Chapter 07 | Caffeine and You

7. Uniquely You: Set Point, Genes, and Half-Life

January 7, 2013 By Kate Heyhoe

One size does not fit all – especially with caffeine.

This chapter helps explain why some people can drink five cups of coffee a day, and others top off at one. And why coffee is habit-forming for some people, but others have no problem quitting their morning joe.

We’re not always sure how caffeine works, but one thing is clear: all sorts of variables impact how each individual metabolizes caffeine, and even these change throughout a lifetime.

Early caffeine studies often treated subjects the same, whether they were men or women, smokers, or old or young. But over the past decade, scientific research has been more rigorous, aided by tools like the human genome project, MRIs, and other advances. Some of this newfound knowledge explains the discrepancies in early research results, and at the same time, reinforces the need for more research.

Want to know why your caffeine experience is unique to you? Jump into the topics of tolerance, genetics, and caffeine’s half-life, as explained in the next three sections…

Caffeine Basics: Table of Contents

Your Habit: Set Point, Tolerance, Withdrawal

January 7, 2013 By Kate Heyhoe

When is caffeine too much of a good thing? The body knows. In most instances, we self-regulate our consumption before serious adverse reactions occur. Our bodies tell us how much we can handle, and we learn to stay within that limit. But over time, we become less sensitive to caffeine’s effects, so we gradually increase consumption, to a point. This response is known as tolerance – and it varies from person to person. (Tolerance happens with alcohol and other drugs too, not just caffeine.)

Your Daily Norm: The Self-Regulating Set Point

Think back to when you first started drinking coffee or tea, or even Coke or Pepsi. You probably started with a small amount of caffeine, say one cup, and gradually drank more until you found a daily “norm,” which may be two, three, or four cups, for instance. You may have even tried more, but scaled back to fewer cups. However much you consume, your daily norm is a measure of your set point – a level of preferred stimulation.

Leveling Off: How Tolerance Works

The brain likes balance. It’s equipped with mechanisms to keep neural activity steady. Caffeine revs up neural activity, so the brain attempts to dampen this frenzy.

Like a commander in battle, General Brain sends in neurochemical soldiers to hold down the fort. The result: you get less of a kick from caffeine. So you fight back with more caffeine, and up your consumption – until the point when General Brain and your caffeine habit reach detente. This balance becomes your set point.

In other words, when a drug’s effects are felt over long periods of time, our adaptive brain adjusts to its presence, and considers the effects to be part of normal brain function. When the drug is absent, you experience cravings. This is true of caffeine, amphetamines, nicotine, and even sugar.

Adapting to Your Personal Level of Caffeine

Think of your set point as your personal adaptation to caffeine. Your set point adjusts as your tolerance level changes. As mentioned, this is true of caffeine and other stimulants, like nicotine and alcohol, and even sugar. Some glucose, or dietary sugar, is essential to normal brain functioning. When the customary balance of sugar in the brain is out of sync, this can also create cravings.

So the absence of caffeine creates cravings in habitual users. And if your habit is to always take caffeine with sugar, your brain expects and craves both the caffeine and the sugar. A daily Frappucino may deliver a double-whammy of reward – and a double-edged craving if withheld. Does this sound familiar?

One school of thought suggests brain boost is really just a result of withdrawal. That is, a caffeine-dependent brain heads into withdrawal between doses (like overnight), and the next hit of caffeine merely jumps our brains back into balance.

There may be some truth to this theory, but it doesn’t explain why both one-time and habitual users experience the same caffeine boosts, at least for certain types of behavior.

For instance, caffeine’s enhancing effects on memory, reaction time, reasoning, mood, and attention span don’t appear to diminish with tolerance (or not severely). Energy-producing or ergogenic actions, like athletics, also happen with just a single one dose. Runners still get the same performance boost whether they’re habitual caffeine users or not.

Caffeine Withdrawal: Three Symptoms in 24 Hours

According to the American Psychiatric Association, caffeine withdrawal syndrome is diagnosed when three or more of these symptoms occur within 24 hours after stopping or reducing prolonged daily caffeine use:

headache
marked fatigue or drowsiness
dysphoric mood, depressed mood, or irritability
difficulty concentrating
flu-like symptoms, nausea, vomiting, or muscle pain/stiffness

Additionally, these symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. And, the symptoms are not associated with the direct physiological effects of another medical condition (e.g., migraine, viral illness) and are not better accounted for by another mental disorder.

To avoid these symptoms, experts say to taper off gradually over a few days to a week.

Withdrawal Syndrome and Resetting Your Set Point

If you notice you’re not getting the same kick from caffeine, try resetting your set point by weaning yourself off caffeine for a while. Let the brain and body revert to their natural caffeine-free state.

