Nearly 20% of the workforce worldwide work at times outside of 7 AM - 6 PM due to evening shifts, night shifts, or rotating shifts.1

Shift work has been connected to a higher prevalence in obesity, diabetes, metabolic disturbances, and cardiovascular morbidity.2

The increased health problems related to shift work are thought to be at least partially due to circadian misalignment that results in reduced insulin sensitivity, poorer glucose regulation and altered patterns of leptin and cortisol secretion.3

Sleep deprivation is also thought to be a contributor to the increased health problems seen among shift work populations, as shift workers often report greater sleep difficulties and reduced sleep quantity as compared to typical daytime employees.4 It's been well documented that sleep deprivation is an independent risk factor for many of the health detriments associated with shift work.5

Recent research has investigated the impact of delayed timing of eating on weight and metabolism. In a recent review of the evidence to date, scientists make a strong case that delayed timing of eating could be a contributing factor to weight gain and metabolic dysregulation.6

Weight Gain & Timing of Eating - Research Findings

Research on the impact of delayed timing of eating on weight and metabolism has provided the following insights:

- Delays in the typical daytime pattern of eating has been found to increase the risk of obesity and metabolic syndrome in humans.2,7

- Delayed sleep timing is associated with poorer diet and later eating times, the latter of which is related to higher BMI.8

- Evening type (owls) chronotype, as compared to the morning type (lark), has also been found to be associated with larger meals, later eating times, and higher BMI.9-11

- Descriptive studies of non-eating disordered adults found that breakfast intake was negatively related to total daily caloric intake and weight gain, 12,13 while the proportion of food consumed late at night was positively related to total energy intake.14

- One study found that distributing the majority of meals to the morning for 6 weeks resulted in greater weight loss compared to distributing the majority of meals to the afternoon and evening for 6 weeks.15

- Another study found that "late eaters" (those eating their large, mid-day meal after 3 PM), as compared to "early eaters" (eating their mid-day meal before 3 PM), lost significantly less weight during the 5-month study, despite similar self-reported energy intake, macronutrient content, estimated energy expenditure, appetitive hormone profiles, and self-reported sleep duration.16

Conclusion

Results from various studies collectively suggest that nighttime eating may contribute to weight gain, or, at a minimum, maintenance of increased weight.6

Based on this body of research, behavioral modification strategies that might promote weight loss or prevent weight gain include:

- Eating lunch earlier in the daytime 16

- Eliminating eating in the evening after 7-8 PM 8,17

- Avoiding sleep restriction when dieting 18

- Advancing bedtime 8

Implications for Shift Workers

While these new behavioral modification strategies are promising to individuals operating within a typical circadian rhythm, shift workers can face various challenges when implementing these strategies.

Given the unique challenges that shift workers face, health strategies such as timing of eating must be modified to best fit one’s schedule.

Shiftwork Lifestyle Training

Adjusting to a shiftwork lifestyle isn’t intuitive, and most shiftworkers don’t know how to adjust their lifestyle to minimize the negative effects of working around the clock. As a result, workers’ job performance, safety, health, and family life can suffer as company profits and productivity fall.

Training workers on how to manage a shiftwork lifestyle is a powerful tool for improving your employees’ physical and psychological well-being, thereby increasing morale and effectiveness, while potentially reducing health care costs.

CIRCADIAN® Managing a Shiftwork Lifestyle Training

Working closely with researchers and experienced shiftworkers, CIRCADIAN has developed the Managing a Shiftwork Lifestyle training program to provide practical solutions for easing the adjustment and day-to-day difficulties associated with shiftwork lifestyles.

Download our complementary CIRCADIAN® white paper, “Shiftwork Lifestyle Training: Employee and Employer Benefits”.

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About CIRCADIAN®

CIRCADIAN® is the global leader in providing 24/7 workforce performance and safety solutions for businesses that operate around the clock. Through a unique combination of consulting expertise, research and technology, software tools and informative publications, CIRCADIAN helps organizations in the 24-hour economy optimize employee performance and reduce the inherent risks and costs of their extended hours operations.

REFERENCES

1. Wright Jr KP, Bogan RK, Wyatt JK. Shift work and the assessment and management of shift work disorder (SWD). Sleep Med Rev. (2013): 17:41–54.

2. Åkerstedt T, Wright KP. Sleep loss and fatigue in shift work and shift work disorder. Sleep Med Clin. (2009): 4:257–71.

3. Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A. (2009): 106:4453–8.

