Back Clinic Oxidative Stress Chiropractic and Functional Medicine Team. Oxidative stress is defined as a disturbance in the balance between the production of reactive oxygen (free radicals) and antioxidant defenses. In other words, it is an imbalance between the production of free radicals and the body’s ability to counteract or detoxify the harmful effects through neutralization by antioxidants. Oxidative stress leads to many pathophysiological conditions in the body. These include neurodegenerative diseases, i.e., Parkinson’s disease, Alzheimer’s disease, gene mutations, cancers, chronic fatigue syndrome, fragile X syndrome, heart and blood vessel disorders, atherosclerosis, heart failure, heart attack, and inflammatory diseases. Oxidation happens under a number of circumstances:
the cells use glucose to make energy
the immune system is fighting off bacteria and creating inflammation
the bodies detoxify pollutants, pesticides, and cigarette smoke
There are millions of processes taking place in our bodies at any given time that can result in oxidation. Here are a few symptoms:
Memory loss and or brain fog
Muscle and or joint pain
Wrinkles along with grey hair
Headaches and sensitivity to noise
Susceptibility to infections
Choosing organic foods and avoiding toxins in your environment makes a big difference. This, along with reducing stress, can be beneficial in decreasing oxidation.
Dr. Alex Jimenez, D.C., presents how chronic stress can impact the body and how it is correlated with inflammation in this 2-part series. Part 1 examined how stress correlates with various symptoms affecting the body’s gene levels. Part 2 looks at how inflammation and chronic stress correlate with the various factors that can lead to physical development. We refer our patients to certified medical providers who provide available treatments for many individuals suffering from chronic stress associated with the cardiovascular, endocrine, and immune systems affecting the body and developing inflammation. We encourage each of our patients by mentioning them to associated medical providers based on their analysis appropriately. We understand that education is a delightful way when asking our providers questions at the patient’s request and understanding. Dr. Jimenez, D.C., only uses this information as an educational service. Disclaimer
How Stress Can Impact Us?
Dr. Alex Jimenez, D.C., presents: Stress can create many emotions that can hugely impact many of us. Whether it is anger, frustration, or sadness, stress can make anyone reach a breaking point and cause underlying conditions that can develop into cardiovascular issues. So those people with the highest level of anger, when you look at the cardiovascular literature, have the least probability of survival. Anger is a bad player. Anger causes arrhythmia. This study looked at, now that we have people with ICDs and defibrillators, we can monitor these things. And we see that anger can trigger ventricular arrhythmias in patients. And it’s easy now to follow, with some of our technology.
Anger has been linked to episodes of atrial fibrillation. When you think about it, it’s adrenaline outpouring into the body and causing coronary constriction. It’s increasing the heart rate. All of these things can lead to arrhythmia. And it doesn’t have to be AFib. It can be APCs and VPCs. Now, some very interesting research has come out about telomerase and telomeres. Telomeres are little caps on the chromosomes, and telomerase is the enzyme linked to telomere formation. And now, we can understand through the language of science, and we’re starting to use technology and use science in a way that we could never do before to understand the impact of stress on telomeres and telomerase enzymes.
The Factors That Lead Up To Chronic Stress
Dr. Alex Jimenez, D.C., presents: So one of the key people to study this is the Nobel Prize-winning, Dr. Elizabeth Blackburn. And what she said is that this is a conclusion, and we’ll come back to some of her other studies. She tells us that the telomeres of babies from women in utero had a lot of stress or were even shorter in young adulthood compared to mothers who did not have the same stressful situations. Maternal psychological stress during pregnancy may exert a programming effect on the developing telomere biology system that is already apparent at birth as reflected by the setting of newborn leukocyte telemetry length. So children can come in imprinted, and even if they do, this can be transformed.
What about racial discrimination these boxes here show high racial discrimination leading to low telomere length, which most of us have ever thought about. So, shorter telomere length leads to an increased risk of cancer and overall mortality. Cancer incidence rates are 22.5 per 1000 person-years in the shortest telomere group, verse 14.2 in the middle group, and 5.1 in the longest telomere group. Shorter telomeres can lead to instability of the chromosome and result in cancer formation. So, now we understand, through the language of science, the impact of stress on the telomerase enzyme and the telomere length. According to Dr. Elizabeth Blackburn, 58 premenopausal women were caregivers of their chronically ill children verse women who had healthy children. The women were asked how they perceive stress in their lives and whether it impacts their health by affecting their cellular aging.
That was the question of the study as they looked at telomere length and telomerase enzyme, and this is what they found. Now, the keyword here is perceived. We are not to judge each other’s stress. Stress is personal, and some of our responses may be genetic. For example, someone who has homozygous comps with a sluggish gene may have much more anxiety than someone who doesn’t have this genetic polymorphism. Someone who has an MAOA in an MAOB may have more anxiety than someone who doesn’t have that genetic polymorphism. So there is a genetic component to our response, but what she found was perceived psychological stress. And the number of years caring for chronically ill children was associated with shorter telomere length and less telomerase activity, providing the first indication that stress can impact telomere maintenance and longevity.
