Dr Dingle's Blog / immune system
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Sleep, like most other processes in our body, is mediated by the interaction of cytokines and chemokines with neurotransmitters (Dilger & Johnson, 2008). During infection our sleep patterns change and interactions of cytokines, especially IL‑1 and IL‑1 2 and the neurotransmitter serotonin amplify (Dantzer et al. 2008; Lange et at. 2006). During sleep, it has been suggested that, the synapses not used during the day's activities are given an opportunity to prime and regenerate, cognitive function also rejuvenates, memories are consolidated and on a cellular level glycogen stores can re‑fuel. However, sleep deprivation has been associated with inflammatory based diseases including obesity, Cardiovascular Disease and Diabetes (lmeri & Opp, 2009).
Sleep deprivation has been shown to further enhance end stage renal disease, decrease vaccine efficacy as attested with both Influenza and Hepatits A vaccines, prolong wound healing, lengthen critical care stays and enhance depression or other psychiatric disorders (Lange et al. 2003; Miller et al. 2004; Koch et al. 2009).
Several recent studies report that reducing sleep to 6.5 or fewer hours for successive nights causes potentially harmful metabolic, hormonal and immune changes. All of the changes are similar to those detected in the normal aging process (Cobb, 2002) and so sleep deprivation could be the biggest indicator of how long you live (Sateia, et al., 2004). There is a strong link between sleep deprivation and low immune system function (Redwine, et al., 2003). A reduction of sleep makes people more prone to infection and potentially more prone to cancer; one study found that poor sleep was associated with a 60 percent increase in breast cancer.
In one study of 153 volunteers who spent less time in bed, or who spent their time in bed tossing and turning instead of snoozing, were much more likely to catch a cold when viruses were dripped into their noses, while those who slept longer and more soundly resisted infection better. The study showed that even relatively minor sleep disturbances can influence the body's reaction to cold viruses ( Cohen et al Archives of Internal Medicine). The men and women who reported fewer than seven hours of sleep on average were 2.94 times more likely to develop sneezing, sore throat and other cold symptoms than those who reported getting eight or more hours of sleep each night. Volunteers who spent less than 92 percent of their time in bed asleep were 5 1/2 times more likely to become ill than better sleepers, they found.
The benefits of sleep include:
Being physically and mentally alert;
Having more energy;
Making fewer mistakes (including causing accidents);
Feeling psychologically and emotionally recovered;
and to experience:
Improved cognitive function;
Higher stress tolerance and resilience;
Normal body balance;
Reduced risk of CVD, diabetes and cancer;
Living longer; and
during sleep the mind is cataloguing our memories and deciding what to keep and what to throw away it is making memories stronger. It also seems to be reorganizing and restructuring memories.
It’s not possible to learn something new when you sleep, like a foreign language, but you can reinforce something you already know.One study found that students learned to play a series of musical notes better after listening to them during a 90-minute nap. The research shows that memory is strengthened for something you’ve already learned. Rather than learning something new in your sleep.
A review of studies on sleep found that we tend to hold on to the most emotional parts of our memories.
Getting enough sleep is associated with energy, joy, optimistic thinking and coping with negative emotions.
Stages of Sleep
4 to 8
Transition between sleep and wakefulness
Eyes begin to roll and close
Consists of mostly theta waves with some brief periods of alpha waves (similar to waves of wakefulness)
Stage lasts 5-10 mins
8 to 15
Brain wave peaks become higher
Spontaneous periods of muscle tone mixed with periods of muscle relaxation
Heart rate and temperature decrease
Stage last 5-10 mins
2 to 4
Deep Sleep or Delta sleep
Very slow brain waves
0.5 to 2
The last of deep sleep before REM begins.
Consist mostly of Delta waves
Beta waves have a high frequency and occur when the brain is active when asleep and awake.
Frequent bursts of rapid eye movement (REM) and muscle twitches.
Increase in heart and breathing rate
Vivid dreaming occurs here.
When a person falls asleep and wakes up is largely determined by their circadian rhythm, a day-night cycle of about 24 hours. Circadian rhythms greatly influence the timing, amount and quality of sleep (Lockley et al. 1997).