4. Åkerstedt, Torbjörn. "Shift work and disturbed sleep/wakefulness." Occupational Medicine 53.2 (2003): 89-94.

5. Mullington, Janet M., et al. "Cardiovascular, inflammatory, and metabolic consequences of sleep deprivation." Progress in cardiovascular diseases 51.4 (2009): 294-302.

6. Allison, Kelly C., Namni Goel, and Rexford S. Ahima. "Delayed timing of eating: impact on weight and metabolism." Current Obesity Reports 3.1 (2014): 91-100.

7. Maury E, Ramsey KM, Bass J. Circadian rhythms and metabolic syndrome: from experimental genetics to human disease. Circ Res. (2010): 106:447–62.

8. Baron KG, Reid KJ, Kern AS, Zee PC. Role of sleep timing in caloric intake and BMI. Obesity. (2011): 19:1374–81.

9. Lucassen EA, Zhao X, Rother KI, Mattingly MS, Courville AB, de Jonge L, et al. Evening chronotype is associated with changes in eating behavior, more sleep apnea, and increased stress hormones in short sleeping obese individuals. PLoS One. (2013): 8:e56519.

10. Kanerva N, Kronholm E, Partonen T, Ovaskainen ML, Kaartinen NE, Konttinen H, et al. Tendency toward eveningness is associated with unhealthy dietary habits. Chronobiol Int. (2012): 29:920–7.

11. Culnan E, Kloss JD, Grandner M. A prospective study of weight gain associated with chronotype among college freshmen. Chronobiol Int. (2013): 30:682–90.

12. De Castro JM. The time of day of food intake influences overall intake in humans. J Nutr. (2004): 134:104–11.

13. Van der Heijden AA, Hu FB, Rimm EB, van Dam RM. A prospective study of breakfast consumption and weight gain among U.S. men. Obesity. (2007): 15:2463–9.

14. Morse SA, Ciechanowski PS, Katon WJ, Hirsch IB. Isn’t this just bedtime snacking? The potential adverse effects of night-eating symptoms on treatment adherence outcomes in patients with diabetes. Diabetes Care. (2006): 29:1800–04.

15. Keim NL, Van Loan MD, Horn WF, Barbieri TF, Mayclin PL. Weight loss is greater with consumption of large morning meals and fat-free mass is preserved with large evening meals in women on a controlled weight reduction regimen. J Nutr. (1997): 127:75–82.

16. Garaulet M, Gómez-Abellán P, Alburquerque-Béjar JJ, Lee YC, Ordovás JM, Scheer FA. Timing of food intake predicts weight loss effectiveness. Int J Obes. (2013): 37:604–11.

17. LeCheminant JD, Christenson E, Bailey BW, Tucker LA. Restricting night-time eating reduces daily energy intake in healthy young men: a short-term cross-over study. Br J Nutr. (2013): 23:1–6.

18. Nedeltcheva AV, Kilkus JM, Imperial J, Schoeller DA, Penev PD. Insufficient sleep undermines dietary efforts to reduce adiposity. Ann Intern Med. (2010): 153:435–41.

As escalating health care costs continue to significantly impact on corporate profits, many companies are realizing that proactive measures must be taken to manage these costs.

According to CIRCADIAN studies on financial costs associated with 24/7 operations, U.S. businesses spend an additional $36.5 billion annually on health care to support 24/7 operations.1

In most cases, the distinct health risks faced by shiftworkers can be controlled, monitored and potentially reduced through a collaborative effort of both management and workers.

Knowing these crucial factors will facilitate the design of programs that improve employee health and enhance productivity while also reducing the costs, risks and liabilities of shiftwork operations.

1. Gender

Gender has been recognized as a factor affecting shiftwork tolerance, as several studies have found that men have a greater tolerance for shiftwork than women.2

Several studies have reported that female shiftworkers tend to have more sleep-related problems than male shift workers.4,5,6,7

In particular, one study found that female shiftworkers report difficulties falling asleep, problems with insomnia and using sleeping aids to fall asleep more frequently than male shift workers.2, 4

Sleep & Gender

Because female shiftworkers report needing more sleep than men, a large disparity exists between women and men in terms of perceived sleep needs and obtained sleep.

