the potential of the video tracking technology for “tying together metabolic physiology and how much animals eat, what they eat, and how they convert that into energy, and what that has to do with aging,” he said, noting that appetite and satiety, sleep patterns, aging and other functions are all controlled by neurosignals. Anything that interferes with one signal will affect something else. Another of his related projects is with Dr. Leslie Griffith at Brandeis University, regarding food choices, activity patterns and “clock genes.”

After spending several months observing the fruit flies up close, Huber said he has a new appreciation for them.

“They’re very intricate little ‘critters,’” he said. “I spent quite a few days at first just watching them, and their behavior is a lot more complex than what we might think. I did not appreciate them before going there.

a fruit fly.

“Flies are very good at learning,” he added. Additional research into those individuals who are not good at it has identified which genes are altered in these “behavioral mutants.” In collaboration with BGSU colleagues Drs. Moira van Staaden, biological sciences, and Jon Sprague, director of the Ohio Attorney General’s Center for the Future of Forensic Science, he plans to study the role these genes play as flies learn sensory cues paired with human drugs of abuse.

Following his return from Boston, Huber described his sabbatical as “phenomenal, I got to work with a whole group of scholars on so many interesting projects; it was so stimulating.” And having open access to “maker spaces” in Cambridge’s Central Square, halfway between Harvard and MIT, he created his very tiny electronic devices for improving precision — “I was like a kid in the candy store. I’m still very excited about it.”

The fruit flies have inspired not only scientific but also art projects. Huber is collaborating on a “fruit fly soundscape” that arose from his new friendship with Radcliffe fellow Reiko Yamada. A sound artist, classical pianist, experimental composer and now artist in residence at the Institute for Electronic and Acoustic Music at the University of Music and Performing Arts in Graz, Austria, Yamada was “really mesmerized by the difference in scale we live in between the fruit flies and humans,” Huber said. Their interactive soundscape will debut at the IEM Cube at the end of March.

In addition, Huber is collaborating with his former adviser Dr. Kent Rylander, now turned jazz musician since his retirement from Texas Tech University 15 years ago. Huber and Rylander are pursuing a project on the aesthetics, compositional patterns and improvisation of birdsong.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Source: Bowling Green State University 
Image Source: NeuroscienceNews.com image is credited to Mr.checker and is licensed CC BY SA 3.0.
Original Research: Full open access research for “Postprandial sleep mechanics in Drosophila” by Keith R Murphy, Sonali A Deshpande, Maria E Yurgel, James P Quinn, Jennifer L Weissbach, Alex C Keene, Ken Dawson-Scully, Robert Huber, Seth M Tomchik, and William W Ja in eLife. Published online November 22 2016 doi:10.7554/eLife.19334

CITE THIS NEUROSCIENCENEWS.COM ARTICLE
Bowling Green State University “Blame ‘Food Coma’ On The Brain.” NeuroscienceNews. NeuroscienceNews, 9 January 2017.
<http://neurosciencenews.com/food-coma-neuroscience-5899/&gt;.

Abstract

Postprandial sleep mechanics in Drosophila

Food consumption is thought to induce sleepiness. However, little is known about how postprandial sleep is regulated. Here, we simultaneously measured sleep and food intake of individual flies and found a transient rise in sleep following meals. Depending on the amount consumed, the effect ranged from slightly arousing to strongly sleep inducing. Postprandial sleep was positively correlated with ingested volume, protein, and salt—but not sucrose—revealing meal property-specific regulation. Silencing of leucokinin receptor (Lkr) neurons specifically reduced sleep induced by protein consumption. Thermogenetic stimulation of leucokinin (Lk) neurons decreased whereas Lk downregulation by RNAi increased postprandial sleep, suggestive of an inhibitory connection in the Lk-Lkr circuit. We further identified a subset of non-leucokininergic cells proximal to Lkr neurons that rhythmically increased postprandial sleep when silenced, suggesting that these cells are cyclically gated inhibitory inputs to Lkr neurons. Together, these findings reveal the dynamic nature of postprandial sleep.

“Postprandial sleep mechanics in Drosophila” by Keith R Murphy, Sonali A Deshpande, Maria E Yurgel, James P Quinn, Jennifer L Weissbach, Alex C Keene, Ken Dawson-Scully, Robert Huber, Seth M Tomchik, and William W Ja in eLife. Published online November 22 2016 doi:10.7554/eLife.19334

Cumulative lifetime stress may accelerate epigenetic aging

Cumulative lifetime stress may accelerate epigenetic aging

Cumulative lifetime stress may accelerate epigenetic aging, an effect that could be driven by glucocorticoid-induced epigenetic changes.

