Top INDEX
• - Basics : Caffeine basics.
• - Article : Caffeine and metabolism.
• Comment: Coffee Increases Testosterone.
• Comment: Other effects of too much caffeine.
• Presents : What do we know about coffee and health?
• - Article : Caffeine and metabolism.
• .
• - Course : Caffeine and Health.
• - Review : Coffee, Caffeine, and Health Outcomes ....
• Textbook: Caffeine and Activation Theory, ...

Insight: Caffeine was introduced based on its ability to increase work stamina.

Insight: Caffeine also stimulates certain portions of the autonomic nervous system.

Insight: It can treat and prevent the premature infant breathing disorders ....

Insight: ... large quantities of vitamin C increase caffeine clearance.

Insight: The same amount of caffeine can .. affect two otherwise similar individuals differently ....

Insight: Coffee Increases Testosterone.

Insight: Caffeine interacts with some medications, incl thyroid medication, psychiatric and depression drugs ....

Insight: Caffeine potentially leads to some spinal bone loss in postmenopausal women ....

Insight: Low doses of caffeine (20-200 mg) have positive effects on mood, vigilance and energy.

Insight: Coffee, mainly regular coffee decreases mortality linked to injuries and accidents.

Insight: Coffee does not affect blood pressure but caffeine alone increases blood pressure.

Insight: Decaf is rather more effective on mortality than regular coffee, hence large role of polyphenols.

Insight: Coffee prevents type 2 diabetes: reproducible and powerful effect.

Insight: it prevents prediabetics from developing diabetes provided that the coffee is consumed black ...

Insight: Caffeine provides ... 46-71% reduction in risk of death from chronic liver disease.

Insight: Pregnancy (low birth weight, preterm birth, pregnancy loss) (+ 22-46%) at all levels of intake.

Insight: smoking stimulates caffeine clearance and almost doubles the rate of caffeine metabolism ..

-Focus-: Monographs on Toxins and Enhancers.

Basics : Caffeine basics. INDEX
https://en.wikipedia.org/wiki/Caffeine

Caffeine was introduced based on its ability to increase work stamina just like Adrenal or Amphetamines.

Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class.
... it reversibly blocks the action of adenosine on its receptor and consequently prevents the onset of drowsiness induced by adenosine.
Caffeine also stimulates certain portions of the autonomic nervous system.

Caffeine is a bitter, white crystalline purine, a methylxanthine alkaloid, and is chemically related to the adenine and guanine bases of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). It is found in the seeds, nuts, or leaves of a number of plants native to Africa, East Asia and South America, and helps to protect them against predator insects and to prevent germination of nearby seeds.

The most well-known source of caffeine is the coffee bean, a misnomer for the seed of Coffea plants.
Beverages containing caffeine are ingested to relieve or prevent drowsiness and to improve performance.
To make these drinks, caffeine is extracted by steeping the plant product in water, a process called infusion.
Caffeine-containing drinks, such as coffee, tea, and cola, are very popular; as of 2014, 85% of American adults consumed some form of caffeine daily, consuming 164 mg on average.

Caffeine can have both positive and negative health effects.
It can treat and prevent the premature infant breathing disorders bronchopulmonary dysplasia of prematurity and apnea of prematurity. Caffeine citrate is on the WHO Model List of Essential Medicines. It may confer a modest protective effect against some diseases, including Parkinson's disease.

Some people experience sleep disruption or anxiety if they consume caffeine, but others show little disturbance. Evidence of a risk during pregnancy is equivocal; some authorities recommend that pregnant women limit consumption to the equivalent of two cups of coffee per day or less.

Caffeine can produce a mild form of drug dependence – associated with withdrawal symptoms such as sleepiness, headache, and irritability – when an individual stops using caffeine after repeated daily intake.

Tolerance to the autonomic effects of increased blood pressure and heart rate, and increased urine output, develops with chronic use (i.e., these symptoms become less pronounced or do not occur following consistent use).

... large quantities of vitamin C increase caffeine clearance.

The flavonoid, quercetin, found widely in fruit and vegetables, affects the metabolism of caffeine and paraxanthine and mainly decreases the urinary excretion of the latter compound by 32%; it also changes the excretion of several other metabolites of caffeine.

Women’s health
During pregnancy, caffeine metabolism is reduced, particularly during the third trimester.
This is associated with a reduction in the activity of the main enzyme involved in caffeine metabolism, and a consequent increase in caffeine half-life. Caffeine metabolism returns to normal a few weeks after delivery. The European Food Safety Authority (EFSA) advises that pregnant women limit their caffeine intake to 200 mg from all sources. The use of oral contraceptives almost doubles caffeine half-life, mainly during the second half of the menstrual cycle (the luteal phase).