How To Transform Our Stress Response?
Dr. Alex Jimenez, D.C., presents: That’s powerful, and many healthcare providers are under some form of stress. And the question is, what can we do to transform our response? Framingham also looked at depression and identified clinical depression as a bigger risk for cardiovascular events and poor outcomes than smoking, diabetes, high LDL, and low HDL, which is crazy because we spend all of our time on these things. Yet, we don’t spend much time dealing with the emotional aspects of vascular disease. This is affected depression, inventory, a simple screening test for depression, looking at people with high levels of depression versus low levels of depression. And you can see that as you go from the low to the highest level, as you work your way through, the chance of survival becomes less.
And many of us have our theories as to why this occurs. And is it because if we are depressed, we don’t say, “Oh, I’m going to eat some brussels sprouts, and I’m going to take those B vitamins, and I’m going to go out and exercise, and I’m going to do some meditation.” So post-MI independent risk factor for an event is depression. Our mindset regarding depression makes us incapable of functioning normally and can make our bodies develop issues that affect our vital organs, muscles, and joints. So, depression is a big player, as 75% of post-MI deaths are related to depression, right? So looking at patients, now, you have to ask the question: Is it the depression causing the problem, or is it the cytokine sickness that’s already led to the heart disease causing the depression? We have to factor all of this in.
And yet another study looked at over 4,000 people with no coronary disease at baseline. For every increase of five points on the depression scale, that increased risk by 15%. And those with the highest depression scores had a 40% higher coronary artery disease rate and a 60% higher death rate. So mostly everyone thinks it’s a cytokine sickness that leads to MI, vascular disease, and depression. And then, of course, when you have an event, and you come out with a whole host of issues around it, we know that people who are depressed have a twofold increase in mortality, a fivefold increase in death after a heart attack, and poor outcomes with surgery. It’s like this, what came first, the chicken or the egg?
How Depression Is Linked With Chronic Stress?
Dr. Alex Jimenez, D.C., presents: Every surgeon knows this. They don’t want to do surgery on depressed people. They know the outcome is not good, and of course, they are less likely to follow through on all of our great functional medicine recommendations. So what are some of the mechanisms of autonomic dysfunction have been evaluated heart rate variability and low levels of omega-3s, which have a profound effect on the brain, and low levels of vitamin D. There are those inflammatory cytokines we talked about not getting restorative sleep, and many of our heart patients do have apnea. And remember, don’t just think it’s the heavyset heart patients with thick short necks; it can be quite deceiving. And it’s really important to look at the structure of the face and, of course, social connection, which is the secret sauce. So is autonomic dysfunction a mechanism? One study looked at heart rate variability in people with a recent MI, and they looked at over 300 people with depression and those without depression. They found that four heart rate variability indices will lower in people with depression.
Gut Inflammation & Chronic Stress
Dr. Alex Jimenez, D.C., presents: So here are two groups of people having a heart attack and heart rate variability, rising to the top as a possible etiology. One of the many things that can also affect chronic stress in the body is how the gut microbiome plays its part in oxidative stress. The gut is everything, and many heart patients laugh because they would ask their cardiologists, “Why do you care about my gut microbiome? Why would this affect my heart?” Well, all that gut inflammation is causing cytokine sickness. And what a lot of us have forgotten since medical school is that many of our neurotransmitters come from the gut. So chronic inflammation and exposure to inflammatory cytokines appear to lead to alterations in dopamine function and the basal ganglia, reflected by depression, fatigue, and psychomotor slowing. So we can’t emphasize the role of inflammation and depression enough if we take a look at acute coronary syndrome and depression, which was associated with higher markers for inflammation, more elevated CRP, lower HS, lower heart rate variability, and something that never gets checked in the hospital, which is nutrition deficiencies.
And in this case, they looked at omega-3s and vitamin D levels, so at a minimum, an omega-3 check and a vitamin D level are warranted in all of our patients. And certainly, if you can get a full diagnosis for stress-induced inflammation. Another condition you must look at when it comes to stress-induced inflammation is osteoporosis in the joints. Many people with osteoporosis will have muscle loss, immune dysfunction, fat around the midline, and high blood sugar are associated with aging, and it can come from elevated cortisol levels in the body.
High cortisol heart disease risks are two times higher in people taking high doses of steroids. Small amounts of steroids don’t have the same risk, so it is not as big a deal. Of course, we try to get our patients off of steroids. But the point here is that cortisol is a stress hormone and is a stress hormone that raises blood pressure and puts weight on the midline, makes us diabetic, causes insulin resistance, and the list is endless. So, cortisol’s a big player, and when it comes to functional medicine, we have to look at the various tests that pertain to elevated levels of cortisol like food sensitivity, a 3-day stool valve, a nutra-valve, and an adrenal stress index test to look at what is going on with the patients. When there is a heightened sympathetic nervous system and high cortisol, we discussed everything from coagulopathy to decreased heart rate variability, central obesity, diabetes, and hypertension.