But if you are addicted and quit abruptly, you may feel symptoms of withdrawal – a classic indicator of physical dependence. Headaches top the list, along with fatigue, sleepiness, brain fog, bad moods, concentration difficulty, depression, flu-like symptoms, and all out crankiness. (Painkillers like Excedrin frequently contain caffeine, so taking them to ease a withdrawal headache is like downing a “hair of the dog” cocktail for a hangover.)

Withdrawal symptoms are why many people never succeed at quitting caffeine. They can’t get past the first 24 hours without ill effects, so they return to their habit. But with caffeine, withdrawal symptoms are minor and best overcome by tapering down on consumption.

Caffeine Intervention: My Personal Reset Plan

I practice a weekly plan to reset my caffeine tolerance level. On weekdays, I drink one cup of coffee, or 100 mg of caffeine (I’m a slow metabolizer, so this is my max). But on Sunday mornings, I switch to a cup of tea, about 25 mg of caffeine. Sometimes I go wild and have two cups of tea, but that’s still half of my normal caffeine regimen. Come Monday mornings, my usual coffee dose seems to have more punch to it. Who would have thought I’d enjoy Mondays all the more? Maybe it’s all in my head, but compared to non-reset weeks, I feel perkier, happier, and rarin’ to go. [Note: This strategy may not work for everyone, and it’s not intended as medical or health advice.]

Coming up: Caffeine’s half-life, or “How long does caffeine stay in my body?”…

Caffeine Basics: Table of Contents

Caffeine’s Complicated Half-Life

January 7, 2013 By Kate Heyhoe

Caffeine’s half-life is longer than cocaine’s

In the 1983 film The Big Chill, actress Glenn Close snorts cocaine, something she hasn’t done in decades. In the following scene, she’s sitting up in bed, fidgeting, rambling, and fully awake, while her husband sleeps soundly next to her. The next morning, he’s peppy and ready for a run, while she’s a wrung out rag of exhaustion.

Caffeine as a drug is a far cry from cocaine. But the two substances have one thing in common: they block sleep. In minutes, caffeine and cocaine turn on your “awake” switch – but shutting down and dozing off isn’t as quick or easy. It takes hours for both drugs to wear off.

The length of time a drug stays in the body is measured by its half-life; it’s the time it takes for half the substance to be eliminated from the system.

Cocaine’s half-life is short, about 90 minutes. Caffeine’s is about three times longer, but caffeine is a far less potent psychotropic drug. In either case, after the half-life moment is reached, the substance continues to churn in your system with diminishing impact, until completely eliminated.

My Buzz vs. Your Buzz

My sister-in-law DeAnn drinks iced tea all day. She carries a giant thermal cup of it wherever she goes, refilling frequently so the caffeine-well never runs dry. She has no problem falling asleep at night. But my brother John, her husband, practically buzzes on Sanka, which is 97 percent decaffeinated. He nurses a single refrigerated can of Coke throughout the day, taking a few sips now and then. Give him more caffeine than that, and he’s up all night, fidgeting like Glenn Close, after her cocaine blast in The Big Chill.

When my husband and I sit down for coffee, we each drink a cup a day, yet the caffeine churns longer in my body than his. Why? Because of multiple factors: I’m 100 pounds, a woman, and part Asian. He’s 160-pounds, a man, and Caucasian. Other genetic traits also make a difference.

Liver Enzymes Can Be Fickle

The liver metabolizes caffeine, using enzymes to break caffeine down into compounds (which are sent to the kidneys and expelled through urine). One particular enzyme, with the fetching name CYP1A2, metabolizes caffeine, as well as other substances.

When this enzyme is in large supply – and not particularly busy – caffeine gets processed and eliminated swiftly. But when the enzyme has a larger workload and is in demand by caffeine and other substances simultaneously, it gets spread thin (kind of like multi-tasking). As a result, the half-life for caffeine – or the other elements, or both – can last longer.

In other words, other substances can speed up or slow down the processing of caffeine in your body. What can compete with CYP1A2’s breakdown of caffeine? Drugs, including but not limited to antidepressants, cardio drugs like Lidocaine, and acetominophen (Tylenol), oral contraceptives, and plenty of others.

Some substances that help caffeine be more quickly processed and expelled include: tobacco smoke, grilled meats, and broccoli. Substances and conditions that slow down the processing of caffeine (so its effects last longer) include alcohol, pregnancy, liver disease, obesity, and possibly even grapefruit juice.

Half-Life Variables

Weight, body mass, sex, age, race, genes, liver function, concurrent medications, and other factors can influence how fast or slow each individual metabolizes caffeine.

So the half-life of caffeine isn’t a fixed number, and even experts disagree on a standard. In this book, I use 4 hours as the rule-of-thumb, but the half-life of caffeine in a healthy adult may range from 3 to 7.5 hours.

