Circadian Rhythm

Timing Medication in Accordance With Body Clock Boosts Efficacy

All life under the sun possesses innate timing mechanisms that regulate crucial components for survival. In humans, a small part in the hypothalamus of the brain, the suprachiasmatic nucleus, oversees the individual clocks ticking away in every cell of the body. These biological rhythms dictate everything from cellular regeneration, hormone production and metabolic processes, to heart function, immunity and responses to stress. Right down to a molecular level, our biological lives are largely governed by these circadian rhythms.

Disruptions of circadian patterns are linked to a number of adverse physiological outcomes, such as an increased risk for heart disease, obesity and diabetes, as well as psychological conditions like anxiety, depression, schizophrenia and bipolar and borderline personality disorders. Recent research has also implicated circadian disruption in the onset and aggravation of neurological disorders such as dementia, Alzheimer’s disease and multiple sclerosis. The obvious influence of the body’s circadian clock makes a strong case for rethinking how we approach methods of treatment.

The Body’s Clock Determines Drug Response

Scientists have observed for some time that the modulation of human gene expression appears to be dependent on the body’s circadian clock, but the body clock’s relevance in therapeutic applications has only recently begun to be appreciated. Research in recent years has demonstrated that circadian rhythms indeed even bear influence on therapeutic treatment outcomes. For instance, studies have found that treatments for everything from allergies and blood pressure to cancer are markedly improved when timed to match the body’s internal clock.

Despite the mounting evidence for its importance, circadian activity is not often given consideration in a clinical setting. One of the main reasons for this is simply a lack of information on the molecular rhythms in humans. Hoping to help fill this data gap, scientists from Cincinnati Children’s Hospital Medical Center (CCHMC) have created a database analyzing genetic circadian rhythms.

The researcher’s efforts provide an invaluable look into numerous rhythmically expressed genes that are involved in the inner workings of drug transport and medication metabolism and further confirm that biological rhythms are key to the equation when considering treatments. The data their findings present should prove to be a useful resource for the budding field of chronopharmacology.

The team’s research efforts are detailed in Science Translational Medicine.

The Body Clock Regulates Half of the Protein-Coding Genome in Humans

Led by Dr. John Hogenesch, a biologist working in the Human Genetics and Immunobiology divisions at CCHMC, the group of scientists analyzed the data from thousands of tissue samples, which were comprised of 13 varied human tissue types that were collected from 632 donors. Utilizing a new method of analysis, the team constructed a database cataloging circadian patterns in human gene activity in hopes of gleaning insights into the genes regulating how drugs work.

According to the authors, the body clock regulates half of the protein-coding genome in humans. The team report in their article, “[N]early half of protein-coding genes were shown to be cycling in at least 1 of the 13 tissues analyzed. One thousand of these cycling genes encode proteins that either transport or metabolize drugs or are themselves drug targets.”

The researchers believe the discovery to have “clear implications” for circadian medicine. They state, “These results provide a useful resource for studying the role of circadian rhythms in medicine and support the idea that biological time might play a role in determining drug response.”

In a press release, Dr. Hogenesch commented, “we identified rhythms in gene expression across the body in a large and diverse group of people. It doesn’t matter if you’re male, female, young or old, or what your ethnicity is, your body’s internal clock regulates half your genome.” He further explained, “this includes drug metabolizing enzymes, transporters, and targets. Now we are learning which drugs hit clock-regulated products and may benefit from optimizing administration time in people.”

The team stresses that further research, including clinical trials, are needed before their findings can be applied in clinical practice.

An Algorithmic Approach: Cyclic Analysis

Possibly the largest barrier to seeing circadian timing applied in clinical settings is the lack of available data regarding the underlying clock mechanisms in humans. In hopes of helping to bridge the data gap, the team put into use a new algorithmic approach for studying the body’s timing mechanisms in relation to changes in gene activity.

The team used this new bioinformatics algorithm that they developed, referred to as CYCLOPS, which is short for “cyclic by periodic structure,” in order to analyze raw data of the genetic interactions from the donor tissues.

Out of thousands of genes that were found to cycle rhythmically in the different tissue samples, the authors report that it was “core clock genes” that were found to be the “most robust,” a finding which echoes previous studies into the genetic patterns of other vertebrates. Nearly a thousand genes were identified that code for proteins affecting how medications work.