Literally hundreds of circadian rhythms have been identified in mammals (Campbell 1993). Among the numerous systems and functions mediated by the circadian timing system are, hormonal output, core body temperature and metabolism. The circadian clock is believed to sit in the suprachiasmatic nucleus (SCN) located in the hypothalamus of the brain. It was thought that processes now linked with circadian timing e.g. sleep wake cycles, were due solely to environmental cues, for example solar activity, it is now recognised however that these biological rhythms are regulated by factors inherent to the organism (Campbell 1993). A circadian rhythm displays a 24 hour cycle of wakefulness and sleep synchronised with the world’s night/day clock (Mansuy et al, 2003). Everyone’s cycle will vary depending on behavioural and psychological factors (Mansuy et al, 2003). The most typical pattern will be low alertness in the mornings as we wake, to highly alert mid afternoon (Swain et al, 2007).
The natural circadian rhythm in the body, which maintains a regular sleep-wake cycle, makes important contributions to physiological processes and psychological health. The normal rhythm is reset daily by the influence of bright light in the morning. Shift-workers, who may work at night and sleep in the daytime, and blind people may have difficulty maintaining a normal sleep-wake cycle because the natural environmental cues are miss-timed (Morris 1999). Studies show that shift work is one the greatest influencing factor causing an alteration in an individual’s cycle along with sleeping disorders (Baulk, 2008). Altering the circadian cycle can lead to periods of decreased alertness leaving people extremely vulnerable to accidents and injuries (Andersen et al, 2009).
Our sleep patterns appear to be polyphasic. In one experiment, subjects were exposed to 14 hours of darkness; then they remained in a state of quiet rest for about two hours before falling asleep. They then slept for four hours, awakened from a dream, spent another two-hour period in quiet rest, and then fell asleep again for four hours more. The subjects awoke at 6 a.m. each morning from their dream sleep and then spent two hours in quiet rest before arising at 8 a.m. These subjects followed their own natural rhythms, sleeping for eight hours with blocks of time at quiet rest (Wehr, S.E, 1996). This polyphasic sleep appears to be a pattern in many mammals. We experience hypnagogic imagery – a state described as dreaming, drowsy, floating, wandering – every night just before we fall asleep. Every night before we go to sleep we spend a few minutes in a state of relaxed wakefulness characterised by drifting thoughts and alpha brainwaves.
Another interesting method for lessening the impact of sleep deprivation was through a study that found there were certain hours better to sleep through the night. A new Stanford University study on the science of sleep deprivation suggests that early morning sleep is more restful than a middle‑of‑the‑night nap. In a study of two groups of men they found that early‑morning sleepers scored higher on wakefulness tests and on measures of sleep efficiency. (Stratton, 2003) Although this study shows that there may some advantages to when you get your sleep it is more an avoidance of the problem rather than a solution.
We are also influenced not just by sleep but also our perceptions of its quality. If we think we’ve had a wonderful sleep last night, we feel and perform better, even if our sleep was actually the same as usual. In this study researchers randomly told some people they’d had better sleep than others after they were hooked up to some placebo brain sensors). When they were given a cognitive test the next day, those who’d been told they slept the best also did the best in the test.
Part 3 and more coming
In the new year, with all the mention of healthy foods it is also important to put the role of physical activity in perspective and perhaps make that one of our top goals for 2017. Up until 10,000 years ago, humans were still living a nomadic, hunter-gatherer lifestyle, scouting the landscape in the search for food, which placed a high level of physical stress on the body. Even going back just 200 years, humans were much more physically active than they are today, living a predominantly agrarian life, running farms and crop fields.
The genetic and physical make up of humans has not changed significantly since those days, but our levels of physical activity have. In addition, with each subsequent generation, levels of physical activity have reduced - the highest participation in physical activity occurs amongst school-aged children and adolescents, but this tends to decrease with age. A study of 1032 participants, found that after age 9, physical activity decreased by 38 minutes per year, while weekend physical activity decreased by 41 minutes per year. Additionally, at around 13.1 years in girls and 14.7 years of age in boys, the level of physical activity went below the recommended 60 minutes of physical activity per day 1.
In Australia, conservatively more than 8000 deaths occur annually due to lack of physical activity, costing not only lives and suffering, but also millions of dollars to the health care system. Increased physical activity has been associated with increased life expectancy, as well as reduced risk of heart disease, stroke, hypertension, obesity, diabetes, cognitive decline and Alzheimer’s disease 2,3 and much more. The single biggest killer in Australia today is cardiovascular disease (CVD) and an individual who undertakes regular physical activity, is half as likely as his sedentary counterpart to contract cardiovascular disease (CVD) 4,5,6.