Parental Relationships & Chronic Stress
Dr. Alex Jimenez, D.C., presents: And turning on the renin-angiotensin system it’s all linked to stress. Let’s look at this study that looked at 126 Harvard Medical students, and they were followed for 35 years, a long research. And they said, what’s the incidence of significant illness, heart disease, cancer, hypertension? And they asked these students very simple questions, what was your relationship with your mom and your dad? Was it very close? Was it warm and friendly? Was it tolerant? Was it strained and cold? This is what they found. They found that if the students identified their relationship with their parents as strained 100% incidence of significant health risk. Thirty-five years later, if they said it was warm and close, the results cut that percentage in half. And it would help if you thought about what it is and what can explain this, and you’ll see how adverse childhood experiences make us sick in a few minutes and how we learn our coping skills from our parents.
Dr. Alex Jimenez, D.C., presents: Our spiritual tradition comes from our parents often. Our parents are the ones who frequently teach us how to get angry or how to resolve conflict. So our parents have had a profound effect on us. And when you think about that, our connection is also not very surprising. This is a 35-year follow-up study.
Chronic stress can lead to multiple issues that can correlate to illness and dysfunction in the muscles and joints. It can affect the gut system and lead to inflammation if it is not taken care of immediately. So when it comes to the impact of stress affecting our daily lives, it can be numerous factors, from chronic conditions to family history. Eating nutritious foods high in antioxidants, exercising, practicing mindfulness, and going to daily treatments can lower the effects of chronic stress and reduce the associated symptoms that overlap and cause pain to the body. We can continue with our health and wellness journey pain-free by utilizing various ways to lower chronic stress in our bodies.
Dr. Alex Jimenez, D.C., presents how stress can impact many individuals and correlate with many conditions in the body in this 2-part series. We refer our patients to certified medical providers who provide multiple available treatments for many people suffering from hypertension associated with the cardiovascular, endocrine, and immune systems affecting the body. We encourage each of our patients by mentioning them to associated medical providers based on their analysis appropriately. We understand that education is a delightful way when asking our providers questions at the patient’s request and understanding. Dr. Jimenez, D.C., only uses this information as an educational service. Disclaimer
How Stress Impacts the Body
Dr. Alex Jimenez, D.C., presents: Now everyone responds to changes in the environment differently. When it comes to many individuals doing everyday activities from working at their job, opening on the weekends, traffic jams, taking exams, or preparing for a big speech, the body goes through a constant state of hyperreactive to a stage of emotional, mental exhaustion that leaves the individual to be exhausted and stressed out. And the key is to recognize this before it happens, as we see this impact of stress on our patients and ourselves. And the first thing to realize is what the initiating event is causing this impact.
Whatever the initiating event, the most important part is our perception of the event. What does it mean to us? Is it our perception? When the body goes through this initiating event, it can cause the perception to lead to the response and the effect on our body. So perception is everything as we talk about stress and the stress response. Now, we have over 1400 chemical reactions that occur in the body. So for this talk’s purpose, we’ll discuss the three key ones: adrenaline and neuro-adrenaline, aldosterone, and of course, cortisol.
And why are these important? Because every one of these has a huge impact on cardiovascular disease. Now, in the 1990s, many doctors were starting to understand the effect of stress on the physical body. And what happens to people when their HPA-axis signals that they are under threat and start flooding their bodies with stress hormones? Well, we see enhanced coagulation. We see a shift in the renin and angiotensin system. It revs up. We see weight gain in people and insulin resistance. What a lot of people don’t realize is that lipids become abnormal with stress. Almost every one of our patients knows that tachycardia and arrhythmia occur when our adrenaline is flowing, and our blood pressure increases. Now, think about this through the language of medicine.
Around the 1990s, doctors were giving aspirin and Plavix at the time for coagulation. We continue to provide ACEs and ARBs to our patients. The impact of cortisol causes weight gain and insulin resistance. We give statins; we give metformin. We provide beta blockers for that, tachycardia, and calcium blockers for that high blood pressure. So every single hormone that gets turned on with stress, we have a drug that we’re using to balance that. And quite frankly, for years, we talked about how good beta blockers were for the heart. Well, when you think about that, beta blockers do block adrenaline. So when doctors look at this, they begin to think, “Well, maybe we need to medicate and meditate, right? We’re using all these drugs, but we may need to look at other ways to transform the stress response.”
What is Vasoconstriction?
Dr. Alex Jimenez, D.C., presents: We won’t read every one of these symptoms because there are so many, but it all comes down to the same thing. Stress. We have to think of someone who’s in an auto accident, for example, and that person is bleeding. So the body is beautiful in that it puts together a way to stop the individual from bleeding or vasoconstriction. Vasoconstriction is constructing these blood vessels and making the platelets sticky so they form a clot, and the blood can stop. This increases the cardiac output by raising the heart rate and increases aldosterone, which causes salt and water retention to raise the blood pressure. So for someone in a medical emergency, like an accident, bleeding, or losing volume, this is the beauty of the human body. But unfortunately, we see people living this way, literally 24/7. So we know the vasoconstriction and the platelet stickiness, and we see increases in markers for inflammation, homocysteine, CRP, and fibrinogen, all of which increase cardiovascular risk.