A Strong Influence on Heart Medications

The first author of the study, Dr. Marc Ruben, commented, “overall this connects thousands of different drugs, both approved and experimental, to nearly 1,000 cycling genes. We found that genes that cycle in the human cardiovascular system are targeted by many of these drugs.”

Of those studied, the team reported observing the rhythmic cycling of 136 different medication targets in one of four heart tissue locations — the aorta, atrial chamber, as well as the coronary and tibial arteries. Many of the medication targets observed are considered “standard-of-care” marks for heart disease drugs, in particular, a family of medications referred to as “calcium channel blockers.” Calcium channel blockers are a class of drug that aid vascular relaxation in angina and hypertension patients by reducing the amount of calcium present in the cells of the heart and blood vessels.

The team’s efforts provide a good basis for future research into avenues of individualized treatment, but there are still challenges ahead. Dr. Ruben commented, “it’s not as simple as taking your medication in the morning. One in six US workers are now shift workers, so while it may be morning for most, it is bedtime for some. We need a robust way to measure body time to account for this.”

Meal Timing and Diet Alter Gut Health

May 11 by Ewcopywriting Leave a Comment

Every time we consume food, we’re also feeding the bacteria that call our bodies home. The human body plays host to trillions of microorganisms, including thousands of species of bacteria, fungi and viruses. These microorganisms actually outnumber our own cells, and the vast majority of them reside in our digestive system.

Referred to as the gut’s microbiota or gut flora, the microorganisms that live in the gastrointestinal tract play fundamental roles in immunity, nutrient absorption and vitamin production. The microbiota influences cardiovascular health, blood sugar and hormone regulation, brain development and even has the ability to affect our mood and behavior. Every individual has a microbiota that is completely unique to them, and any imbalance in these microbes can potentially lead to sickness, disease and mental decline.

Researchers have uncovered links between our gut flora and diseases and illnesses such as:

Alzheimer’s Disease
asthma
autism Spectrum Disorder
cancer
cardiovascular Disease
depression
diabetes
Multiple Sclerosis
obesity
Post Traumatic Stress Disorder

There are many factors that can contribute to the composition and continual balance of the gut microbiota. Among the most important and easiest factors to address are diet and meal timing.

How Diet Affects Gut Health

Different species of bacteria have been found to thrive on different types of foods, and even if you take a probiotic supplement, what you eat can vastly alter your gut flora. Where we live and the regional foods we consume even play a large part in our microbiota composition. For instance, a recent study published in the journal Frontiers in Nutrition found that a Mediterranean diet promoted a healthier gut than a Western diet.

In their study, the researchers demonstrated that a Mediterranean diet, which is typically higher in plant fibers, whole grains, fish and poultry than a Western diet, increased the amount of the beneficial bacteria Lactobacillus by up to seven percent. The Western diet, which tends to be lower in fiber, with higher amounts of fat and refined carbohydrates, only increased the number of beneficial bacteria by 0.5 percent.

Refined carbs and high-sugar foods are known to cause inflammation of the gut and promote the growth of bad bacteria. Research also indicates that the amount of and types of protein we consume alters the microbial diversity of our guts. For example, studies found that consumption of whey and pea protein increase the presence of certain beneficial gut bacteria while decreasing particular strains of pathogenic or bad bacteria.

How diet affects gut health is a large factor in our microbiota, but what we eat isn’t the only thing to consider when looking to improve your gut flora. Increasing research indicates that the size of meals and their frequency also impacts the gut’s microbial balance.

Meal Timing and the Effects on Your Gut

Most living organisms operate off innate circadian rhythms, and as it turns out, this includes our gut bacteria. A research article published in the scientific journal PLOS ONE demonstrated that bacteria commonly found in the human gut possess their own circadian rhythm and respond to fluctuations in the presence of hormones such as melatonin and tryptophan.

Our biological clocks are extremely sensitive to both the intake and restriction of energy. Research has shown that a disruption of these circadian rhythms can lead to numerous detrimental health effects such as diabetes, hypertension and irregular hormone levels. Structured eating regimens may provide the best way to avoid these disruptions and ensure optimal gut health.

Sometimes disrupting these internal clocks could prove beneficial, however. According to a recent study that was led by researchers from MIT and published in the journal Cell Stem Cell, it may be possible to shock our guts back to good health through fasting. In their study, the researchers discovered that a 24-hour fast in mice caused a metabolic switch that boosted the regeneration and reparation of gut stem cells.