Background:

Chronic psychological stress is associated with accelerated aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear.

Results: We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock.
After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an urban, African American cohort (n = 392). This effect was primarily driven by personal life stressors, was more pronounced with advancing age, and was blunted in individuals with higher childhood abuse exposure.

Hypothesizing that these epigenetic effects could be mediated by glucocorticoid signaling, we found that a high number (n = 85) of epigenetic clock CpG sites were located within glucocorticoid response elements.

We further examined the functional effects of glucocorticoids on epigenetic clock CpGs in an independent sample with genome-wide DNA methylation (n = 124) and gene expression data (n = 297) before and after exposure to the glucocorticoid receptor
agonist dexamethasone.

Dexamethasone induced dynamic changes in methylation in 31.2 % (110/353) of these
CpGs and transcription in 81.7 % (139/170) of genes neighboring epigenetic clock CpGs. Disease enrichment analysis of these dexamethasone-regulated genes showed enriched association for aging-related diseases, including coronary artery disease, arteriosclerosis, and leukemias.

These findings contribute to our understanding of mechanisms linking
chronic stress with accelerated aging and heightened disease risk.

https://genomebiology.biomedcentral.com/track/pdf/10.1186/s13059-015-0828-5?site=http://genomebiology.biomedcentral.com

Membrane glucocorticoid receptors (mGRs) are a group of receptors which bind and are activated by glucocorticoids such as cortisol and corticosterone, as well as certain exogenous glucocorticoids such as dexamethasone.[1][2][3][4][5] Unlike the classical nuclear glucocorticoid receptor (GR), which mediates its effects via genomicmechanisms, mGRs are cell surface receptors which rapidly alter cell signaling via modulation of intracellular signaling cascades.[2][3] The identities of the mGRs have yet to be fully elucidated,[6] but are thought to include membrane-associated classical GRs[7][8] as well as yet-to-be-characterized G protein-coupled receptors(GPCRs).[1][4][9][10] Rapid effects of dexamethasone were found not be reversed by the GR antagonist mifepristone, indicating additional receptors besides just the classical GR.[11]

mGRs have been implicated in the rapid effects of glucocorticoids in the early central stress response[12][13] via modulating neuronal activity in the hypothalamushippocampusamygdala, and prefrontal cortex, among other areas.[7] In accordance, glucocorticoids are known to affect cognitionstress-adaptive behavior, and neuroendocrine output (e.g., suppression of oxytocin and vasopressin secretion)[4] within minutes.[7] mGRs appear to be partially involved in the anti-inflammatory and immunosuppressant effects of glucocorticoids.[3][5][14] mGRs are present in and appear to regulate many major bodily systems and organs, including the cardiovascularimmuneendocrine, and nervous systemssmooth and skeletal muscle, the liver, and fat tissue.[9] mGRs appear to cooperate with, complement, and synergize with classical nuclear GRs in various ways

 

Caffeine Level in Blood May Help Diagnose Parkinson’s

Caffeine Level in Blood May Help Diagnose Parkinson’s

Summary: A new study to be released in Neurology identifies caffeine levels in the blood as a potential biomarker for Parkinson’s disease, Researchers discovered people with Parkinson’s had lower levels of caffeine in their blood than people without the disease, even if they had consumed the same amount of caffeine.

Source: AAN.

Testing the level of caffeine in the blood may provide a simple way to aid the diagnosis of Parkinson’s disease, according to a study published in the January 3, 2018, online issue of Neurology.

The study found that people with Parkinson’s disease had significantly lower levels of caffeine in their blood than people without the disease, even if they consumed the same amount of caffeine.

“Previous studies have shown a link between caffeine and a lower risk of developing Parkinson’s disease, but we haven’t known much about how caffeine metabolizes within the people with the disease,” said study author Shinji Saiki, MD, PhD, of Juntendo University School of Medicine in Tokyo, Japan.

People in the study with more severe stages of the disease did not have lower levels of caffeine in the blood, suggesting that the decrease occurs from the earliest stages of the disease, according to David G. Munoz, MD, of the University of Toronto in Canada, who wrote an editorial accompanying the study.

“If these results can be confirmed, they would point to an easy test for early diagnosis of Parkinson’s, possibly even before symptoms are appearing,” Munoz said. “This is important because Parkinson’s disease is difficult to diagnose, especially at the early stages.”

The study involved 108 people who had Parkinson’s disease for an average of about six years and 31 people of the same age who did not have the disease. Their blood was tested for caffeine and for 11 byproducts the body makes as it metabolizes caffeine. They were also tested for mutations in genes that can affect caffeine metabolism.

