Can combining acetaminophen and caffeine cause liver damage. How much caffeine is safe to consume while taking Tylenol. Are there specific groups at higher risk when mixing these substances. What are the symptoms of acetaminophen-induced liver toxicity.

The Unexpected Interaction Between Acetaminophen and Caffeine

Recent research has shed light on a potentially harmful interaction between two commonly consumed substances: acetaminophen (the active ingredient in Tylenol) and caffeine. While many people regularly combine these substances without issue, a study published in the journal Chemical Research in Toxicology suggests that consuming large amounts of caffeine while taking acetaminophen could potentially lead to liver damage.

This discovery is particularly significant given the widespread use of acetaminophen as a painkiller in the United States and the ubiquity of caffeine in beverages and certain medications. The study, conducted by researchers at the University of Washington in Seattle, marks the first time scientists have reported a potentially harmful interaction between acetaminophen and caffeine.

The Science Behind the Interaction

The research team, led by chemist Sid Nelson, Ph.D., conducted experiments using E. coli bacteria genetically engineered to express a key human liver enzyme responsible for detoxifying many prescription and nonprescription drugs. Their findings revealed that caffeine tripled the amount of a toxic byproduct called N-acetyl-p-benzoquinone imine (NAPQI) produced by the enzyme while breaking down acetaminophen.

NAPQI is the same toxin responsible for liver damage and failure in known toxic alcohol-acetaminophen interactions. Previous studies by the same researchers demonstrated that high doses of caffeine could increase the severity of liver damage in rats with acetaminophen-induced liver damage, lending further support to their current findings.

Assessing the Risk: How Much is Too Much?

Is it necessary to completely avoid combining acetaminophen and caffeine? Not necessarily. Dr. Nelson emphasizes that people don’t have to stop taking acetaminophen or consuming caffeine products altogether. However, he advises monitoring intake more carefully when taking them together, especially for those who also consume alcohol.

It’s important to note that the bacteria in the study were exposed to “megadoses” of both acetaminophen and caffeine, far higher than most individuals would normally consume daily. While most people would need to consume unusually high levels of these compounds together to experience dangerous effects, the exact toxic threshold has not yet been determined.

Factors That May Increase Risk

• Consumption of alcohol
• Use of certain anti-epileptic medications (e.g., carbamazepine and phenobarbital)
• Taking St. John’s Wort supplement
• Regular use of medications combining acetaminophen and caffeine

These factors may boost the levels of enzymes that produce NAPQI, potentially increasing the risk of liver damage when acetaminophen and caffeine are combined.

The Role of Caffeine in Pain Relief Medications

Caffeine is often intentionally combined with acetaminophen in certain medications designed to treat conditions such as migraine headaches, menstrual discomfort, and arthritis. These combination drugs leverage caffeine’s ability to enhance the pain-relieving effects of acetaminophen.

Why is caffeine added to pain medications? Caffeine can help the body absorb acetaminophen more quickly and effectively, potentially providing faster relief. However, in light of this new research, consumers may need to be more cautious about their overall caffeine intake when using these combination medications.

Common Medications Combining Acetaminophen and Caffeine

1. Excedrin (acetaminophen, aspirin, and caffeine)
2. Midol (acetaminophen, caffeine, and pyrilamine maleate)
3. Anacin (aspirin and caffeine)
4. Various store-brand equivalents of these medications

Recognizing the Signs of Acetaminophen-Induced Liver Damage

Given the potential risks associated with combining acetaminophen and caffeine, it’s crucial to be aware of the symptoms of acetaminophen-induced liver toxicity. These symptoms may not appear immediately and can develop over several days.

What are the early signs of acetaminophen-induced liver damage? Initial symptoms may include:

• Nausea and vomiting
• Loss of appetite
• Abdominal pain, particularly in the upper right area
• Fatigue

As liver damage progresses, more severe symptoms may develop:

• Yellowing of the skin and whites of the eyes (jaundice)
• Confusion or disorientation
• Dark urine
• Pale stools
• Excessive sweating
• Bleeding easily

If you experience any of these symptoms after taking acetaminophen, especially in combination with caffeine or alcohol, seek medical attention immediately.