Alcohol intake
Alcohol has an inhibitory effect on CYP1A2 activity (the enzyme involved in caffeine clearance).
Alcohol intake of 50 g per day prolongs caffeine half-life by 72% and decreases caffeine clearance by 36%.
Caffeine does not modify the motor or psychological symptoms of alcoholic intoxication nor does it cancel out the negative effects of alcohol on driving abilities despite its effects on vigilance and reaction time.

Some medications
Caffeine pharmacokinetics may be modified by some medical drugs.
Therefore, when prescribing caffeine-containing medicine or medicines that interact with caffeine metabolism, healthcare professionals should consider whether dosage adjustments or specific advice on caffeine consumption are required.

Genetic variability
Genetics may play a role in determining whether a person experiences side effects from caffeine.

Genetic variability in caffeine receptors
ADORA2A polymorphism
Adenosine A2 receptors are key to the stimulating effect of caffeine.
Human studies have shown that polymorphisms of these receptors may have an effect on the body.
Research suggests that the probability of having the ADORA2A genotype decreases as habitual caffeine consumption increases, meaning that individuals with this genotype may be less sensitive to the effects of caffeine and therefore be more likely to choose caffeinated beverages. A 2012 study considered the variability in the effect of caffeine intake on blood pressure (BP), suggesting that the variability in the acute BP response to coffee may be partly explained by genetic polymorphisms of the adenosine A2A receptors and a2-adrenergic receptors.

A large consortium (PEGASUS) study combined data from five population-based case-control studies including 1,325 Parkinson’s Disease (PD) cases and 1,735 controls. The study reported that PD risk was inversely associated with two ADORA2 polymorphisms. The distribution of distinct genotypes of the adenosine A2A receptor gene (ADORA2A) differs between self-rated caffeine-sensitive individuals with reduced sleep quality, and caffeine-insensitive individuals. The same amount of caffeine can therefore affect two otherwise similar individuals differently, depending on their genetic make-up.

Genetic variability in metabolism – CYP1A2 polymorphism
A polymorphism of the gene coding for CYP1A2, the enzyme responsible for 95% of caffeine metabolism, may potentially divide the population into ‘slow’ and ‘fast’ caffeine metabolisers. A meta-analysis looked at the association between habitual coffee intake and CYP1A2 polymorphism that splits the population into fast caffeine metabolisers and slow caffeine metabolisers. The analysis showed an association between fast metabolisers and coffee consumption in males, individuals younger than 59 years, and Caucasians, but not in females, individuals older than 59 years, and Asians. This is the first study to identify a weak association between the fast caffeine metaboliser profile and coffee intake in the Asian population as well as the age and gender related variation. Further research will support our understanding.

Caffeine intakes
The ADORA2A genotype is associated with different amounts of caffeine intake.
Individuals with the ADORA2A 1976TT genotype are significantly more likely to consume less caffeine.
Since individual reactions to caffeine may differ according to genetic variability, individuals tend to only consume the amount of caffeine they feel comfortable with.

The European Food Safety Authority (EFSA) advises that daily caffeine intakes of up to 400 mg and single doses of up to 200 mg do not raise concerns when consumed as part of a health balanced diet4. 400 mg caffeine is equivalent to up to 5 cups of coffee per day, as part of a healthy balanced diet and an active lifestyle. EFSA recommends lower levels for pregnant women, who are advised to limit caffeine intake to 200 mg from all sources.

Comment: Coffee Increases Testosterone. INDEX
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2686145
Comment to:

Association of Coffee Drinking With Mortality
by Genetic Variation in Caffeine MetabolismFindings
From the UK Biobank July 2, 2018

by:
Coffee Increases Testosterone.
James Howard, bs | independent biologist
July 4, 2018

Coffee is known to increase testosterone.
("Testosterone Controls Human and Great Ape Lifespans;" at: LINK: http://anthropogeny.com/Human%20Lifespan%20Testosterone.html )

Comment: Other effects of too much caffeine. INDEX
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2686145
Comment to:

Association of Coffee Drinking With Mortality
by Genetic Variation in Caffeine MetabolismFindings
From the UK Biobank July 2, 2018

by:
Caffeine vs increased Mortality
Andrew Macko, Physician | RI Medical
July 13, 2018

Other effects of too much caffeine:

It increases anxiety and disrupts sleep patterns, leading to a vicious cycle of restless sleep, relying on caffeine to help with daytime fatigue, followed by more insomnia.

Caffeine interacts with some medications, including thyroid medication, psychiatric and depression drugs, the antibiotic Cipro and the heartburn drug Tagamet.