Not surprisingly, the major problem is related to the night shift. While male and female shiftworkers report getting similar amounts of sleep when working the morning and evening shifts, 48% of female workers get six hours of sleep or less when working the night shift, compared to 41% of men (Figure 1).3

Figure 1: Sleep duration for men and women across different shifts3

Shift Type and Hours of Sleep  

Gender differences in sleep quality also occur on the night shift. Twenty-eight percent (28%) of female shiftworkers report “poor” sleep when working the night shift, compared to just 20% of male shift workers.3

Fatigue at Work

Female shiftworkers report feeling tired while working more frequently than their male counterparts.3

However, male shiftworkers report nodding off and making mistakes while working more often than women.3

2. Age

Problems with work performance tend to increase with age, the critical age being 40-50 years, when based on measures of subjective sleepiness, performance tests, recovery after work and sleep time.2

However, in terms of the risk of developing shiftwork related health problems and shiftwork tolerance, research studies report more favorable outcomes for older workers.3

This may be due to the “healthy shift worker effect”, in which older workers represent the individuals who are healthier and have always been better at coping with shift work, even at a younger age. Previous experience with shiftwork clearly influences one’s tolerance to shift work.

Overall, adjustment to shift schedules seems to improve with age and shiftwork experience. The percentage of shiftworkers reporting that their health would improve with a different schedule decreases from 51% for the group 25-34 years old, to 27% for workers aged 55 or older.3

3. Circadian Profile

A person’s “circadian profile” tends to affect shiftwork adaptation. Three main characteristics have been extensively evaluated: morningness/eveningness, flexibility of sleeping habits, and one’s ability to overcome drowsiness.

Morningness/Eveningness

Morning types, or “larks,” are naturally more alert in the morning than in the evening, and their circadian rhythms (temperature, alertness, etc.) reach a maximum earlier in the day. The opposite is true for evening types, or “owls.”

Scientists have demonstrated that morningness/eveningness is linked to a specific set of genes.

Morningness is also associated with an increased rigidity in sleep patterns—morning types find it more difficult to sleep during the morning than evening types, which further decreases morning types’ adaptation to night work.3

Shiftworkers in 24/7 operations who prefer to get up late (after 9 a.m.)—evening types—report sleeping more hours and getting better sleep on the night shift.3

Surprisingly, evening types report more problems adapting to their work schedule.3

Flexibility of Sleep Habits

Flexibility of sleep habits indicates an individual’s self-perceived ability to sleep at different times during the day or night. The ability to overcome drowsiness defines their ability to sustain alertness.

Ability to Overcome Drowsiness

Researchers have found that the ability to overcome drowsiness is the best indicator of shiftwork tolerance after three years of shiftwork.3

Both flexibility of sleep habits and ability to overcome drowsiness have been found to be related to a better long term shiftwork tolerance.3

4. Psychological and Behavioral Factors

Personality

Two psychological factors, extroversion/introversion and neuroticism, have been widely studied in relation to shiftwork tolerance. Several studies have found that extroverts adjust somewhat faster than introverts to shift work.2

However, neither extroversion nor neuroticism have any value in predicting adaptation to shift work.2

Locus of Control

Locus of control (that is, the internal versus external attribution of control with regard to managing problems) has recently been introduced as a factor affecting shiftwork tolerance – especially in regards to one’s locus of control in terms of shift work.

Internal locus of control (when the individual feels that rewarding experiences are contingent upon their own behavior and attributes) has been associated with better shiftworktolerance.3

Commitment to Shiftwork

Individual strategies for coping with shiftwork have been evaluated and seem to be a promising factor in predicting shiftwork tolerance.

Commitment to shiftwork means that workers are willing to schedule their lives around working non-traditional hours. Correct sleeping habits, appropriate exposure to bright light, good nutritional practices, and physical exercise may all have a crucial effect on shiftwork tolerance.

In fact, “commitment to shift work” has been cited by several authors as the most important individual factor affecting shiftworktolerance.3

5. Social Factors

Family and social factors can also affect one’s adaptation to shift work. It’s evident that the support spousal or partner support plays a pivotal role in the one’s adaptation to shift work.

Not surprisingly, the presence of children increases domestic responsibilities and may result in more difficulties adapting to a shiftwork lifestyle.

Shiftworkers with good family lives report better health status.3 This finding could be related to an absence of family conflict—a recognized source of stress—for these workers.

Long commutes interfere with everyday life, restricting free time and reducing sleep. Workers with commutes that are 45 minutes or longer have been found to report higher stress levels, more health problems, and higher absenteeism rates than workers with commutes of 20 minutes or less.3

Shiftwork Lifestyle Training

Most shiftworkers don’t know how to adjust their lifestyle to minimize the negative effects of working around the clock. As a result, workers’ job performance, safety, health, and family life suffers as company profits and productivity fall.