We see the impact of cortisol, not only raising blood pressure, not only causing diabetes and insulin resistance, but also depositing abdominal fat around the midline. And then, as you’ll see in a few minutes, there are links between stressful events and arrhythmias like atrial fibrillation and even ventricular fibrillation. For the first time in medicine, in cardiology, we have a syndrome called takosubo cardiomyopathy, which is affectionately called broken heart syndrome. And this is a syndrome in which the myocardium becomes acutely stunned to the point of causing severe left ventricular function or dysfunction. And usually, this is triggered by bad news and an emotionally stressful event. It looks like someone needs a heart transplant. So when we think about the old Framingham risk factors, we say, which of these are impacted by stress?
Symptoms of Stress
Dr. Alex Jimenez, D.C., presents: People have all sorts of maladaptive behaviors to stress, whether 20 friends in this pack of cigarettes, eating this Cinnabon because it makes me feel good right now, or all the cortisol will make me fat and diabetic. Lipids go up under stress; blood pressure goes up under stress. So every one of these risk factors is impacted by stress hormones. And, of course, we know that with the turning on of the RAS system or the renin-angiotensin system, we always see a worsening in heart failure. And this is very much described in the literature. And, for those of you who may work in the emergency room, ask your patients what they were doing before coming in with their episode of congestive heart failure or chest pain. And you’re going to hear stories like, I was watching a bad movie, or I was watching a war movie, or I got upset over the football game, or something like that.
We’ll talk about heart rate variability, which gets impacted by stress. And, of course, stress affects our ability to resist infections. And we know that people are under stress when they’re vaccinated. For example, Cleco lasers work but don’t produce antibodies to the vaccine when they’re under stress. And, of course, as you’ll see in a minute, severe stress can cause sudden cardiac death, MI, and so on. So it is a bad player that’s overlooked. And for many of our patients, stress drives the train. So when we’re talking about eating brussels sprouts and cauliflower and, you know, lots of green leafy vegetables, and someone is under so much stress that they’re trying to figure out, “How am I going to get through the day?” They’re not hearing any of the other things that we’re recommending.
So, chronic stress and affective disorders, whether depression, anxiety, or panic, put our foot on the accelerator and rev up the sympathetic nervous system. We know that the same things we see with aging, as you’ll see in a minute, are linked to increased levels of stress hormones, especially cortisol. So whether it’s osteoporosis, decreased bone density, endothelial dysfunction, platelet activation, hypertension, central obesity, or insulin resistance, this comes from a stress response. And we have to have a plan for our patients on how to handle this. American Institute of Stress says that 75 to 90% of all healthcare provider visits result from stress-related disorders. And that’s way too high, but by looking at the patients and where they were coming in with, they tell their stories to their doctors. The results are the same; it doesn’t matter whether it was headaches, muscle tension, angina, arrhythmia, or irritable bowel; it almost always had some stress trigger.
Acute & Chronic Stress
Dr. Alex Jimenez, D.C., presents: There’s a difference between acute and chronic stress with our perception and social connection. Even though we gain some strength from a higher power, stress can impact anyone, and most of us might not be able to handle it well. So a great study was done many years ago by Dr. Ray and Holmes that stated, 50 years ago, put together a method for quantifying life-changing events. So let’s look at some areas, such as life-changing events. How do life-changing events and how do they rank? Which are the big ones, and which are the little ones?
And how does that ranking lead to major medical problems like cancer, heart attack, and sudden death in the future? So they looked at 43 life-changing events, ranked them originally, and re-ranked them in the 1990s. And some of them remained the same. They gave an adjustment score to the event, and then they looked at numbers that would be linked to major illness. So, for example, a life-changing event. Number one, 100 life-changing units, is a death of a spouse. Anyone could relate to that. Divorce was number two, separation number three, and the end of a close family member. But also noticed that some things got ranked that are, you might not equate with, being a major life-changing event that can impact a stress response like marriage or retirement.
Dr. Alex Jimenez, D.C., presents: So it wasn’t the actual single event that made the difference. It was the adding up of events. And what they found after looking at 67 physicians was if you had a life-changing unit score of somewhere between zero and one 50, not a big deal, no real major illness, but once you hit that 300 mark, there was a 50% chance of major illness. So this timeline of events in the patient’s life. We want to know what was going on in their life when their symptoms started and then bring it back earlier to understand the environment in which this individual was living. The impact of stress can make many individuals develop chronic conditions and mask other symptoms that can lead to muscle and joint pain. In part 2, we will dive in more about how the impact of stress affects a person’s body and health.