It increases blood sugar levels, making it harder for those with type 2 diabetes to manage their insulin, according to a number of studies; it also can slightly raise blood pressure. The amount of caffeine in a particular coffee drink depends on the brew and beverage size:

  (1 oz.) -- 40 - 75 mg --- Restaurant espresso 
  (8 oz.) -  27-173 mg --- Instant coffee
  (8 oz.) -  95-200 mg --- Typical brewed coffee 
(16 oz.) --- 100 mg --- McDonald's brewed coffee 
(16 oz.) --- 330 mg --- Starbucks brewed coffee 
 --- Source: Mayo Clinic

Caffeine potentially leads to some spinal bone loss in postmenopausal women, if they typically drink more than three cups, or 300 mg of caffeine, a day, but don't get enough calcium in their diet, says Linda Massey, emeritus professor of nutrition at Washington State University. An older woman should make sure she gets at least 800 mg of calcium daily — through food or supplements — to offset caffeine's effect on calcium, adds Bess Dawson-Hughes, M.D., director of the Bone Metabolism Laboratory at Tufts University in Boston.

Coffee itself can also lead to stomach upset. If you have problems with acid reflux or heartburn, then coffee and even tea might not be right for you.

And if you have high cholesterol and you don't want your coffee adding to the problem, you need to use a paper filter to trap the cafestol, a compound in coffee that raises LDL cholesterol levels.

Caffeine is a drug and every drug has its downfall.
So in my opinion I would need more evidence based medicine to prove that caffeine offers a benefit to decrease mortality.

Present: What do we know about coffee and health? INDEX
Physiology and pathology. --- A 56 slide presentation.
www.coffeeandhealth.org/2016--INSERM--seminar-coffee-and-health.pdf
Association Scientifique Internationale du Cafe (ASIC)
Astrid Nehlig, PhD --- President of ASIC
INSERM U 1129 --- Paris, Strasbourg, France

E (Effects) Index
• Effects: General aspects on coffee.
• - Chart: Components in roasted coffee

• Effects: Sources of Caffeine.
• - Chart: Different constituents of coffee.

• Effects: General effects of coffee and caffeine.
• Effects: Interindividual differences.
• Effects: How does caffeine act?
• Effects: Total antioxidant capacity of various drinks.
• Effects: How do antioxidants act?
• Effects: Effects of coffee/caffeine on vigilance, mood and performance.
• Effects: Effects of coffee/caffeine on headache/migraine.
• Effects: Effects of coffee/caffeine on sleep.
• Effects: Effects of coffee/caffeine on anxiety.
• Effects: Effects of coffee on the brain: Pathological conditions.
• Effects: Coffee/caffeine and Alzheimer’s disease (AD).
• Effects: Other health effects of coffee: mortality, in general.
• Effects: Coffee and mortality, accidents & vigilance.
• Effects: Effects of coffee on the cardiovascular system.
• Effects: Cardiovascular disease risk.
• Effects: Coffee, caffeine and arterial blood pressure.

  Coffee and type 2 diabetes -

• Effects: Coffee and mortality from diabetes.
• Effects: Degree of Risk / Benefit.
• Effects: Prevention.
• Effects: Modulation of the risk of developing type 2 diabetes.

  Coffee and Cancer.

• Effects: Coffee and metabolic syndrome.
• Effects: How does coffee act?
• Effects: Coffee and cancer -- Proposition 65
• Effects: Coffee and mortality linked to cancer.
• Effects: (1) -- Classification.
• Effects: (1) -- Coffee protects against cancer in some organs
• Effects: (2) -- Coffee has no effect on cancer of some organs.

  Limitations: observational vs interventional studies.

• Effects: Recent umbrella review (1)
• Effects: Recent umbrella review (2)
• Effects: Recent umbrella review (3)
• Effects: Effects of coffee on the digestive tract.
• Effects: Coffee, caffeine and pregnancy.
• Effects: Caffeine and sports.
• Effects: Conclusions.

Effects: General aspects on coffee. E Index

Coffee is the drink most often consumed after water: 255 kg per second, i.e. 8 million tons per year,

Coffee contains more than 1000 substances

Lipids: diterpenes (cafestol and kahweol): 1.4-3.2% in green coffee

Coffee contains also proteins, minerals (calcium, magnesium), and vitamins (mainly from the B group.