Training workers on how to manage a shiftwork lifestyle is a powerful tool for improving your employees’ physical and psychological well-being, thereby increasing morale and effectiveness.

In fact, research reports have found that turnover and absenteeism rates are higher in facilities that do not provide some type of shiftwork lifestyle training.

Download Our Free White Paper

Download our complementary CIRCADIAN® white paper, “Shiftwork Lifestyle Training: Employee and Employer Benefits”

Managing a Shiftwork Lifestyle Training alt
About CIRCADIAN®

CIRCADIAN® is the global leader in providing 24/7 workforce performance and safety solutions for businesses that operate around the clock.  Through a unique combination of consulting expertise, research and technology, software tools and informative publications, CIRCADIAN helps organizations in the 24-hour economy optimize employee performance and reduce the inherent risks and costs of their extended hours operations.

REFERENCES

1.CIRCADIAN. (2003). Financial Opportunities in Extended Hours Operations: Managing Costs, Risks, and Liabilities. Costs based on 2014 inflation rates.

2.Saksvik, I. B., Bjorvatn, B., Hetland, H., Sandal, G. M., & Pallesen, S. (2011). Individual differences in tolerance to shift work–a systematic review. Sleep medicine reviews, 15(4), 221-235.

3.CIRCADIAN. (2003). Health in Extended Hours Operations: Understanding the Challenges, Implementing the Solutions.

4.Marquie, J. C., & Foret, J. (1999). Sleep, age, and shiftwork experience. Journal of sleep research, 8(4), 297-304.

5.Rotenberg, L., Portela, L. F., Marcondes, W. B., Moreno, C., & Nascimento, C. P. (2000). Gender and diurnal sleep in night workers at a Brazilian industry. Shiftwork in the 21 st Century. Challenges for Research and Practice, 305-309.

6.Admi, H., Tzischinsky, O., Epstein, R., Herer, P., & Lavie, P. (2007). Shift work in nursing: is it really a risk factor for nurses' health and patients' safety?. Nursing economic$, 26(4), 250-257.

7.Rouch, I., Wild, P., Ansiau, D., & Marquié, J. C. (2005). Shiftwork experience, age and cognitive performance. Ergonomics, 48(10), 1282-1293.


The process of changing schedules can be daunting, especially for the workers; however, there are a number of processes that can be implement to ease the transitioned.

Based on interviews with shift work experts and 24-hour managers, CIRCADIAN suggests these 9 tips to help your workers manage a shift schedule transition.

1. Don’t over rely on overtime

Excessive overtime can be the downfall of an otherwise successful scheduling change. Avoid extending scheduled shifts and ensure that workers experience the primary benefit of 12s — increased days off.

To avoid overtime-related fatigue problems, here are a few guidelines to follow:

  • Prohibit overtime on scheduled work days, except in emergencies.
  • Even in emergencies, limit shifts to 14 hours unless the worker has the next day off — especially with shifts that include overnight hours.
  • Don’t call in workers on their days off more than two or three times per month.
  • Monitor overtime by individual so you can identify workers who are accruing excessive overtime.

Following these guidelines can help your company avoid being at risk for fatigue-related accidents and potentially reduce employee burnout and turnover rates.

2. Permit multiple short breaks

To maintain fairness for workers, along with avoiding fatigue and vigilance problems, the work-to-break ratio should remain the same after a schedule change.

Allowing additional short breaks – even as many as 4-5 breaks per shift – can be helpful in the transition from 8- to 12-hour shifts. Frequent, 10-15 minute breaks allow workers time for revitalizing activities (a short walk, a snack or a call home) that reduce feelings of monotony.

3. Cross train

Effective cross training can increase job satisfaction (reducing turnover in the long run) and make the physical and mental challenges of 12 hour shifts more manageable.

In physically demanding jobs, workers who use the same muscles for the entire shift are at risk for repetitive stress injuries. In less intense job positions, monotony can set the stage for boredom and an increase in fatigue-related incidents.

To avoid these risks, workers should be trained to responsibly to handle numerous tasks.

4. Focus on communication

There is a potential for communication breakdowns to occur when scheduling 12-hour shifts. Breakdowns in communication most frequently occur with schedules that provide workers with 6- or 7-day breaks within a given shift cycle.

To avoid this issue, consider developing a short debriefing process for workers that lights any changes that occurred while they were gone.

Have workers come to work 15 minutes following several days off. Another solution is to establish a message board for important updates or to use a computer messaging system.