Dr. Alex Jimenez, D.C., presents how hypertension affects the human body and some causes that can increase hypertension in many individuals in this 2-part series. We refer our patients to certified medical providers who provide multiple available treatments for many individuals suffering from hypertension associated with the cardiovascular and immune systems affecting the body. We encourage each of our patients by mentioning them to associated medical providers based on their analysis appropriately. We understand that education is a delightful way when asking our providers questions at the patient’s request and understanding. Dr. Jimenez, D.C., only makes use of this information as an educational service. Disclaimer
How To Look For Hypertension
Dr. Alex Jimenez, D.C., presents: Let’s go back to the decision tree so you can begin to think about how you will apply the go-to-it model in functional medicine to hypertension and how you will start better assessing somebody with hypertension rather than telling them that their blood pressure is elevated. Is the body influenced by inflammation, oxidative stress, or immune response? Is it affecting endothelial function or vascular smooth muscle from those three categories of reactions, inflammation, oxidative stress, or immune response? Do we choose a diuretic calcium channel blocker or an ACE inhibitor? And so to do that, it’s really important in our gather section. Taking the medical history and the timeline of their hypertension, you get a clue about the organ damage to the questionnaires. You’re looking at their anthropometrics.
This includes the following questions:
What are the inflammatory markers?
What are the biomarkers and clinical indicators?
Those are outlined through the clinical decision tree. And already just doing that, you’re going to expand and fine-tune your lens on what you might see in your hypertensive patient. Let’s add to the timeline when does hypertension begin? The timeframe of hypertension begins actually in prenatally. It’s important to ask your patient if they were early or large educational age. Was their mother stressed? Were they born early or premature? Was there nutritional stress in their pregnancy? If they know that, you can have two people with the same kidney size, but the person who didn’t have enough protein during pregnancy can have up to 40% less glomeruli. Knowing that will change how you adjust the medication decades later if you know they possibly have 40% less glomeruli.
The Timeline For Blood Pressure
Dr. Alex Jimenez, D.C., presents: So it’s important to take the timeline of their blood pressure. Then it’s also important to recognize what is happening when we begin to organize and collect data through the biomarkers; the basic biomarkers will give you clues about whether they have issues with insulin lipids, whether they have problems with vascular reactivity, autonomic nervous system balance, imbalance, coagulation, or immune toxin effects. So this is a reasonable thing to print off because, in your hypertensive patient, this is through just the biomarkers you can begin to get a clue as to what areas of dysfunction affect inflammation, oxidative stress, and immune response and how these biomarkers reflect that information for you. This is very reasonable to have in front of you to help change your thoughts about hypertension and also enables you to refine some of the characteristics of the person on the other side of your stethoscope in a more personalized, precise way.
But let’s start at the very beginning. Does your patient have high blood pressure? We know that depending on the end organ effects of their comorbidities, you may run someone a slightly higher blood pressure if you have a profusion issue in the brain and the kidneys or the heart, but some guidelines are there. Our 2017 American Heart Association guidelines for blood pressure categories are listed here. They’ve waxed and waned back and forth over the last couple of decades, but this is very clear. Having elevated blood pressure, anything above 120, really shifted how many people we start seeing or considering addressing the root causes of their blood pressure. So we will come back to this, especially in the case to help us look at how we categorize people with blood pressure issues.
The Criteria To Mesure Blood Pressure
Dr. Alex Jimenez, D.C., presents: What is the first step? It’s how do you have the blood pressure taken in your patient? Do they monitor it at home? Do they bring those numbers to you? How do you monitor blood pressure in your clinic? How do you get accurate readings in your clinic? Here are the criteria to accurately measure blood pressure and the questions to consider whether you’re doing all these.
Do you ask your patient whether they’ve had caffeine in the last hour?
Whether they’ve smoked in the previous hour?
Were they exposed to smoke in the last hour?
Is the place where you’re taking blood pressure warm and quiet?
Are they sitting with their back supported in a chair with their feet on the ground?
Do you use the roll-around side table to rest your arm at the heart level?
Are they sitting at the exam table with their feet dangling, and a nurse aide elevates their arm and puts in their axillary fold to hold their arm there?
Are their feet on the ground?
Have they sat there for five minutes?
Have they exercised in the previous 30 minutes?
You may have systolic blood pressure if everything is in the criteria. Here’s the challenge. There are 10 to 15 millimeters of mercury higher when it comes to sitting and taking blood pressure. What about the cuff size? We know last century; most adults had an upper arm circumference of fewer than 33 centimeters. Over 61% of people now have an upper arm circumference greater than 33 centimeters. So the size of the cuff is different for around 60% of your adult patients, depending on your population. So you have to use a large cuff. So take a look at how blood pressure is collected in your office. Let’s say the blood pressure is elevated in your patients; then we have to ask, is it normal? Great.
The Different Types Of Hypertension
Dr. Alex Jimenez, D.C., presents: Is it elevated because of white-coat hypertension? Do they have normal blood pressure, elevated outside the clinic, or masked hypertension? Or do they just have sustained hypertension which is a challenge? We’ll talk about that. So when you interpret, it is also important to consider ambulatory blood pressure monitoring. So if you have somebody who’s hypertensive and don’t know whether the blood pressure goes down and you’re trying to figure out whether they have sustained hypertension, you can use 24-hour blood pressure monitoring. The mean daytime blood pressure above 130 over 80 is hypertensive the mean nighttime blood pressure above 110 over 65 is hypertensive. So why is this important? The average blood pressure dips to around 15% at night because of the issue with blood pressure dipping. Failure to have blood pressure drop while you sleep at night could develop problems that can affect a person throughout the day.