Here are some examples of how caffeine’s half-life can vary:

Asians metabolize caffeine more slowly than Causasians
Smokers metabolize caffeine 50 percent faster than nonsmokers; that is, it stays in their system for a shorter period of time (ever notice that smokers consume more coffee than nonsmokers?)
Alcohol reduces the time it takes to metabolize caffeine; drinkers feel caffeine’s effects longer
Liver disease makes caffeine more difficult to process; the half-life can last 96 hours in persons with severe liver disease
Oral contraceptives double the time it takes to metabolize caffeine; the half-life ranges from 5 to 10 hours
Pregnancy boosts the half-life of caffeine; caffeine’s half-life is 9 to 11 hours in pregnant women.
In infants and young children, the half-life is longer than in adults; caffeine’s half-life in a newborn may last 30 hours or more.
The larger the dose, the longer the half-life: Unlike other drugs, caffeine’s half-life is longer at higher doses. In other words, 600 mg of caffeine stays in the system as much as 3 hours longer that of a typical dose of 100-200 mg, which is around 4 hours in most people.

I’ve got more on women, babies and caffeine later in this book. But first, there’s an exciting insight into caffeine’s half-life, and it has to do with our genetic code.

Up next: The caffeine gene determines if you’re a fast metabolizer of caffeine, and it may predict heart attacks…

Caffeine Basics: Table of Contents

The Caffeine Gene and You

January 7, 2013 By Kate Heyhoe

In the old days, fortune-tellers read tea leaves, coffee grounds or palms to predict the future. Today, genetic testing companies reveal your personal mysteries, with scientific accuracy. They tell you who your child’s other parent is, who your own parents are, whether cancer runs in the family, or if the person who looks just like you on YouTube really is your long lost sibling. Get your genetic data now!

Here’s where things get interesting: There appears to be a big kernel of truth to the idea that your genes dictate how fast you metabolize caffeine. You can actually find out if you’re genetically programmed to crave large or small amounts of caffeine. All it takes is a simple cheek swab, sent to a genetic testing firm. So let’s jump straight to the actual research – which reveals that caffeine lingers longer when certain genes are switched on or off.

Clear as Mud Becomes Crystal Clearer (almost)

Caffeine researchers hit an “aha!” moment in 2010. They discovered that two genes determine whether you metabolize caffeine slowly or quickly. Together, these two genes are responsible for inherited differences in the way people process caffeine. They’re one reason why some people get amped from a single cup of coffee, while others down three cups before noon and another two at dinner, and never once jitter.

It’s in your genes, as the saying goes. Environmental factors, like whether you’re a smoker, still play a role. But genetic markers appear to explain a lot.

The two genes are known as CYP1A2, which has long been associated with caffeine (it produces an enzyme by the same name), and AHR, a gene that regulates the activity of CYP1A2. Researchers sifted through 300,000 genetic markers, before noticing that these two genes were essentially holding hands.

Slow and Fast Metabolizers

Every person has both of these genes, but CYP1A2 comes in two versions (or alleles; in this case differentiated by a single nucleotide). It’s like having a switch that is either turned on or off. This tiny variation makes you either a slow or fast metabolizer of caffeine ¬– it regulates how efficiently your liver breaks down and flushes caffeine from your system.

Slow metabolizers tend to drink less coffee (or other form of caffeine); fast metabolizers fuel up on more caffeine to keep feeling its effects. In one report, fast metabolizers averaged 40 mg more caffeine per day than did slow metabolizers.

In case you’re wondering, these particular caffeine genes don’t just regulate caffeine. They’re actually multi-taskers, and control other compounds, including ones related to certain cancers. (While we’re on the subject, different genes play a role in alcohol and nicotine addiction, too.)

The Caffeine Gene’s Split Personality

If you’re up for more complicated data: CYP1A2 also refers to an enzyme, generated by the gene CYP1A2 (genes are usually differentiated from their enzymes by italics). CYP is an abbreviation for a superfamily of enzymes and their encoding genes, known as cytochrome P450. The numbers and letters that follow CYP indicate the gene family, subfamily, and specific gene. Are your eyes glazing over yet? This may be too much information, but if you see CYP1A2 referenced as a both a gene and an enzyme, you’ll understand why.

Heart Attack Risk: What the Caffeine Gene Shows

One study based on 4,000 coffee drinkers used the CYP1A2 gene to identify slow and fast caffeine metabolizers, and their relationship to heart health. Slow metabolizers showed an increased risk of nonfatal heart attack. Women appeared to be at a slightly higher risk than men, probably because hormonal differences also slow caffeine’s breakdown in women.

For men and women, slow metabolizers showed increasing risk of nonfatal heart attack with increasing coffee consumption. Fast metabolizers, those who drank up to 3 cups a day, actually had a lower risk, as much as 52% lower.

So here’s the takeaway:

If you are a slow metabolizer, then drinking more than a cup of coffee a day may be risky for your heart. But a single cup of coffee seems to have no effect on heart risk, regardless of the genome variants. Moderation and self-regulation appear to be key.

Next Up: Are you addicted to caffeine? Chapter 8 looks at clinical caffeine disorders, including “The Starbucks Defense”…

Caffeine Basics: Table of Contents