Effects: Sources of Caffeine. E Index

Low to moderate intake: 1-3 cups/day
High intake: over 5 cups/day

Effects: General effects of coffee and caffeine. E Index

Low to moderate intake (50-250 mg caffeine in one sitting
= 1 small to 2 large cups of coffee)

Positive effects:
• feeling of well-being,
• relaxation,
• good mood,
• energy,
• increased vigilance,
• better concentration

High to very high intake (400-800 mg caffeine in one sitting
= 4 to 8 large cups of coffee)

Negative effects:
• nervousness,
• anxiety,
• aggressiveness,
• insomnia,
• tachycardia,
• tremor

Effects: Interindividual differences. E Index
Cornelis et al. 2007, 2014; Nehlig 2018

Caffeine consumption and effects are influenced by the expression of some genes

Caffeine metabolism: half-life 2.5-4.5 hr

Influence of the variable expression of the gene coding for the enzyme metabolizing 95% of caffeine
(cytochrome P450 isozyme 1A2-CYP1A2)

Slow (54%) and rapid metabolizers (46%)

Spontaneous caffeine consumption
? Influence of diverse genetic variations (polymorphisms) of the adenosine A2A receptor (main cerebral target of caffeine)

Effects: How does caffeine act? E Index

Adenosine modulates brain excitability
Caffeine acts as an antagonist at adenosine receptors

Effects: Total antioxidant capacity of various drinks. E Index

130   Espresso 
110   Soluable Coffee 
095   Filtered Coffee 
027   Red Wine 
019   Green Tea 
011   Black Tea 
009   Orange Juice 
007   Apple Juice 
005   Beer 

Effects: How do antioxidants act? E Index

Effects: Effects of coffee/caffeine on vigilance, mood and performance. E Index

• Low doses of caffeine (20-200 mg) have positive effects on mood, vigilance and energy.

  • Improvement of self-confidence, concentration ability and efficacy in intellectual tasks.
    Effects mostly marked in situations of reduced vigilance.
    Improvement of visual perception, reaction time, car driving and driving sleepiness.

• The effects of caffeine on performance and memory are rather indirect.

Effects: Effects of coffee/caffeine on headache/migraine. E Index
Derry et al. 2012

Caffeine contained in coffee
• Decreases pain in headaches and migraines

Caffeine alone

• Can be found in analgesic medication
  
• Potentiates the analgesic properties of some drugs (aspirin, ibuprofen, paracetamol)
  
• a 130-mg caffeine dose provides significant adjuvant therapy when
  combined with aspirin or paracetamol/aspirin in a variety of pain states
• Advice: take the anti-pain pill with coffee rather than water

Effects: Effects of coffee/caffeine on sleep. E Index
Rétey et al. 2007

• Sleep is one of the functions most sensitive to coffee and caffeine effects.
  • 100-200 mg caffeine (1-2 cups of coffee) at bedtime.
  • Increase sleep latency and decrease sleep quality, mainly deep sleep while REM sleep is not affected.
  • This effect persists for 3-4 h, sometimes longer.
  The effect varies with subjects, it is linked to a polymorphism of the adenosine A2A receptor.

Effects: Effects of coffee/caffeine on anxiety. E Index
Alsene et al. 2003

• Coffee and caffeine can generate anxiety.
  • Usually only at very high doses, far above habitual consumption.
  • This effects may occur at lower doses in some sensitive individuals.
    (link with a polymorphism of the adenosine A2A receptor)
• This increased sensitivity may lead some subjects to spontaneously reduce their coffee consumption

Effects: Effects of coffee on the brain: Pathological conditions. E Index
Costa et al. 2010

• Coffee/caffeine and Parkinson’s disease (PD).
  Parkinson’s disease (PD) results from the degeneration of dopaminergic neurons
  in the substantia nigra and striatum: leads to motor disturbance.
  • Effect: dose-dependent
  • Effect: causal; direct link between caffeine intake and decreased probability
    of developing PD; already tested in a clinical trial.
  • Effect: less marked in women (hormonal treatment).
  
  
  

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  Effects: Coffee/caffeine and Alzheimer’s disease (AD). E Index
  

  • A recent meta-analysis found a 16% risk reduction of developing AD in consumers of 3-4 cups of coffee daily compared to non-consumers (Santos et al, 2010)

  • In animal models of AD, caffeine and antioxidants inhibit the deposition of ß-amyloïd peptide and Tau hyperphosphorylation and protect cognitive function.
    (Arendash et al. 2006, 2009; Laurent et al., 2014; Yan et al. 2001)

  • Points to clarify

    Limited database, prospective studies are needed.

    Mechanism of action unclear: both caffeine and antioxidants could act on symptoms.

Effects: Other health effects of coffee: mortality, in general. E Index
Freedman et al. 2012

• Decrease of mortality all causes similar with regular and decaf.

• Tendency to larger effects of coffee consumption in women compared to men.

Effects: Coffee and mortality, accidents & vigilance. E Index
Freedman et al. 2012

Coffee, mainly regular coffee decreases mortality linked to injuries and accidents;
decaf has no effects in men, a slight effect in women.

Could reflect the effects of coffee (caffeine) on vigilance and concentration.

Effects: Effects of coffee on the cardiovascular system. E Index
Freedman et al. 2012

Coffee reduces mortality due to heart disease and stroke, decaf is as effective as regular coffee, hence role of caffeine and polyphenols.