If your patient sleeps at night, it should drop about 15% when they sleep. If they have non-dipping blood pressure, it is associated with comorbidities. What are some of those comorbidities in non-dipping blood pressure? Some of the conditions correlated with non-dipping blood pressure include:
Congestive Heart Disease
Congestive Heart Failure
Chronic Renal Failure
Silent Cerebral Infractions
Co-morbidities Associated With Non-Blood Pressure
Dr. Alex Jimenez, D.C., presents: These are the comorbidities associated with non-blood pressure. All of us agree that elevated blood pressure is not necessarily good in all those conditions. So when you look at different people groups or other comorbidities, non-dipping blood pressure is most commonly associated with sodium-sensitive folks, people who have renal insufficiency, people who have diabetes, people who have left ventricular hypertrophy, people who have refractory hypertension or autonomic nervous system dysfunction and finally, sleep apnea. So, non-dipping blood pressure increases your association with subclinical cardiac damage. Okay, Reverse dipping means you are more hypertensive at night and is more ascent associated than during the day is more related to hemorrhagic stroke. And if you have somebody with nocturnal hypertension, you have to start thinking about things like the carotid arteries and increased carotid, internal medial thickness. You start thinking about left ventricular hypertrophy and may see it on EKG. Here’s what we know about nocturnal hypertension. Nocturnal hypertension is a nighttime blood pressure greater than 120 over 70. It is associated with greater predictability of cardiovascular morbidity and mortality.
If you have nocturnal hypertension, it increases your risk of mortality from cardiovascular disease by 29 to 38%. We must know what’s happening at night when we sleep, right? Well, what’s another refinement? Another refinement is recognizing that resting blood pressure is controlled by your renin-angiotensin system. Waking blood pressure is controlled by your sympathetic nervous system. So let’s talk about how their renal angiotensin system drives their nighttime hypertension, and you think about what medication they’re taking. You might change the medication dosing to nighttime. Well, studies have shown that if you have nighttime hypertension and are a non-dipper, it’s best to take your ACE inhibitors, ARBs, calcium channel blockers, and certain beta blockers at night before bed. But it makes sense that you wouldn’t move your diuretics to nighttime, or you will have a disruptive sleep.
Addressing Daytime & Nighttime Blood Pressure
Dr. Alex Jimenez, D.C., presents: So if we don’t address daytime and nighttime blood pressure, we have to consider the effect of blood pressure load. What is your average daytime blood pressure and your moderate sleeping blood pressure is. We know that blood pressure load in young adults is hypertensive only about 9% of the time. So meaning the systolic load is about 9% versus in the elderly, about 80% of the blood pressure load is systolic. And so when you have a higher systolic load, you have more complications and end-organ damage. So what we’re talking about is helping identify your patient with hypertension; what is their timeline? What is their phenotype? Are they only hypertensive during the day, or they’re hypertensive at night also? We have to look at what helps balance that.
Here’s the other point, only about 3.5% of people with hypertension do it have a genetic cause. Only 3.5% of people their genes cause hypertension. The power is at the bottom of the matrix and recognizing these patterns, right? So you look at exercise, sleep, diet, stress, and relationships. So we know that these four autonomic balances help determine blood pressure. We will examine the renal angiotensin system, plasma volume where they hold onto too much fluid, secondary salt load, and endothelial dysfunction. Abnormalities in any of these can lead to hypertension. We’ve been talking about another one that can lead to hypertension: the link between insulin resistance and hypertension.
This diagrammatically gives you an idea of the physiologic interactions between insulin resistance and hypertension. It affects increasing sympathetic tone and increasing renal-angiotensin system balance. So let’s spend a few minutes on the renin-angiotensin system pathway angiotensinogen down to angiotensin two. We take advantage of these enzymes by giving inhibitors to angiotensin-converting enzymes in our hypertensives patients. Elevated angiotensin two leads to cardiovascular hypertrophy, leads to sympathetic phase constriction, increased blood volume, sodium fluid, retention, and aldosterone release. Can you inquire about your patient biomarkers? Can you ask whether they have elevated renin levels?
Look For The Signs
Dr. Alex Jimenez, D.C., presents: Well, you can. You can check plasma renin activity and aldosterone levels. It’s important to do this if your patient is hypertensive and has never been on medication because this is where nitrous oxide is so important. This is where your endothelial nitric oxide synthase is present. This is where you have sheer and hemodynamic stress. This is where dietary intake of arginine or the environment that affects nitric oxide plays such a role in the health of this layer of endothelia. If you lay it all together somehow, miraculously, or at least in your mind’s eye, it’ll cover six tennis courts in the average adult. It’s a huge surface area. And the things that cause endothelial dysfunction are not new news to people in functional medicine. Increased oxidative stress and inflammation are two things we mentioned that play an effect.