The two groups consumed about the same amount of caffeine, with an average equivalent to about two cups of coffee per day. But the people with Parkinson’s disease had significantly lower blood levels of caffeine and nine of the 11 byproducts of caffeine in the blood. The caffeine level was an average of 79 picomoles per 10 microliters for people without Parkinson’s disease, compared to 24 picomoles per 10 microliters for people with the disease. For one of the byproducts, the level was below the amount that could be detected in more than 50 percent of the people with Parkinson’s disease.

caffeine model

In the statistical analysis, the researchers found that the test could be used to reliably identify the people with Parkinson’s disease, with a score of 0.98 where a score of 1 means that all cases are identified correctly.

In the genetic analysis, there were no differences in the caffeine-related genes between the two groups.

Limitations of the study include that people with severe Parkinson’s disease were not included, which could affect the ability to detect an association between disease severity and caffeine levels. Munoz also noted that all of the people with Parkinson’s were taking Parkinson’s medication and it’s possible that these drugs could affect the metabolism of caffeine.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: The study was supported by the Japan Agency for Medical Research and Development, Japan Society for the Promotion of Science, and the Japanese Ministry of Education, Culture, Sports, Science and Technology.

Source: Renee Tessman – AAN
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: The study will appear in Neurology.

Caffeine, drugs, iron, zinc, heart and latest research

Coffee is a complex mixture of chemicals that provides significant amounts of chlorogenic acid and caffeine. Unfiltered coffee is a significant source of cafestol and kahweol, which are diterpenes that have been implicated in the cholesterol-raising
effects of coffee.

The results of epidemiological research suggest that coffee consumption may help prevent several chronic diseases, including type 2 DM,41 Parkinson’s disease69 and liver
disease.

Large prospective cohort studies in the Netherlands, US, Finland and Sweden have found coffee consumption to be associated with significant dose-dependent reductions in the risk of developing type 2 DM, although the mechanisms are
unclear.

Several large prospective cohort studies have found that caffeine consumption from coffee and other beverages is inversely associated with the risk of Parkinson’s disease in men and women who have never used postmenopausal estrogen.3,67,68

The results of animal studies suggest that the ability of caffeine to block adenosine A2A-receptors in the brain may play a role in this protective effect.

Epidemiological studies also suggest that coffee consumption is associated with decreased risk of hepatic injury, cirrhosis and hepatocellular carcinoma, although the
mechanisms are not clear.

Inverse associations between coffee consumption and colorectal cancer risk observed in case-control studies have not generally been confirmed in prospective cohort studies.

Coffee and Health A Review of Recent Human Research

Most prospective cohort studies have not found that coffee consumption is associated with significantly increased risk of CHD or stroke.

However, randomized controlled trials lasting up to 12 weeks have found that coffee consumption is associated with increases in several cardiovascular disease
risk factors, including blood pressure6 and plasma tHct.

At present, there is little evidence that coffee consumption increases the risk of cancer. Although most studies have not found coffee or caffeine consumption to be inversely associated with bone mineral density in women who consume adequate calcium, positive associations between caffeine consumption and hip fracture risk in three prospective cohort studies suggest that limiting coffee consumption to 3 cups/d (300 mg/d
of caffeine) may help prevent osteoporotic fractures in older adults.

Although epidemiological data on the effects of caffeine during pregnancy are conflicting, they raise concern regarding the potential for high intakes of coffee or caffeine to increase the risk of spontaneous abortion and impair fetal growth

Serious adverse effects from caffeine at the levels consumed from coffee are uncommon, but there is a potential for adverse interactions with a number of medications. Regular
consumers of coffee and other caffeinated beverages may experience withdrawal symptoms, particularly if caffeine cessation is abrupt.

Overall, there is little evidence of health risks and some evidence of health benefits for adults consuming moderate amounts of coffee (3–4 cups/d providing 300–400 mg/d
of caffeine). A review of the effects of caffeine on human health commissioned by Health Canada also concluded that moderate caffeine intakes up to 400 mg/d are not associated
with adverse health effects in healthy adults.

However, some groups, including people with hypertension and the elderly, may be more vulnerable to the adverse effects of caffeine. Currently available evidence suggests that it would be prudent for women who are pregnant, lactating, or planning to become pregnant to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine.

Caffeinated soft drinks are the principal source of caffeine in the diets of children and adolescents in the US, although coffee consumption increases somewhat during adolescence.

Limited data from short-term clinical trials suggest that daily caffeine intakes of 3 mg/kg of body weight or more may have adverse effects in children and adolescents.

men women caffeine 3men women caffeine 2men women caffeine 1men women caffeine