Effects: Cardiovascular disease risk. E Index
Ding et al, 2014

Non-linear reduction of cardiovascular disease risk, maximum for 3-5 cups daily; ---- significant for coronary heart disease and stroke.

No negative effect of higher dosages
Reduction of mortality.

Effects: Coffee, caffeine and arterial blood pressure. E Index
Noordzij et al. 2005; Uiterwaal et al. 2007; Mubarak et al. 2012; Xie et al. 2018

Coffee does not affect blood pressure but caffeine alone increases blood pressure.

Coffee consumption is inversely associated with risk of hypertension

Effects: Coffee and type 2 diabetes
Coffee and mortality from diabetes E Index
Freedman et al. 2012

Coffee reduces mortality due to type 2 diabetes and its complications.

Decaf is rather more effective on mortality than regular coffee, hence large role of polyphenols.

Effects: Coffee and type 2 diabetes. E Index
Carlstrom & Larsson, 2018

                     Overall risk:  29% decrease
Risk change for one cup: -6%

Effects: Coffee and type 2 diabetes - Prevention. E Index
Pimentel et al. 2009; van Dam et al. 2009; Psaltopoulou et al, 2010; Carlstrom & Larsson, 2018

Coffee prevents type 2 diabetes: reproducible and powerful effect..
• Negative association found in American, European and Asian populations.
• Dose-dependent relationship between risk reduction (20-40%) and
  ---- increasing consumption of coffee (3-7 cups/day).

• Observed in men and women, obese and non obese subjects.

• Decaf is as powerful as regular coffee, hence effect mostly mediated by the antioxidants contained in coffee.

Effects: Coffee and type 2 diabetes
- Modulation of the risk of developing type 2 diabetes. E Index
Muley et al., 2012; Bhupathiraju et al. 2014; Lee et al, 2016

• Addition of sugar to coffee reduces its protective potential.
• Filtered coffee > boiled coffee and decaf > regular.
• Effect more pronounced over 60 years of age.
• Changes over quite short periods (4 years) modify the risk.
• Every increase by one cup of coffee/day decreases the risk by 11% for the next 4 years.
• Every decrease by one cup of coffee/day increases the risk by 17% for the next 4 years.
• Daily consumption of 3-4 cups of coffee acts on the evolution of diabetes:
  
  ---- it prevents prediabetics from developing diabetes provided that the coffee is consumed black without sugar or cream.
  
  

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  Effects: Coffee and metabolic syndrome. E Index
  Grosso et al. 2014; Marventano et al, 2016

  • Metabolic syndrome is the conjunction of various problems in carbohydrate, lipid and vascular regulation associated to overweight.

  • These problems may induce in the long term type 2 diabetes and predispose to atherosclerosis and stroke.

  • Coffee consumption reduces by 25% the risk of metabolic syndrome
    • Reduces waist size.
    • Accumulation of abdominal fat.
    • Hypertension.
    • Concentration of triglycerides in blood.
  
  
  

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  Effects: How does coffee act? E Index
  Kim et al., 2013; Shin et al., 2013; Bonyanian et al., 2015; Mellbye et al., 2017

  • Effect of the antioxidants of coffee that act at various steps of glucose metabolism.
  • Thermogenic and anti-inflammatory effects; modulation of adenosine receptor signaling; microbiome content and diversity.

  • Potential role of the diterpene cafestol.
    • Increases insulin production.
    • Shows antidiabetic properties in mice.

  • Pathologies associated to diabetes.
    • Reduction of diabetic retinopathy in a rat model.
    • Decrease of the risk renal complications shown in Korean women.
    • Acceleration of wound healing.
    
    
    

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    Effects: Coffee and cancer. E Index
    Coffee and Proposition 65

    • Recent long-running legal case in California that just came out which
      ---- could result in ‘cancer warning’ labels on all coffee cups and packaging.
    • Linked to the presence of acrylamide in coffee which is formed during the roasting process.
    • Acrylamide is a carcinogen if administered alone in large amounts to rodents but coffee is a complex mixture of numerous compounds.
    • coffee is by far not the largest contributor to acrylamide intake from food.

    • This decision, if applied, could affect the whole coffee chain and contradicts real-world and clinical evidence.
    
    
    

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    Effects: Coffee and mortality linked to cancer. E Index
    Freedman et al. 2012

    No effect of coffee consumption on mortality related to cancer.
    
    46-71% reduction in risk of death from chronic liver disease.

    
    
    

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    Effects: Effects of coffee on cancer (1). E Index
    

    Recent reclassification of coffee by IARC (International Agency for Research on Cancer, 2016).

    Coffee has been considered as belonging to group 3: “not classifiable as to its carcinogenicity to humans”.