And then, look at some of these other components, your ADMA being elevated and correlated with insulin resistance. It all begins to form together in a matrix that interacts. So you look at one comorbidity in cardiometabolic syndrome, and it affects another comorbidity. You suddenly see the interrelation between them or hyperhomocysteinemia, which is a one-carbon metabolism marker, meaning you’re looking at the adequacy of folate, b12, b6, riboflavin, and that activity of your one-carbon metabolism. So let’s look at some of these emerging risk markers to improve and track in patients with hypertension. Let’s reanalyze ADMA again. ADMA stands for asymmetric dimethyl arginine. Asymmetric, dimethyl arginine is a biomarker of endothelial dysfunction. That molecule inhibits nitric oxide synthase while impairing endothelial function, and in all of the comorbidities associated with cardiometabolic syndrome, ADMA can be elevated.
So, as a quick review, L-arginine is converted to nitric oxide via nitric oxide synthase, and nitric oxide adequacy leads to vasodilation. ADMA blocks this conversion. And if your ADMA levels are elevated and your nitric oxide levels are low, then you have decreased nitric oxide platelet aggregation increases in LDL oxidation. So many things reduce nitric oxide or are associated with lower nitric oxide levels, sleep apnea, low dietary arginine, protein, zinc insufficiency, and smoking.
Everybody deals with stress at some point in their lives. Whether it be a job interview, a huge deadline, a project, or even a test, stress is there to keep the body functioning in each scenario that the body is going through. Stress can help regulate the body’s immune system and help metabolize homeostasis as the body increases its energy throughout the day. When dealing with chronic stress can cause metabolic dysfunction in the body like gut disorders, inflammation, and an increase in blood glucose levels. Chronic stress can also affect a person’s mood and health, eating habits, and sleep quality. Today’s article will look at if stress is a good thing or a bad thing, how it affects the body, and the effects of what chronic stress does to the body. Refer patients to certified, skilled providers specializing in gut treatments for individuals that suffer from autonomic neuropathy. We guide our patients by referring to our associated medical providers based on their examination when it’s appropriate. We find that education is critical for asking insightful questions to our providers. Dr. Alex Jimenez DC provides this information as an educational service only. Disclaimer
Can my insurance cover it? Yes, it may. If you are uncertain, here is the link to all the insurance providers we cover. If you have any questions or concerns, please call Dr. Jimenez at 915-850-0900
Is Having Stress Good Or Bad?
Do you feel anxious all the time? How about feeling headaches that are constantly being a nuisance? Feeling overwhelmed and losing focus or motivation? All these signs are stressful situations that a person is going through. Research studies have defined stress or cortisol as the body’s hormone that provides a variety of effects on different functions in each system. Cortisol is the primary glucocorticoid that is from the adrenal cortex. At the same time, the HPA (hypothalamus-pituitary-adrenal) axis helps regulates the production and secretion of this hormone to the rest of the body. Now cortisol can be beneficial and harmful to the body, depending on the situation a person is in. Additional research studies have mentioned that cortisol begins and affects the brain and the rest of the body as stress in its acute form can cause the body to adapt and survive. The acute responses from cortisol allow neural, cardiovascular, immune, and metabolic function in the body.
How Does It Affect The Body’s Metabolism?
Now cortisol affects the body’s metabolism when controlled in a slow, steady sleep cycle that decreases corticotropin‐releasing hormone (CRH) and increases growth hormone (GH). Research studies have shown that when the adrenal glands secrete cortisol, it starts to have a complex interaction with the hypothalamus and pituitary glands in the nervous and endocrine systems. This causes the adrenal and thyroid function in the body to be closely linked while under the control of the hypothalamus and tropic hormones. The thyroid competes with the adrenal organs for tyrosine. Research studies have found that tyrosine is used to produce cortisol under stress while preventing cognitive function decline that is responsive to physical stress. However, when the body can not produce enough tyrosine, it can cause hypothyroidism and cause the cortisol hormone to become chronic.
An Overview About Stress-Video
Have you experienced headaches that randomly show up out of nowhere? Have you constantly gained weight or lost weight? Do you feel anxious or stressed out always that it is affecting your sleep? These are all signs and symptoms of your cortisol levels turning into their chronic state. The video above shows what stress does to your body and how it can cause unwanted symptoms. When there is chronic stress in the body, the HPA axis (neuro‐endocrine) is imbalanced due to the stress‐mediated activators involved in autoimmune thyroid diseases (AITD). When there is chronic stress in the body, it can cause excessive production of inflammatory compounds in the body can generate IR. The inflammatory substances can damage or inactivate insulin receptors leading to insulin resistance. This then contributes to the breakdown of one or more factors needed to complete the glucose transport process in the body.
The Effects Of Chronic Cortisol In The Body
When there is chronic stress in the body and has not been treated or reduced right away, it can lead to something known as allostatic load. Allostatic load is defined as wear and tear of the body and brain due to chronic overactivity or inactivity of the body systems typically involved in environmental challenges and adaptation. Research studies have shown that allostatic load causes excess secretion of hormones like cortisol and catecholamine to respond to chronic stressors affecting the body. This causes the HPA axis to do one of two things: being overworked or failing to shut off after stressful events causing sleep disturbances. Other issues that chronic stress does to the body can include:
Increased insulin secretion and fat deposition
Altered immune function
Hypothyroidism (adrenal exhaustion)
Sodium and water retention
Loss of REM sleep
Mental and Emotional instability
Increase in cardiovascular risk factors
These symptoms cause the body to become dysfunctional, and research studies have pointed out that various stressors can damage the body. This can make it extremely difficult for a person to cope with stress and alleviate it.