In a study that was recently published by the American Diabetes Association, this reset of the gut microbiota that occurs with fasting was shown to have the added benefits of preventing blindness and promoting longevity. Yet another recent study, which was released by Experimental Biology, has shown that fasting may also improve heart function and help to slow the cardiac damage that accompanies heart failure.

The Bottom Line?

Our bodies are essentially more bacteria than they are human, and a proper balance to this bacteria is vital to our overall health, well-being, and longevity. The good news is that being more mindful of what we put into our bodies and when we do it are easy steps to correcting and maintaing the balance of this symbiotic relationship.

Meal Sizing Tips for Health and Weight Loss

Apr 10 by Ewcopywriting Leave a Comment

Breakfast is often regarded as the most important meal of the day. As famed nutritionist Adelle Davis said, “breakfast gets the day’s work done.” New research on meal size and weight loss gives credence to this conventional wisdom by showing that eating a larger, high-energy breakfast aids weight loss and blood glucose control when compared to having our largest meals at the end of the day or eating smaller, more frequent meals.

After conducting a previous study that highlighted the fact that front-loading the day’s calories affects weight loss and blood sugar levels in non-diabetic individuals, researchers from Tel Aviv University set out to determine whether the same effects would be seen in patients with Type 2 diabetes. Their findings, presented in March at the ENDO 2018 conference, echo previous research and confirm that meal size and schedule positively affect glucose balance and weight regulation in obese patients with Type 2 diabetes.

The Effects of Meal Size and Scheduling on Metabolism

We’re all aware of how important a healthy diet is to maintaining weight, but more and more, the research suggests that when we eat may be more important than what or how much we consume. Data released by the American Heart Association shows that eating patterns have greatly shifted away from the traditional three-a-day approach in a change that is ultimately detrimental to our health. Evolving lifestyles and erratic schedules have left most of us eating around the clock.

According to the lead study author, Daniela Jakubowicz, M.D., professor of medicine at Tel Aviv University, “the hour of the day, when you eat and how frequently you eat, is more important than what you eat and how many calories you eat.” This is because of how our body’s metabolism shifts and changes throughout the day. “A slice of bread consumed at breakfast leads to a lower glucose response and is less fattening than an identical slice of bread consumed in the evening,” Dr. Jakubowicz explained.

Because our internal clocks are so responsive to food supply or restriction, meal timing has serious implications on the development of obesity, Type 2 diabetes, and cardiovascular disease.

Meal Timing Affects Weight Loss Efforts

The team studied a group of 29 obese men and women with an average age of 69 who had Type 2 diabetes and received insulin treatments. The participants were randomly assigned to one of two different diets that consisted of an equal number of calories but scheduled meals at different intervals of the day. The first diet group (Bdiet) ate three meals a day that consisted of a large breakfast, a medium-sized lunch and a smaller dinner. The second diet group (6Mdiet) ate a traditional diabetic diet that consisted of six small meals and three snacks spaced evenly throughout the day.

After three months, patient data was analyzed. According to the data, the oft-touted advice to eat less, more often just may be false. Researchers found that overall, the Bdiet group lost an average of 11 pounds, while the 6Mdiet group actually gained around three pounds. Mean glucose levels dropped for the Bdiet group, but not the 6Mdiet group.

Meal Frequency Modulates Blood Glucose Levels

The Bdiet group needed considerably less insulin throughout the day, while the 6Mdiet group found they needed to increase their insulin usage. Reported feelings of hunger and cravings were decreased among the Bdiet participants but conversely increased in the 6Mdiet group.

The researchers noted a significant reduction in overall glycemia in as little as 14 days of following the Bdiet, suggesting that meal timing itself has a fast-acting beneficial effect on glucose balance. “This study shows that, in obese insulin-treated type 2 diabetes patients, a diet with three meals per day, consisting of a big breakfast, average lunch and small dinner, had many rapid and positive effects compared to the traditional diet with six small meals evenly distributed throughout the day: better weight loss, less hunger and better diabetes control while using less insulin,” Dr. Jakubowicz said.