    
    
    

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    Effects: Effects of coffee on cancer (2). E Index
    Coffee protects against cancer in some organs

    3 to 4 cups / day : Liver

    ----- 4 cups / day : Breast

    3 to 4 cups / day : Prostate

    ----- 4 cups / day : Endometrium

    3 to 4 cups / day : Pancreas

    ----- 5 cups / day : Colon-rectum

    Directly on skin : Skin

    
    
    

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    Effects: Effects of coffee on cancer (2). E Index
    Coffee has no effect on cancer of some organs

    no reference : Bladder

    no reference : Kidney

    no reference : Larynx

    no reference : Oesophagus

    no reference : Stomach

    no reference : Lung

    
    
    

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    Effects: Limitations: observational vs interventional studies. E Index
    

    Recent umbrella review (Poole et al., 2017, BMJ)

    • Review of evidence of observational and interventional. meta-analyses of studies on coffee consumption and health outcomes.

    • Compiled only meta-analyses on coffee and health.
      • Observational: 201
      • Interventional: 17
    
    
    

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    Effects: Limitations: observational vs interventional studies. E Index
    

    Recent umbrella review (Poole et al., 2017, BMJ) (2)

    • All cause mortality (-17%).
    • Cardiovascular mortality (- 19%).
    • Cardiovascular disease (- 15%).
    • Incident cancer and specific cancers (- 18%).
    • Neurological, metabolic and liver conditions.
  • Harmfull associations nullified by adjustement for smoking.
    
    
  • Potential negative effects of coffee consumption.
    • Pregnancy (low birth weight, preterm birth, pregnancy loss) (+ 22-46%) at all levels of intake.
    • Risk of fracture in women not in men (lack of vitamin D?).
  
  
  

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  Effects: Limitations: observational vs interventional studies. E Index
  

  Recent umbrella review
  (Poole et al., 2017, BMJ) (3)

  201 meta-analyses of observational vs 17 of interventional studies.

  Enormous lack of interventional studies allowing to analyze whether coffee is causal.

  
  
  

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  Effects: Effects of coffee on the digestive tract. E Index
  

  Coffee and digestion

  • Coffee
  • Increases the activity of hepatic enzymes.
  • Increases the frequency of gallbladder contractions.
  • Increases pancreatic secretion.
  • Increases the acid secretion of the stomach but only in individuals intolerant to coffee.

• On the other hand, coffee
  • Increases the acid secretion of the stomach but only in individuals intolerant to coffee.
  • Does not influence the development gastro-duodenal ulcers, inhibits the formation of gallstones.

Effects: Coffee, caffeine and pregnancy. E Index
Nawrot et al. 2003; Signorello et al. 2004; Poole et al. 2017; Temple et al., 2017

• In pregnant women, caffeine consumption should not go over 200 mg/day (2 cups of coffee).

• Based on the most recent studies.
  • Coffee has no effect on: fertility, congenital malformations or postnatal development.
  • Coffee might increase the risk of: low birth weight, preterm delivery, pregnancy loss (= 300 mg).
  • Most often no negative effects at 200 mg/day, only seen at higher intakes.

• Consumption needs to be reduced towards the end of pregnancy:
  ---- the half-life of caffeine is prolonged during the 3rd trimester.
  ---- (10.5 h vs 2.5-4.5 h) and is very high in the fœtus (about 100 h).
  
  

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  Effects: Caffeine and sports. E Index
  

  • Moderate quantities of caffeine (3-6 mg/kg) have beneficial effects in numerous sports.
    • Endurance sports.
    • Sports with stop -start (team sports and rackets).
    • Sports implying sustained and intense activity (long distance swimming and running, rowing ...)
  • Direct effects of caffeine on isolated efforts implying force and power,
    ---- such as dumbbell lifting or sprinting are less clear.
  • Caffeine is also active in women (endurance, performance, team sports).
  • Coffee is active but less used than caffeine tablets, appreciated by marathon runners.
  
  
  

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  Effects: Conclusions. E Index
  

  • Coffee has rather beneficial effects on health.
    • Improves mood and performance.
    • Regulates vigilance but can disturb sleep.
    • Prevents age-related cognitive decline, mainly in women.
    • Prevents Parkinson’s and possibly Alzheimer’s disease, liver cancer and diseases as well as type 2 diabetes.
    • Is protective for the cardiovascular system.
    • Can be consumed in moderation during pregnancy.
    • Too high dosages might have deleterious effects.
  
  

  
  

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  Article: Caffeine and metabolism. INDEX
  https://www.coffeeandhealth.org/topic-overview/caffeine-and-metabolism/
  
  

  Factors including smoking status, liver disease, alcohol consumption, some medications, and diet may all influence caffeine’s effect on an individual, with data suggesting that genetics also play a critical role, not only in how an individual reacts to caffeine, but in determining how much coffee they are likely to drink in the first place.
  