5. Require managers to work 12s

Managers should regularly experience working a 12 hour shift schedule; however, it’s impractical to expect all managers to work the same 12-hour schedule as employees.

Requiring managers to work at least some 12s opens the lines of communication between management and workers; it also improves worker morale by demonstrating that management takes a genuine concern in the realities of their jobs.

One reasonable approach is to require daytime managers to work two 12-hour shifts per month, possibly in exchange for one 8-hour day off.

6. Establish an internal review team

An internal review team can service as an everyday liaison to other workers and meet formally every three months to identify trends.

To identify areas for improvement, create a team comprised of workers, with at least one representative from each job function. The team can pass on any insights to a senior-level management.

While there may be general satisfaction with a 12-hour schedule, there is always room for improvement.

7. Hold team-building social functions

Team building social functions boost team spirit among crews, and 12s make it easier to for workers to get together outside of work.

On any given day, half of your shift workers have the whole day off (whereas with 8s, three-quarters of your workforce is either on the job or working later that day).

Capitalize on this benefit by holding occasional morale-boosting events, such as dinners or softball games.

8. Encourage exercise

Workers who exercise frequently have improved morale, alertness, mood, health and sleep at home (provided the exercise isn’t too close to bedtime). Allowing for the opportunity to exercise at work is often incredibly well-received by workers.

Some companies allow people to exercise while they work, putting treadmills, rowing machines or stationary bikes in control rooms. If this isn’t feasible at your facility, consider furnishing a break room with exercise equipment, light weights, and a TV with aerobics DVDs, etc.

9. Seek out shiftwork-friendly products

Make 12-hour shifts easier for workers by installing shiftwork-friendly products designed to minimize fatigue and stress, such as: ergonomically-correct chairs, high-top stools for standing workers, computer screens that relieve eyestrain, and “anti-fatigue” floor mats.

Choose durable products, as they are used 24 hours a day. With office furniture, find products that reduce discomfort and backaches, yet aren’t so comfortable that they set the stage for falling asleep.

Want to learn more about 12-hour shifts?

Download our free white paper "Advantages & Disadvantages of 12-Hour Schedules: A Balanced Perspective"

12 hour shift schedules white paper download white paper About CIRCADIAN

CIRCADIAN® is the global leader in providing 24/7 workforce performance and safety solutions for businesses that operate around the clock.  Through a unique combination of consulting expertise, research and technology, software tools and informative publications, CIRCADIAN helps organizations with traditional and/or extended operating hours optimize employee performance and reduce the inherent risks and costs of sleep deprivation and fatigue.

 

energy drinksWith sleep constantly challenged by the demanding nature of our daily lives. Many of us resort to energy drinks and other caffeinated beverages to power through the day. But do you ever wondering how your body is affected by these drinks? Are they healthy? Moreover, are they safe?

Below are five crucial facts that you need to know before consuming your next energy drink. Knowing these facts could benefit your health and potentially save your life.

1. Energy drinks require no FDA preapproval when choosing ingredients

Traditional sodas are considered to be beverages, and therefore are subject to strict FDA regulations on caffeine contents and ingredients. On the other hand, energy drinks are classified as dietary supplements, and have avoided many FDA regulations due to a loophole created by the Jolt Cola beverage company. Because of this, energy drink ingredients must be listed, however there’s no requirement to list the specific amount of each ingredient existing in these “drinks”.1

2. Per ounce, energy drinks can contain over 5x more caffeine than regular coffee

Energy shots, like 5-Hour Energy, contain 100 mg of caffeine per ounce as compared to regular coffee, which contains approximately 18 mg of caffeine per ounce.2 What does this mean for the typical energy drink consumer?

Well, unlike hot coffee, which is often sipped slowly, energy drinks tend to be “gulped,” and are finished quickly. Therefore, the peak caffeine level of an energy drink will be reached quickly. With a long half-life, energy drink users can quickly find themselves in danger of reaching very high levels of caffeine in the body, especially after consuming several drinks in a short amount of time.