A large number of studies have reported that physical activity not only reduces the risk of, but also protects against coronary heart disease 7,8,9. Additionally, in a cohort study of 743,498 men, aerobic fitness in late adolescence was a good predictor of a heart attack later in life. However, obese men with high aerobic fitness had a higher risk of heart attack than lean men with low aerobic fitness. Therefore, it is important to be physically active and maintain a healthy weight to keep the risk of heart attack at it's lowest 10.
High Blood pressure, or hypertension, is characterised as any blood pressure over 140/90, with the optimal being 120/80. Exercise resulting in weight loss, has been shown to have significant benefits in reducing blood pressure. Numerous large population-based studies 11,12,13 have demonstrated an inverse relationship between physical activity and blood pressure. In addition, interventional studies where individuals were trained to do more physical activity, demonstrated that increased exercise works to lower blood pressure 14,15. Furthermore, a randomized, controlled trial, found exercise training is effective in lowering blood pressure in overweight, sedentary patients with high-normal or mildly elevated blood pressure, and that weight loss is of added benefit when combined with aerobic training 16.
Physical activity has been shown to decrease mortality and increase life expectancy. In a study of 252,925 men and women, those doing moderate activity (at least 30 minutes on most days of the week) decreased mortality risk by 27%, whereas those who met recommendations for vigorous activity, at least 20 minutes, three times per week- not much if you really think about it, had a 32% reduction of mortality risk 17 a finding consistent with many other studies 18,19,20. And it is not too late to start now no matte how old you are. In a 4.9 year longitudinal study of 9,777 men, it was discovered that those who improved from unfit to fit, reduced their all-cause mortality risk by 44% and cardiovascular mortality by 52%, compared to those who remained unfit 21.
Inflammation and Triglycerides
Inflammation is the underlying condition in many chronic illnesses, including CVD and cancer. Physical activity decreases inflammation and additionally, those with higher cardio fitness levels, have lower circulating levels of inflammation markers such as of IL-6, CRP and fibrinogen 22. Physical activity and fitness are also associated with improved plasma lipid (fat) profiles, including the ratio of high-density lipoproteins (HDLs) to low-density lipoproteins (LDLs), and plasma triglycerides. Triglycerides decrease by 24%, while HDLs increase by about eight percent, in response to regular physical activity 23,24. Studies have also shown similarly favourable findings in diabetes 25.
Low levels of physical activity and cardio-respiratory fitness, are associated with the development of metabolic syndrome and type 2 diabetes. In one study, older men and women, who were in the lowest third of cardio-respiratory fitness, had a 10-fold higher risk of developing metabolic syndrome than those who were in the highest third. There was a strong inverse association between fitness and metabolic syndrome, as well as a significant relationship to all the components of metabolic syndrome 26.
Additionally, a low fitness level has been found to be an important risk factor for incidence of type 2 diabetes - men with the lowest 25% of fitness had a relative risk of diabetes that was four times higher compared to those in the highest 25% 27. It seems that both physical activity and fitness are separately and independently associated with metabolic risk profile 28 i.e., they are both contributing factors to reducing the risk of metabolic syndrome.
Incorporating more exercise to the day-to-day routine, is crucial for sufferers of type 2 diabetes. In type 2 diabetes, insulin is in short supply, or is difficult for the body to utilize – exercise, has been shown to improve the body's sensitivity to insulin. Not only does exercise help improve the diabetic condition, it can also help reduce the risk of developing type 2 diabetes altogether. A Harvard University study examining the exercise habits of more than 70,000 women, showed that a 40 minute walk every day reduced type 2 diabetes risk by 40%, and with a longer walk the risk could be decreased by an even larger percentage.
Exercise also helps to increase blood flow, which is important to help reduce the risk of neuropathy, a common neurological disorder associated with type 2 diabetes. In addition, studies have shown that a short-term reduction in daily physical activity, negatively affects insulin sensitivity.
One small step for diabetes. Just as important as the amount of exercise for diabetes is the timing. Much of the damage done in diabetes is done by the circulating sugar and or high insulin levels causing oxidation, inflammation and acidosis. Going for a walk 10 or so minutes after eating, particularly after a large dinner can have a direct and rapid impact on lowering blood sugar and subsequently the amount of insulin required to control the sugar. It is very important to bear in mind that this small change to a days routine can make a big difference in managing diabetes.