  

  Caffeine in the body
  Following oral consumption, caffeine is absorbed into the blood and body tissues.
  Absorption is virtually complete about 45 minutes after ingestion.
  The peak plasma caffeine concentration is reached 15-120 minutes after ingestion.
  Caffeine has a half-life of approximately four hours, although this timescale may be reduced or extended in certain groups of individuals such as pregnant women, those who smoke and people with impaired liver function. Caffeine’s effects will last for several hours, depending on how quickly or slowly it is metabolised by the body. Caffeine absorption from food and beverages does not seem to depend on age, gender, genetic background, and disease or drugs, alcohol and nicotine consumption. Caffeine absorption from tea and coffee is similar.
  
  

  How the body metabolises caffeine
  Caffeine is primarily metabolised in the liver by cytochrome P450 enzymes, which are responsible for more than 90% of caffeine clearance. The enzyme responsible for metabolism of caffeine is coded for by the gene CYP1A2.

  The large variability of CYP1A2 activity influences the clearance of caffeine and may be affected by factors such as gender, race, genetic polymorphisms, disease, and exposure to inducers. Two studies have reported that regular intakes of caffeine for one week did not alter caffeine pharmacokinetics. However, a further study suggested that the daily consumption of at least 3 cups of coffee increased CYP1A2 activity.
  
  

  Caffeine, health and individual factors
  A number of individual, non-genetic factors can impact the way caffeine is metabolised and utilised in the body.

  Liver disease
  The liver is the main organ responsible for caffeine metabolism.
  A small number of studies have looked at the potential impact of certain types of liver disease including cirrhosis and hepatitis B or C, suggesting that they may cause a reduction of plasma clearance of caffeine in correlation with the severity of the disease.
  
  
  
  Smoking status
  Research suggests that smoking stimulates caffeine clearance, and almost doubles the rate of caffeine metabolism as a result of enzyme induction. Cessation of smoking reduces caffeine clearance and changes the pattern of caffeine metabolism back to normal.
  
  

  Diet
  A number of dietary factors may also affect caffeine metabolism.
  Grapefruit juice consumption decreases caffeine clearance by 23% and prolongs half-life by 31%. Consumption of broccoli and brassica vegetables in general and absorption of ....
  

  
  

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   : INDEX
  

  
  

  
  

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  Course: Caffeine and Health. INDEX
  https://www.pdresources.org/page/index/5/Courses
  by Judy Perkin, DrPH --- CE Credit: 1 Hour --- online Course --- USA $14.00
  Professional Development Resources, Inc.
  Course #10-96 --- 2016 --- 15 pages --- 12 posttest questions
  This course was developed by the Florida Academy of Nutrition and Dietetics
  for their Manual of Medical Nutrition Therapy to provide healthcare professionals with
  evidence-based, non-biased information on nutrition-related topics.
  Signup LINK: https://www.pdresources.org/signup
  
  

  Course Abstract
  Caffeine and Health is a 1-hour online continuing education (CE) course that analyzes the potential health benefits, as well as the negative side effects, of caffeine consumption on a variety of health conditions.

  Caffeine is a rapidly absorbed organic compound that acts as a stimulant in the human body.
  The average amount of caffeine consumed in the US is approximately 300 mg per person per day - the equivalent to between 2 and 4 cups of coffee - with coffee accounting for about 3/4ths of the caffeine that is consumed in the American diet. This is considered to be a moderate caffeine intake, which, according to many studies, can promote a variety of health benefits.

  But some studies claim otherwise, even suggesting that one or two cups of coffee a day may negatively impact our health. So, what are we to believe?

  This course will analyze the potential health benefits, as well as the negative side effects, of caffeine consumption on

  a variety of health conditions, including:
  • dementia
  • Alzheimer’s disease,
  • headache,
  • cancer,
  • Parkinson’s disease,
  • gallstones,
  • cardiovascular disease,
  • hypertension,
  • type 2 diabetes mellitus,
  • fibrocystic breast conditions,
  • premenstrual syndrome,
  • pregnancy and lactation,
  • osteoporosis,
  • athletic performance,
  • weight control.

  
  

  This online course provides instant access to the course materials (PDF download) and CE test.
  After enrolling, click on My Account and scroll down to My Active Courses.
  From here you’ll see links to download/print the course materials and take the CE test
  (you can print the test to mark your answers on it while reading the course document).

  Successful completion of the online CE test (80% required to pass, 3 chances to take)
  and course evaluation are required to earn a certificate of completion.
  