When You Eat May Be the Key to Optimal Health

The team’s efforts are related to other findings on the critical effects of meal timing. An earlier study on prolonged delayed eating found that skipping breakfast or having the first meal of the day after noon caused weight gain, slowed metabolism, and produced an increase in cholesterol and insulin levels in participants. Both studies agree on the fact that all things considered equal, those who eat earlier in the day fare better health.

Researchers believe that matching our meals to our body clocks could be an easy dietary adjustment with great therapeutic advantage. “A diet with adequate meal timing and frequency has a pivotal role in glucose control and weight loss,” Dr. Jakubowicz said.

Weight Loss Efforts Are Contagious, Says New Study

Mar 30 by Ewcopywriting Leave a Comment

While it may not be entirely fair to blame an expanding waistline on our partners, there is growing evidence suggesting that our lifestyle choices have a domino effect on those who we share our lives with. With this in mind, a group of researchers asked themselves, “are weight loss efforts contagious in couples outside of highly-structured clinical settings?” The results of their study, recently published in the medical journal Obesity, add further supporting evidence to the idea that our diets have a ripple effect on those closest to us.

According to the lead author of the study, Professor Amy Gorin of the University of Connecticut, “how we change our eating and exercise habits can affect others in both positive and negative ways. On the positive side, spouses might emulate their partner’s behaviors and join them in counting calories, weighing themselves more often, and eating lower-fat foods.”

Study Finds Weight Loss Efforts Contagious in Couples

Mounting evidence points to the fact that our weight may be tied to the people we surround ourselves with, but much of this supporting research was conducted within highly clinical settings or is based upon second-hand self-reporting. Seeking to conduct a more controlled trial in a real-world setting, researchers from the University of Connecticut, in partnership with Weight Watchers International, recently set out to study the viral nature of dieting among couples.

130 couples were divided into two groups and studied for six months. In the first group, one partner from each couple joined a weight loss program with access to counseling and online tools. In the second group, one partner from each couple was given a handout that contained advice about healthy diet, exercise, and weight management strategies. The aim of the study was to examine whether an individual’s participation in a weight management program had a ripple effect on untreated spouses.

Researchers found that the partners from each group who were not participating in a weight loss program or who had not been given weight management literature lost weight alongside their significant others. It was discovered that the partners lost weight at about the same rate despite which of the two groups they fell into. These findings remained consistent throughout the study. Also noted was that their weight loss was interdependent upon their significant other, meaning that if the direct participant was struggling with their weight loss goals, the partner of that participant was also affected.

Numerous studies have found weight within couples to be highly interdependent, and the team’s findings seem to echo those of previous studies. The results may help to shed light on related research regarding weight as a social contagion that suggests these effects may even be as far-reaching as our surrounding communities.

Helpful Tips For Maintaining a Healthy Weight

The viral nature of both our good and bad habits means that our journey to health is not a solo one but one shared by our loved ones and our community. Our individual choices have the power to be far-reaching, therefore, we should be mindful of the domino effect those choices have. Here are a few changes you can make to your lifestyle to promote healthier lives for you and your family.

Be Mindful of Your Eating Habits

Instead of blindly counting calories or following the latest fad diet, take steps to actually learn about nutrition and understand why the things on your plate matter. Pay attention that you’re getting proper portions of the right foods. Fruits and vegetables should always make up the majority of your plate, but a well-rounded diet will also include adequate amounts of complex carbohydrates, lean protein and healthy fats.

The science has shown that antioxidants and omega fatty acids play an important role combating fatigue, supporting adrenal function, and repairing the effects of stress on the body, so, be sure to include plenty of antioxidant- and omega-rich foods into your diet. It may also be helpful to supplement a healthy diet and exercise with a natural supplement that supports healthy metabolism.

Be Mindful of When You Eat As Well

According to research, when we eat is as important as what we eat. Our body’s internal circadian rhythms directly influence hormonal secretions and metabolic processes such as appetite, digestion, blood glucose levels, and the metabolism of fat. Evidence suggests that eating more calories later in the day is associated with obesity and points to the notion that there is an optimal ratio of evening-to-morning caloric intake.

Keep Stress Under Control

Many scientists agree that the obesity epidemic in America is largely related to stress and stress-caused overeating. Stress directly impacts our body’s hormonal levels. It’s well-known that hormones such as cortisol and insulin boost the desire for high-fat, highly-sugared or salted foods. Meditation and aromatherapy using essential oils such as bergamot and frankincense are proven methods of reducing anxiety and stress while incorporating adaptogenic herbs into the diet has been shown to repair and prevent the effects of stress upon the body.