Safer Use of Acetaminophen: Best Practices

While the interaction between acetaminophen and caffeine requires further study, there are several best practices you can follow to use acetaminophen more safely:

1. Follow dosage instructions carefully
2. Be aware of acetaminophen in combination medications
3. Avoid alcohol when taking acetaminophen
4. Monitor caffeine intake, especially from energy drinks and strong coffee
5. Consult with a healthcare provider if you have concerns or pre-existing liver conditions

How can you track your acetaminophen intake effectively? Consider keeping a log of all medications you take, including over-the-counter drugs and supplements. This can help you avoid accidentally exceeding the recommended daily limit of acetaminophen, which is generally 4,000 mg for adults.

Alternative Pain Relief Options

For those concerned about the potential risks of combining acetaminophen and caffeine, there are several alternative pain relief options to consider:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen
• Topical pain relievers
• Physical therapy
• Acupuncture
• Heat or cold therapy
• Relaxation techniques such as meditation or deep breathing exercises

It’s important to note that each of these alternatives may have its own set of risks and potential side effects. Always consult with a healthcare provider before making significant changes to your pain management regimen.

The Future of Acetaminophen and Caffeine Research

The discovery of this potential interaction between acetaminophen and caffeine opens up new avenues for research in the field of pharmacology and toxicology. Dr. Nelson and his team are currently studying the mechanism by which this toxic interaction occurs and are considering human studies in the future.

What questions remain unanswered about this interaction? Some key areas for future research include:

• Determining the exact threshold at which the combination becomes dangerous
• Investigating potential genetic factors that may increase susceptibility to liver damage
• Exploring the long-term effects of regular, combined consumption of acetaminophen and caffeine
• Developing safer alternatives or protective measures for those who require both substances

As research in this area progresses, it may lead to updated guidelines for the use of acetaminophen and caffeine, both separately and in combination. It could also influence the development of new pain relief medications that avoid this potentially harmful interaction.

Staying Informed: The Importance of Health Literacy

This research underscores the importance of health literacy and staying informed about the medications and substances we consume regularly. Many people may be unaware of the potential risks associated with combining common substances like acetaminophen and caffeine.

How can you improve your health literacy? Consider these strategies:

1. Read medication labels carefully
2. Ask your healthcare provider or pharmacist questions about your medications
3. Stay updated on health news from reputable sources
4. Participate in health education programs
5. Use reliable online resources to research health topics

By staying informed and proactive about your health, you can make better decisions about medication use and lifestyle choices that may impact your well-being.

As research continues to uncover new interactions and potential risks associated with common substances, it’s crucial to approach our health with a mindset of continuous learning and adaptation. The acetaminophen-caffeine interaction serves as a reminder that even seemingly harmless combinations can have unexpected effects on our bodies.

While this research raises important questions about the safety of combining acetaminophen and caffeine, it’s essential to remember that these findings are preliminary and based on laboratory studies. More research, particularly human studies, will be necessary to fully understand the implications for everyday use.

In the meantime, the best approach is to be mindful of your acetaminophen and caffeine intake, follow dosage instructions carefully, and consult with healthcare professionals if you have concerns. By staying informed and making conscious decisions about our health, we can navigate the complex world of medications and supplements more safely and effectively.

Caffeine and acetaminophen don’t mix well

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Sep 27 2007

Consuming large amounts of caffeine while taking acetaminophen, one of the most widely used painkillers in the United States, could potentially cause liver damage, according to a preliminary laboratory study reported in the Oct. 15 print issue of ACS’ Chemical Research in Toxicology, a monthly journal.

The toxic interaction could occur not only from drinking caffeinated beverages while taking the painkiller but also from using large amounts of medications that intentionally combine caffeine and acetaminophen for the treatment of migraine headaches, menstrual discomfort and other conditions, the researchers say.

Health experts have warned for years that consuming excess alcohol while taking acetaminophen can trigger toxic interactions and cause liver damage and even death. However, this is the first time scientists have reported a potentially harmful interaction while taking the painkiller with caffeine, the researchers say.

While the studies are preliminary findings conducted in bacteria and laboratory animals, they suggest that consumers may want to limit caffeine intake — including energy drinks and strong coffee — while taking acetaminophen.