  
  

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  Review: Coffee, Caffeine, and Health Outcomes: An Umbrella Review. INDEX
  Annual Review of Nutrition --- Volume 37, 2017 -- August 2017 --- Grosso, pp 131-156 https://doi.org/10.1146/annurev-nutr-071816-064941
  Giuseppe Grosso, Justyna Godos, Fabio Galvano, and Edward L. Giovannucci
  
  

  Abstract
  To evaluate the associations between coffee and caffeine consumption and various health outcomes, we performed an umbrella review of the evidence from meta-analyses of observational studies and randomized controlled trials (RCTs). Of the 59 unique outcomes examined in the selected 112 meta-analyses of observational studies,

  coffee was associated with a probable decreased risk of

  breast, colorectal, colon, endometrial, and prostate cancers;
  cardiovascular disease and mortality;
  Parkinson's disease; and type-2 diabetes. (and)
  a rise in blood pressure. ...

  
  

  
  

  ---

  
  

  Textbook: Caffeine and Activation Theory, Effects on Health and Behavior INDEX
  https://doi.org/10.1201/9781420006568
  Edited ByBarry D. Smith, Uma Gupta, B.S. Gupta
  400 pgs --- 25 October 2006 --- ebook
  
  

  The virtually universal popularity of caffeine, together with concerns about its potential pathogenic effects, have made it one of the most extensively studied drugs in history. However, despite the massive scientific literature on this important substance, most reviews have either focused on limited areas of study or been produced in popular form.

  t has long been recognized that physiological arousal is a basic and important factor in health and behavior (Smith, Osborne, Mann, Jones, & White, 2004). So important are its effects that numerous theories have focused on the arousal concept in an ongoing series of attempts to explain its origins, substrates, and consequences. In 1951, Elizabeth Duffy published her classic ....
  
  

  Section I: Caffeine: The Drug.
  The Arousal Drug of Choice: Sources and Consumption of Caffeine.
  Pharmacological Properties and Neurophsysiological Effects of Caffeine.
  
  Section II: Cardiovascular Effects.
  Acute Cardiovascular Effects of Caffeine: Hemodynamics and Heart Function.
  The Multifactorial Model of Cardiovascular Pathology: 
  --- Is Caffeine Pathogenic in Coronary Heart Disease?
  
  Blood Pressure Effects of Dietary Caffeine Are a Risk for Cardiovascular Disease.
  Effects of Coffee and Caffeine Consumption on Serum Lipids and Lipoproteins.
  
  
  Section III: Menstrual and Reproductive Effects.
  Menstrual Endocrinology and Pathology: Caffeine, Physiology, and PMS.
  Effects of Caffeine Intake on Female Fertility: A Critical Review.
  
  Section IV: Mood and Performance and Psychopathology.
  Effects of Caffeine on Mood.
  Caffeine, Mood, and Performance: A Selective Review.
  
  Caffeine and Multicomponent Task Performance.
  Caffeinism: History, Clinical Features, Diagnosis, and Treatment.
  
  Section V: Green and Black Teas.
  Catechins and Caffeine in Tea: A Review of Health Risks and Benefits.
  
  Section VI: Integration and Conclusion.
  Caffeine, Physiology, Pathology, and Behavior.

  
  

  LINK: Taylor and Francis Group
  https://www.taylorfrancis.com/books/9781420006568

  
  

  LINK to INDEX page

  LINK to Empower, Maintain, & Repair YOUR Health

  INDEX
  

  
  

  Articles on the Internet are transitory. The publishers may remove them, change sites, change URLs, or change titles. For the purpose of maintaining an availability of these articles for myself and you, I have reprinted parts in the relevant monographs with authorship maintained, coding simplified for error-free loading and minimal file size, and a LINK to the original document. Identity trackers and advertising bots have been removed from the original bloated and manipulative coding. NOTHING in writing is absolute; don't treat human opinion, projection, and observation as an Idol. Doing so can kill you, or worse, have you impose abuse on others. I gathered and researched this data, mediated with the Grace of God through prayer as a benefit in my integrating discovered available digital information which would acquaint me with the overall content related to the health issues. I have found that God is ALWAYS available when we are Reverent in our Asking, open-minded in our Listening, and, Assertive in our Choice of Action. Doctors did not expect me to survive birth. In the past 25 years, medical and health "experts" have cautioned or directed me, more than 14 times, that I had little time left to live, or would die ... because THEY did not understand my challenges, were not motivated to professionally diagnose, or, chose to superstitiously recall as absolute previously flawed training. I am still alive beyond age 70. With the assistance of God, my Personality, the research and a lack of dismissiveness of a number of persons ... I have found resolution to numerous health challenges. This has enabled me to assist many others who had been abandoned, brainwashed, or traumatized. May my experience and successes also empower you. This is one document which you may find helpful as a BASIC introduction to maintaining and improving YOUR health.