Make Sure You’re Properly Hydrated and Well-Rested

It may seem like common sense advice, but it’s all too easy to underestimate the importance of proper amounts of water and sleep to one’s health. The vast majority of the body’s regeneration is done at night while asleep, making adequate sleep critical to metabolic function. Likewise, hydration is just as crucial. The body is comprised mostly of water and every single cell uses water to maintain proper function. Drinking water regularly throughout the day is known to increase metabolism. In fact, upping your water intake to eight glasses a day could possibly help burn up to 20,000 calories per year alone.

The “Man Flu” Myth: Do Men Really Get Sicker Than Women?

Dec 21 by Ewcopywriting Leave a Comment

In general, men are often perceived as being the physically stronger (and thus possibly healthier) gender. However, their response to infectious illness appears to be an exception to the rule. Many people over time have noted that men subjectively report worse symptoms from colds, cases of the flu and other illnesses. The same illness that most women will work through can leave men bed-ridden for days. Is there a difference in the immune systems of the sexes? A new study has weighed in on the man flu and appears to have surprising results.

Do Men Really Get Sicker?

Many sitcom episodes have been written about the different response that men and women have on average to colds and illnesses. However, it is not humorous for many couples. This is a very real source of tension for many couples, particularly when both are ill and the woman is left with the majority of household duties while the man stays in bed. Dr. Kyle Sue decided to look at this issue more closely to determine if there is a biological cause.

Dr. Sue found several studies indicating a difference in the immune systems of men and women. Women have a greater response to the flu shot and report more side effects, which suggests a stronger immune system. They also are less likely to be hospitalized for influenza and other infectious diseases according to a study in Hong Kong. Last, men subjectively report worse symptoms than women—which is unsurprising to many. The study’s authors concluded rather controversially that many men simply need more care and nurturing when they are ill.

Differences in the Male and Female Immune System

Although this study has been a source of amusement for many people, there appear to be very real differences between male and female immune systems. Studies on mice have found that female immune systems are indeed more responsive than male ones. While this leaves women at a higher risk of autoimmune disease, it also can give them additional protection against bacteria and viruses.

In addition, testosterone appears to work to suppress the immune system. Men with higher testosterone levels overall have less immunity after vaccinations. Testosterone is the primary hormone associated with male traits, so this factor alone may have a significant impact on how often men get sick as well as the severity of their symptoms. In addition, estradiol, an equivalent female hormone, appears to act instead to stimulate the immune system and keep women from getting sick as often.

Is the Man Flu a Myth?

Dr. Sue of the recent study on male immunity feels that men’s notorious behavior when ill may have an evolutionary origin. Because men traditionally hunted, being even mildly ill could be life-threatening. Staying in bed and seeking pampering and care from one’s partner might have saved many lives. He argues that men need this nurturing so they can heal and get back to their duties more quickly.

Although many women obviously feel that the man cold or flu is a myth, there is nothing wrong with providing loving care for a partner when they are ill. If men can also take the time to pamper sick girlfriends and wives, many couples will be happier indeed. More studies will need to be performed to determine if there are truly meaningful differences in female and male immune systems, but the current research is interesting indeed.

Keeping High Immunity in Cold and Flu Season

Regardless of your gender, there are several ways that you can prevent illness this winter. Consider incorporating the following habits into your life:

Wash hands often to keep germs on surfaces from causing illness.
Avoid putting your hands near your face where germs can easily enter the body.
Take a multivitamin to help keep your immune system running in peak form.
Avoid sick people and extremely crowded places where contact with viruses may be inevitable.
Spend more time outside to avoid the high concentration of germs in indoor spaces during cold weather months.
Consider taking vitamin C, zinc, and other supplements associated with immunity if you have been exposed to an illness or are feeling under weather.
Stay home when you are sick or wear a face mask to avoid spreading your own illnesses.
Get plenty of restorative sleep.

There is no way to know if men truly are hit harder by infectious illnesses than the women in their lives. However, both sexes should make it a priority to prevent illness and to nurture each other through them. While many men probably could be more functional when they are sick, staying in bed and nurturing yourself is actually the best way to handle a cold or flu.