Chemist Sid Nelson, Ph.D., and colleagues, of the University of Washington in Seattle, tested the effects of acetaminophen and caffeine on E. coli bacteria genetically engineered to express a key human enzyme in the liver that detoxifies many prescription and nonprescription drugs. The researchers found that caffeine triples the amount of a toxic byproduct, N-acetyl-p-benzoquinone imine (NAPQI), that the enzyme produces while breaking down acetaminophen. This same toxin is responsible for liver damage and failure in toxic alcohol-acetaminophen interactions, they say.

In previous studies, the same researchers showed that high doses of caffeine can increase the severity of liver damage in rats with acetaminophen-induced liver damage, thus supporting the current finding.

“People should be informed about this potentially harmful interaction,” Nelson says. “The bottom line is that you don’t have to stop taking acetaminophen or stop taking caffeine products, but you do need to monitor your intake more carefully when taking them together, especially if you drink alcohol.”

Nelson points out that the bacteria used in the study were exposed to ‘megadoses’ of both acetaminophen and caffeine, much higher than most individuals would normally consume on a daily basis. Most people would similarly need to consume unusually high levels of these compounds together to have a dangerous effect, but the toxic threshold has not yet been determined, he says.

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Certain groups may be more vulnerable to the potentially toxic interaction than others, Nelson says. This includes people who take certain anti-epileptic medications, including carbamazepine and phenobarbital, and those who take St. John’s Wort, a popular herbal supplement. These products have been shown to boost levels of the enzyme that produces the toxic liver metabolite NAPQI, an effect that will likely be heightened when taking both acetaminophen and caffeine together, he says.

Likewise, people who drink a lot of alcohol may be at increased risk for the toxic interaction, Nelson says. That’s because alcohol can trigger the production of yet another liver enzyme that produces the liver toxin NAPQI. The risks are also higher for those who take large amounts of medications that combine both acetaminophen and caffeine, which are often used together as a remedy for migraine headaches, arthritis and other conditions.

The researchers are currently studying the mechanism by which this toxic interaction occurs and are considering human studies in the future, they say. The National Institutes of Health funded the initial animal and bacterial studies.

http://www.acs.org/

Posted in: Drug Trial News

Tags: Acetaminophen, Alcohol, Anti-Epileptic Drug, Arthritis, Bacteria, Caffeine, Coffee, Drugs, E. coli, Enzyme, Laboratory, Liver, Metabolite, Migraine, OCT, Painkiller, Research, Toxicology, Toxin

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Mixing large doses of both acetaminophen painkiller and caffeine may increase risk of liver damage

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• ACS

• Discover Chemistry

• News Releases

• 2007

• September

• Mixing large doses of both acetaminophen painkiller and caffeine may increase risk of liver damage

FOR IMMEDIATE RELEASE | September 26, 2007

WASHINGTON, Sept. 26 2007 — Consuming large amounts of caffeine while taking acetaminophen, one of the most widely used painkillers in the United States, could potentially cause liver damage, according to a preliminary laboratory study reported in the Oct. 15 print issue of ACS’ Chemical Research in Toxicology, a monthly journal. The toxic interaction could occur not only from drinking caffeinated beverages while taking the painkiller but also from using large amounts of medications that intentionally combine caffeine and acetaminophen for the treatment of migraine headaches, menstrual discomfort and other conditions, the researchers say.

Health experts have warned for years that consuming excess alcohol while taking acetaminophen can trigger toxic interactions and cause liver damage and even death. However, this is the first time scientists have reported a potentially harmful interaction while taking the painkiller with caffeine, the researchers say.

While the studies are preliminary findings conducted in bacteria and laboratory animals, they suggest that consumers may want to limit caffeine intake — including energy drinks and strong coffee — while taking acetaminophen.

Chemist Sid Nelson, Ph.D., and colleagues, of the University of Washington in Seattle, tested the effects of acetaminophen and caffeine on E. coli bacteria genetically engineered to express a key human enzyme in the liver that detoxifies many prescription and nonprescription drugs. The researchers found that caffeine triples the amount of a toxic byproduct, N-acetyl-p-benzoquinone imine (NAPQI), that the enzyme produces while breaking down acetaminophen. This same toxin is responsible for liver damage and failure in toxic alcohol-acetaminophen interactions, they say.

In previous studies, the same researchers showed that high doses of caffeine can increase the severity of liver damage in rats with acetaminophen-induced liver damage, thus supporting the current finding.