3. The half-life of caffeine in energy drinks can last up to 10 hours

The human body absorbs 99% of caffeine, reaching peak levels within 30-75 minutes.3,6 How long does this caffeine rush last? Well the half-life of caffeine can vary dramatically, with its effects lasting anywhere from 2.5–10 hours.4 There are several factors that can influence the half-life of caffeine, such as: 3-7

    • Impaired liver function
    • High levels of caffeine consumption (increases half-life)
    • Cigarette smoking (decreases half-life)
    • Weight
    • Age
    • Medications (i.e. oral contraceptives, antibiotics, theophylline, Echinacea)
    • Health Status
    • Gender
    • Individual differences

4. A variety of physiological side effects are associated with heavy caffeine use

There are no hard and fast rules on how much caffeine is safe, as caffeine sensitivity can vary widely depending on the individual; however, several major medical organizations have published guidelines for caffeine intake. For example, the Mayo Clinic recommends that people consume no more than 200-300mg of caffeine per day, which equates to roughly one 5-Hour Energy Shot.

In fact, one study found that people given a 300 mg shot of caffeine experienced the following symptoms (in order of prevalence):

    • Restlessness or muscle tremor
    • Heart palpitations
    • Dizziness
    • Headache
    • Diarrhea
    • Wakefulness
    • Polyuria (excessive urination)
    • Increased sweating
    • Abdominal pain
    • Ear/eye problems
    • Vomiting or nausea
    • Delirium

5. Energy drinks have been linked to death and cardiac failure

Between 2004 and 2012, 5-Hour Energy amassed 92 incident reports with 13 fatalities, Monster had 40 reports with 5 fatalities, and Rockstar had 13 reports with no fatalities. Over 50 of the incidents for all three energy drinks list heart problems (chest pain, arrhythmia, cardiac arrest, etc.) in the events, according to the U.S. Food and Drug Administration.

In 2012, Monster Energy received a great deal of attention, when the FDA published a report listing

Monster Energy drinks as a possible contributing factor to the deaths of five people over three years. One of those people was a 14-year-old Maryland girl, whose death certificate stated that she died of “cardiac arrhythmicity due to caffeine toxicity” after drinking two 24-ounce cans of Monster in 24 hours, which exacerbated a pre-existing heart condition. The family of the girl is now suing Monster Energy for failing to provide adequate warnings about the risks of consuming their drinks.

It can’t be all bad, right?

While the majority of studies published on energy drinks focus on the negative effects, not everyone agrees with their assessments. For example, energy drinks do appear to enhance physical performance. Drinking energy drinks also improves driving performance in sleepy subjects – including reducing driving mistakes, swerving, and self-reported sleepiness and alertness.9

So is it safe to have an energy drink?

Bottom line: Yes, but use energy drinks in moderation. If you can’t get going in the morning or are dragging during the middle of your night shift, an energy drink now and then is fine. But remember, whether you get your caffeine from energy drinks, soda, or coffee, read the labels (or do some research) and be aware of the levels of caffeine and other ingredients you’re putting in your body. As long as you use caution and keep track of what you’re consuming, feel free to enjoy the benefits of energy drinks – without ignoring the risks.

Want to learn more about energy drinks? Visit CIRCADIAN to download a free white paper titled

Energy Drinks: The Good, the Bad, and the Jittery that provides further information about energy drinks.

 

REFERENCES
1. Energy “Drinks” and Supplements: Investigations of Adverse Event Reports. U.S. Food and Drug Administration. http://www.fda.gov/Food/RecallsOutbreaksEmergencies/SafetyAlertsAdvisories/ucm328536.htm. Accessed June 20, 2014.
2. Caffeine in coffee: US Food and Drug Administration
3. Carrillo JA and Benitez, J (2000) Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clinical pharmacokinetics, 39: 127-153.
4.Kaplan GB, Greenblatt DJ, Ehrenberg BL, Goddard JE, Cotreau MM, Harmatz, JS and Shader RI (1997) Dose-dependent pharmacokinetics and psychomotor effects of caffeine in humans. Journal of Clinical Pharmacology, 37:693-703.
5.Caffeine. How much is too much? Mayo Clinic. http://www.mayoclinic.org/healthy-living/nutrition-and-healthy-eating/in-depth/caffeine/art-20045678. Accessed on June 20, 2014.
6.Mandel, HG (2002) Update on caffeine consumption, disposition and action. Food and Chemical Toxicology, 40:123
7.Magkos F, and Kavouras S (2005) Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action. Crit Rev Food Sci Nutri 2005, 45: 535-562.
8.Carrillo JA and Benitez J (1996) CYPlA2 activity, gender and smoking, as variables influencing the toxicity of caffeine. British Journal of Clinical Pharmacology, 4(1): 605-608.
9.Reyner LA, and Horne JA (2002) Efficacy of a ‘functional energy drink’ in counteracting driver sleepiness. Physiological Behavior, 75(3): 331–335.

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