Seasonal Affective Disorder (SAD): How Changing Seasons Can Change Your Mood

Nov 27 by Ewcopywriting Leave a Comment

Seasonal affective disorder (SAD) is a type of depression that comes and goes with the seasons. The most typical pattern for SAD is that symptoms start in the late fall or early winter and go away with the arrival of spring. It is also possible for someone to experience seasonal affective disorder in a summer pattern, though this is quite rare.

In previous decades, seasonal affective disorder was considered a completely separate condition than major depressive disorder. However, professionals now consider it to simply be a subset of major depressive disorder, with a seasonal aspect attached.

In order to be diagnosed with SAD, you have to meet the full criteria for clinical depression, you must only experience the depression during a particular season and it must occur for a minimum of two years. If you are experiencing several of the following symptoms, you may meet the diagnostic criteria for a major depressive episode:

anxiety
changes in appetite or weight
difficulty concentrating
feeling hopeless
feeling sad
feeling worthless
feelings of guilt
irritability
lack of energy
lethargy or sluggishness
losing interest in activities you once enjoyed
sleep disturbances
thoughts of death or suicide
symptoms must be present across most days and situations

There are certain risk factors for seasonal affective disorder. Women are four times as likely to be diagnosed with seasonal affective disorder. Those who live far from the equator—whether far north or far south—are many times more likely to suffer from this condition. For example, whereas only 1 percent of Florida residents experience seasonal affective disorder, 9 percent of Alaska residents do. Seasonal affective disorder is most commonly diagnosed in adolescents and young adults, which may indicate that younger age is a risk factor, though it may also be that older adults are less likely to seek out diagnosis and help for this disorder. Lastly, a family history of seasonal affective disorder, major depression and possibly other psychiatric illnesses may raise your risk of developing seasonal affective disorder yourself.

Why Does SAD Occur?

There are several factors that contribute to depression in the darker months of the year (the causes of summertime depression are much less understood). Serotonin is a neurotransmitter highly responsible for maintaining a normal mood; production of this chemical is partly triggered by sunlight exposure. Since there is much less sunlight during the fall and winter, serotonin levels can plummet. Less sunlight also means less vitamin D production; a lack of this nutrient has been highly linked to depression and mood.

Melatonin is another neurotransmitter—its presence promotes mental and physical sleepiness, which is important for falling asleep at night. Melatonin begins to be secreted once the sun goes down; its release is triggered by darkness. When the world around you is dark all the time, melatonin may be released at inappropriate times, leading to lethargy and lack of concentration, which are integral symptoms of depression for many people.

In the fall and winter, the generalized darkness of the outside world can have a negative effect on brain chemistry, causing depression. The cold and gloomy weather can also drive many people to stay inside. Though it may feel cozy to stay at home in the winter, the downside of this is that it could lead to social isolation. Social isolation may be a contributing factor for wintertime depression for some sufferers.

How Can SAD Be Treated?

There are many possible angles to take when it comes to treating seasonal depression. The mainstays of treatment are medication to help re-balance brain chemistry, and specialized psychotherapy for seasonal depression. Therapy is great for helping the patient learn to identify and change negative thoughts and behaviors that perpetuate depression, learn healthy ways to cope with depression and learn how to manage stress.

The principal aspect of treating seasonal affective disorder, that isn’t used to treat conventional depression, is light therapy. The purpose of light therapy is to mimic natural outdoor light to replace the sunlight lost during winter. This treatment has been used for seasonal depression since the 1980s. Traditional light therapy consists of sitting in front of a specially-made bright light for 20 to 60 minutes, usually within the first hour of waking up in the morning.

A common complaint of people who use light therapy is that they do not always have time to sit in front of the light every single morning. To make light therapy more flexible and convenient, a number of companies have developed special light-emitting glasses. With these special glasses, the wearer can continue to carry out everyday tasks while receiving therapeutical doses of light that does not affect the quality of vision.

In addition to these treatments, another great addition to a seasonal depression treatment plan is taking a supplement that contains vitamin D, which has been shown in research to help relieve depressive symptoms. Lastly, an important habit for sufferers of any type of depression to develop is exercise. Research shows that regular exercise can be as effective as medication or psychotherapy. Even just 30 minutes of aerobic exercise three times a week can make a big difference. Exercise relieves depression because it releases endorphins, regulates the circadian rhythm, reduces stress, increases light exposure if done outside and can help improve self-esteem.