The immune system may be enhanced or depleted, depending on the intensity of physical activity 29 - both too little and too much exercise is proven to be detrimental to the immune system. For example, there is a high incidence of upper respiratory tract infections (URTI) in professional athletes (50-70% getting an infection in the 2 weeks following a marathon), which suggest that too much exercise can act as an immunosuppressant. Similarly, longitudinal studies have shown that moderate exercisers can overcome URTIs in half the time that an elite athlete does. Studies have also demonstrated similar findings with a decrease in mucosal (salivary etc) immunity with excessive exercise 30. Whilst excessive exercise may have a detrimental effect to the immune system, research has suggested that moderate levels of exercise can be beneficial to the immune system. Blood lymphocyte concentrations of a sedentary person are comparable to that of a high performance athlete, whereas the lymphocyte count is higher in a person who undertakes regular moderate exercise. Research suggests that regular, but not excessive exercise, improves the immune system 31,32.
Osteoarthritis (OA) is the second most common cause of disability in the developed countries and Rheumatoid Arthritis (RA), has also become a major health concern 33,34. Both are degenerative diseases of the joints, which can be improved with the implementation of moderate aerobic and weight bearing exercise. Research shows that short term gains of muscle strength, and a range of movement can increase the functionality of patients suffering from OA or RA. In addition, improved fitness levels have been shown reduce the risk of gout, another form of arthritis, in physically active men 35.
Different forms of activity have shown to have important impacts on our hormones and endocrine system. In the period prior to, during and after exercise, the endocrine system reacts in order for the body to function effectively and at optimum levels. Simultaneously, hormones governing the body's regulation, such as epinephrine and norepinephrine, are produced in greater quantities to assist the body in operating efficiently.
Additionally, physical activity has demonstrated positive effects on mental health, and has been shown to be more effective than drug therapy without any deadly side effects and works well alongside counselling therapy for depression and anxiety. It has been shown to improve individuals’ mood, reduce anxiety and stress, and increase self-esteem. Physical activity has been demonstrated to bring about positive structural brain changes and plasticity, as well as alter the production of neurotransmitters including Gamma-Aminobutyric acid (GABA). If you want to be smarter make sure you get enough exercise.
On the other side of the equation a number of medications can have a negative impact on the level of physical activity. For example, the most prescribed drug worldwide, statins, which are used to lower cholesterol, reduce the effectiveness of exercise. A recent study found the statin previously sold under the brand name "Zocor," hindered the positive effects of exercise for obese and overweight adults by 85%. The study also found that this statin, decreased the effectiveness of the mitochondria (power house) in the muscles.
It seems that statins block the ability of exercise to improve the fitness levels of the individual that takes them. Participants in the exercise-only group increased their cardio-respiratory fitness by an average of 10% compared to a 1.5% increase among participants also prescribed statins. Additionally, skeletal muscle mitochondrial content, the site where muscle cells turn oxygen into energy, decreased by 4.5 percent in the group taking statins while the exercise-only group had a 13 percent increase, a normal response following exercise training.
With the new year upon us it is time to get serious about our physical activity. There are just far too many benefits. It doesn’t have to be much just a little bit every day is enough to get you started on a better health journey.
- Nader, et al., 2008
- Lindsay et al., 2002
- Kohl 2001; Kujala 2004
- Berlin and Colditz 1990
- Miller, Balady and Fletcher 1997
- Rastogil et al., 2004
- Sundquist, Malmstrom and Johansson 1999
- Fletcher et al., 1996
- Kiess et al., 2001
- Hogstrom et al. 2014
- Criqui et al.,1982
- Hickey et al., 1975
- Miall and Oldham, 1958
- deVries, 1980;
- Jennings et al., 1986
- Blumenthal et al., 2000
- Leitzmann et al., 2007
- Manini et al., 2006
- Reis et al., 2009
- Heinzelmann and Bagley 2009
- Blaire et al., 1995
- Kullo et al., 2007
- Anderson and Anderson 1998
- Durstine et al., 2002
- Sigal et al., 2006
- Hassinen et al., 2008
- Sawada et al., 2003
- Steele et al., 2008
- Bruunsgaard and Pedersen 2000
- Pyne and Gleeson 2000
- Kendall, et al., 1990
- Rhind, et al., 1994
- Cote, 2001
- Kettunen and Kujala, 2004
- Williams, 2008