“People should be informed about this potentially harmful interaction,” Nelson says. “The bottom line is that you don’t have to stop taking acetaminophen or stop taking caffeine products, but you do need to monitor your intake more carefully when taking them together, especially if you drink alcohol. ”

Nelson points out that the bacteria used in the study were exposed to ‘megadoses’ of both acetaminophen and caffeine, much higher than most individuals would normally consume on a daily basis. Most people would similarly need to consume unusually high levels of these compounds together to have a dangerous effect, but the toxic threshold has not yet been determined, he says.

Certain groups may be more vulnerable to the potentially toxic interaction than others, Nelson says. This includes people who take certain anti-epileptic medications, including carbamazepine and phenobarbital, and those who take St. John’s Wort, a popular herbal supplement. These products have been shown to boost levels of the enzyme that produces the toxic liver metabolite NAPQI, an effect that will likely be heightened when taking both acetaminophen and caffeine together, he says.

Likewise, people who drink a lot of alcohol may be at increased risk for the toxic interaction, Nelson says. That’s because alcohol can trigger the production of yet another liver enzyme that produces the liver toxin NAPQI. The risks are also higher for those who take large amounts of medications that combine both acetaminophen and caffeine, which are often used together as a remedy for migraine headaches, arthritis and other conditions.

The researchers are currently studying the mechanism by which this toxic interaction occurs and are considering human studies in the future, they say. The National Institutes of Health funded the initial animal and bacterial studies.

— Mark T. Sampson

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202-872-4400

The most scandalous cases when firms recalled their products

• Stories

In the pursuit of revenue, corporations lose millions of dollars, and customers lose their lives.

April 23, 20202

Just this year, the US Consumer Product Safety Commission asked customers to stop buying Panasonic laptops because their batteries caught fire; IKEA lamps, because their metal frames shock people; lights for bicycles that ignited while under the driver’s seat . ..

Companies often try to protect their customers. But not always.

Tylenol 1982

In the summer of 1982, there were seven cases of poisoning in Chicago with Tylenol, then the most popular pain reliever in the United States at the time. The first victim was a 12-year-old girl. After drinking the pill, she dropped dead after a few seconds. It turned out that the tablet contained 65 mg of cyanide (lethal dose – 5 mg!). Similar incidents occurred over the next two days in different parts of the city.

As you might guess, panic seized the city: people threw away their supplies of Tylenol, and sales in stores fell to zero. The management of Johnson & Johnson took unprecedented measures: they recalled the entire drug from pharmacies and stores, and this, so you understand, is about $ 100 million. As it turned out, the manufacturers were not to blame for anything: an anonymous poisoner was operating in Chicago, who poured poison into medicine packages, and then returned them to store shelves.

Johnson & Johnson developed a new way of packaging Tylenol: now under the cap of the vial, the neck was hermetically sealed with foil. Today it is the standard for pharmaceuticals. Tylenol has managed to regain its place in the drug market.

Firestone and Ford Explorer tires, 2000

In 2000, a scandal erupted in the United States when it became public knowledge that Ford Explorer SUVs rolled over on the roads much more often than other cars. In this case, we are talking only about cars equipped with original Firestone tires. The situation was aggravated by the fact that, as it turned out, both companies – Ford and Firestone – were aware of what was happening since 1996 years old, but made every effort not to correct technical errors, but to hush up the matter.

The number of victims in the USA alone exceeded one thousand people. When the secret became clear, every more or less self-respecting newspaper in the United States hastened to write a devastating, revealing article, their total number exceeded 5 thousand. Ford’s sales decreased by 80%, the company lost about $3 billion. Firestone has withdrawn about 3 million tires from sale.

Both companies, instead of paying compensation to the victims and their families, hastened to blame each other and got bogged down in lawsuits and litigations, some of which have not been completed to this day.

Chinese milk formulas and milk, 2008

In June 2008, a “melamine scandal” broke out in the world: a high content of melamine was found in the dairy products of a number of Chinese manufacturers – a substance that is essentially non-toxic (at least not more than than table salt), but at ultra-high concentration leading to kidney stones. It is commonly used in mineral fertilizers and plastics. Manufacturers added it so that when measured, the protein level in milk seemed higher (the milk itself was diluted with water). Two companies — Mengniu Dairy Group and Yili Industrial Group — added melamine to their milk (regular and powdered), infant formula, chocolate bars, instant coffee and cookies. Among other things, milk was supplied to schools and kindergartens. By the time the decision was made to recall the products, six children had died.

As a result, the Chinese authorities decided to seize all spoiled products (most of them were exported to the countries of the Pacific region). Even chicken eggs had to be seized, as melamine was added to chicken feed. 19 people – entrepreneurs and civil servants – were punished (up to life imprisonment). Two entrepreneurs, Jang Yuzhong and Geng Jinping, were shot dead in 2009.

Text author:Semyon Shraik

Hangover – Alkoinfo.ee

Advise

One of the causes of a hangover, that is, alcohol withdrawal syndrome, is the substance acetaldehyde, which is formed in the body as a result of the conversion of ethanol.

A hangover signals that the body is fighting poison – it is, in fact, a mild form of alcohol poisoning.

Hangover symptoms appear when the blood alcohol level begins to drop to the body’s natural level, close to zero.

Why does a hangover occur?

• Drinking alcohol increases urine output and causes fluid loss. Drinking alcohol is often associated with sweating, vomiting, and diarrhea, which in turn remove water and electrolytes from the body. Fluid loss leads to thirst, weakness and dizziness.
• Alcohol irritates the stomach and intestines. The resulting inflammatory process can lead to abdominal pain, nausea, and vomiting.
• Alcohol also depletes the body of vitamins and minerals and lowers blood sugar, which in turn causes fatigue, weakness and mood swings.
• Acetaldehyde, formed as an intermediate in the breakdown of alcohol, can speed up the pulse and cause palpitations, as well as sweating, nausea, and vomiting.
• Alcohol, of course, can induce deep sleep, although in fact, with excessive use, the first phases of sleep that should precede deep sleep fall out. In addition, the phase of REM sleep is reduced. In the phase of REM sleep, among other things, there is a consolidation of what has been learned, the ordering of thoughts and memories, and when it is present, a person feels fresh and rested after waking up. Therefore, a person with a hangover feels tired, not getting enough sleep.
• Although no clear explanation for hangover headaches has been found, it is associated with brain chemistry and hormone imbalances, as well as vasodilation.

How to prevent a hangover?

The less you drink, the less chance of a hangover. The best way to completely avoid a hangover is to not drink at all. Other methods do not give any guarantee that there will be no torment the next day.

Never cross the low-risk limits when drinking. The Alcocalculator will help you keep track of your drinks. See also tips on how to stay within the limits of moderation when drinking alcohol at home or outside.

Be sure to eat your fill before drinking. Then alcohol will be absorbed more slowly, and you will get less drunk.

In order to feel better the next day, it is important to drink enough water in addition to alcohol. When you drink water, you drink less alcohol, and water helps reduce fluid loss. Drink a few large glasses of water before going to bed.

Drinks containing more impurities, usually dark in color – such as red wine, brandy and port – cause more severe hangovers.

Do not mix drinks of different types. This irritates the stomach and guarantees future torment.

How to relieve a hangover?

• Drinking plenty of fluids, preferably non-carbonated drinks, is required to compensate for lost fluids. Fresh juice will help replace lost vitamins.
• If you really need it, you can take painkillers, and in case of digestive problems, drugs that reduce the acidity of the stomach. There is an over-the-counter powder in pharmacies that is taken dissolved in water to restore electrolytes and fluids in the body.
• Eat something: for example, with the loss of potassium that accompanies fluid loss, bananas and kiwis help fight.
• Don’t get drunk – it will only delay problems. Take a break from alcohol. Wanting to drink in the morning to relieve a hangover means you’re having withdrawal symptoms, which could indicate excessive drinking or an alcohol use disorder (abuse or addiction).
• Take a multivitamin to replace the body’s essentials lost through alcohol.

Ten myths about hangovers

1. Hangovers are caused by dehydration

Dehydration is one of the causes of a hangover, but not the only one. In fact, with each unit of alcohol from the body, in addition to the amount drunk, an additional 100 ml of liquid is excreted. For example, if you drink five servings of beer, the body will lose another liter of fluid.

However, will two liters of water save you from a hangover? Obviously not. Coincident symptoms of dehydration and hangovers are thirst, weakness, and headache. Have you ever had such a hangover that you could not eat and spent the whole day on your knees in front of the toilet? Daylight is deadly harsh, and it is almost impossible to express at least one thought coherently? These symptoms are not related to dehydration, but to the toxic effects of alcohol.

2. Coffee or a cold shower helps with a hangover.

You had a little too much last night. In the morning, you put coffee on and jump into a cold shower to cheer yourself up. Both of these can give you the slightest boost, but they won’t cure a hangover. In fact, coffee can increase it, as it also removes fluid from the body. So replace your coffee with water – and especially if you’ve been throwing up, causing you to lose even more fluid.

3. Hangover helps

It is believed that the morning hangover relieves the hangover. But this is not true. Hangovers begin to form as the blood alcohol level drops, and symptoms peak when the blood alcohol level approaches zero. Getting drunk is just delaying the hangover. At some point, you willy-nilly have to sober up, and the hangover will still come. Instead of alcohol, drink water or a sports drink instead to restore fluid levels, electrolytes, and vitamins.

Morning hangovers are often a signal that you are at serious risk of having problems with excessive drinking. It is also one of the symptoms of alcohol addiction.

4. Eating at the end of a party eases hangovers

If only it were so! It would be great if after a rampant drinking you could eat a couple of large hamburgers and a bowl of french fries – and wake up the next morning in perfect order. Actually it is not.

Food can certainly help prevent hangovers, but you should eat before drinking. The best choice would be fatty foods that are slowly digested. If you drink alcohol on a full stomach, it will be absorbed into the blood more slowly, and the hangover the next day will be a little easier.

5. A hangover occurs only if you drink a lot. At the same time, in order to earn a hangover, it is not necessary to get drunk every time, for some, just one serving is enough for this. The occurrence of a hangover, among other things, is affected by your weight and gender. In addition, hangovers are more likely to occur in people, for example, those who suffer from migraines or take medications that affect liver enzymes.

6. Beer and wine are better than strong alcohol

Some people literally swear that beer and wine don’t cause such a bad hangover as hard liquor. In fact, you will get drunk and hangover from any alcoholic drink, since they all contain ethanol. And it doesn’t matter in what order you drink them.

In addition, it is useful to remember that:

• red wine contains tannins that cause headaches in some people;
• mixing different drinks irritates the stomach and may increase hangovers;
• Highly contaminated drinks, usually dark in color – such as red wine, brandy and port – cause more severe hangovers;
• If you start the evening with strong alcohol, you often quickly lose your moderation and end up drinking more than you intended.

7. Workout Helps

While exercising the next morning may relieve conscience, no research has so far confirmed that it helps alleviate the physical effects of drinking alcohol. You can only burn calories from alcohol. In addition, after drinking alcohol, your body is ruled by a lack of fluids and nutrients. When you exercise, you again lose fluid and essential substances, so the end result can be further deterioration of well-being, and in severe cases, even a health-threatening condition. With a lack of fluid, the thermoregulation of the body is disturbed, so that when playing sports in hot weather, you can easily overheat.

During a hangover, both reaction speed, eye-hand coordination, and balance are impaired, which will affect your athletic performance, which requires fast and accurate action.

8. Bedtime painkillers

When taken with alcohol, acetaminophen (known as the cold medicine Tylenol/Tylenol) can destroy the liver. Other pain relievers, such as aspirin, paracetamol, and ibuprofen, can irritate the stomach and cause bleeding when combined with alcohol.

Also, taking a painkiller in the evening won’t do you any good: it will only give you pain relief for a few hours, but you don’t feel any pain while you sleep. Take a pain reliever in the morning if necessary.

9. Women and men get hangovers the same way

In fact, women get hangovers more easily. Even if a woman is exactly the same weight as a man, she needs less alcohol to get drunk. The male body contains more water, which dilutes alcohol and helps to reduce its effects. The male body also produces more of the enzyme that breaks down alcohol.

10. Hangover is not a big problem

Hangover shows that the body is poisoned by excess alcohol. Heavy drinking affects the nervous system and brain chemistry, leading to headaches, drowsiness, and nausea. Your intestines are irritated and inflamed. Yes, in fact, you will recover quickly and may not be affected by suffering after a good party. But overdoing it with alcohol is always a risk. Too much alcohol can lead to alcohol poisoning, you may pass out, and breathing may be difficult. You may even die.