Overall, stress or cortisol is a hormone the body needs to function correctly. Chronic stress in the body from various stressors can cause many metabolic dysfunctions like hypothyroidism, weight gain, insulin resistance, and metabolic syndrome, to name a few. Chronic stress can also cause sleep disorders since the HPA axis is wired up and can seem to calm down the slightest. When people start to find ways of dealing with these various stressors, they can reduce their stress levels back to normal and be stress-free.
McEwen, Bruce S. “Central Effects of Stress Hormones in Health and Disease: Understanding the Protective and Damaging Effects of Stress and Stress Mediators.” European Journal of Pharmacology, U.S. National Library of Medicine, 7 Apr. 2008, www.ncbi.nlm.nih.gov/pmc/articles/PMC2474765/.
Rodriquez, Erik J, et al. “Allostatic Load: Importance, Markers, and Score Determination in Minority and Disparity Populations.” Journal of Urban Health : Bulletin of the New York Academy of Medicine, Springer US, Mar. 2019, www.ncbi.nlm.nih.gov/pmc/articles/PMC6430278/.
As the world is in constant motion, many people have to endure stressful situations affecting their bodies and health. The body needs hormones like cortisol to keep functioning as it affects the immune, nervous, cardiovascular, and musculoskeletal systems, to name a few. Another essential function the body needs is glucose, which requires energy to be in constant motion. Situations that cause the cortisol levels and glucose levels to rise in the body can lead to chronic issues like diabetes and chronic stress. This causes the individual to be miserable and be in a serious situation if it is not controlled right away. Today’s article examines how cortisol and glucose affect the body and the interwoven connection between stress and diabetes. Refer patients to certified, skilled providers specializing in stress management and endocrine treatments for diabetic individuals. We guide our patients by referring to our associated medical providers based on their examination when it’s appropriate. We find that education is critical for asking insightful questions to our providers. Dr. Alex Jimenez DC provides this information as an educational service only. Disclaimer
Can my insurance cover it? Yes, it may. If you are uncertain, here is the link to all the insurance providers we cover. If you have any questions or concerns, please call Dr. Jimenez at 915-850-0900.
How Does Cortisol Affect The Body?
Have you been experiencing sleeping problems at night? What about frequent headaches that are a nuisance throughout the entire day? Or have you noticed excessive weight loss or weight gain around your midsection? Some of these symptoms are signs that your cortisol and glucose levels are high and can affect your body. Cortisol is a hormone produced in the endocrine system and can be beneficial or harmful to the body if it is not regularly checked. Research studies have defined cortisol as one of the prominent glucocorticoids secreted out due to the response of the body’s biochemicals, characterized by the HPA (hypothalamic‐pituitary‐adrenal) axis helps cognitive events. However, when the cortisol levels turn chronic in the body due to circumstances that cause the body to become dysfunctional, it can significantly impact a person and cause an imbalance in the HPA axis. Some of the symptoms that chronic cortisol leads to the body can include:
Increases in visceral “belly” fat
Increased cortisol output
Allergies and Asthma
Poor exercise recovery
Additional information has provided that the presence of cortisol in the body can help increase blood glucose availability to the brain. With cortisol providing organ functionality, the blood glucose provides energy for the body.
How Cortisol & Glucose Work In The Body
Cortisol helps stimulate mass glucose mobilization in the liver, allowing block protein synthesis to push amino acids into sugar for the body. This is known as fatty acid liberation biotransformed into glucose. When this happens, it helps stimulate visceral fat storage if excess glucose is not utilized, thus causing weight gain. Research studies have shown that a lack of cortisol can cause a decrease in hepatic glucose production in the body. This will cause hypoglycemia, where the body doesn’t have enough glucose in its system. Additional research shows that cortisol responds to any stressor that affects a person with low glucose levels but can also become positive after a glucose load. Managing the body’s glucose and cortisol levels can help progress the development of diabetes.
How Cortisol Is Linked With Type 2 Diabetes- Video
Have you experienced stressful situations that cause your muscles to tense up? How about feeling your blood sugar either spiking up or down? Do you feel inflammatory effects all over your body that makes them ache? Stress can cause harmful effects to the body, activating inflammation, increasing sympathetic tone, and reducing glucocorticoid responsiveness. Stress can also be linked to diabetes, as the video above shows how the stress hormone cortisol is linked with type 2 diabetes. Research studies have mentioned that cortisol can become negatively associated with the mechanics of insulin resistance, increasing the beta-cell function and increasing the insulin released in the body. This can become dangerous for many individuals that have pre-existing diabetes and have been dealing with stress constantly.
The Interwoven Connection Between Stress & Diabetes
The interwoven connection between stress and diabetes is shown as research studies have found that the pathophysiology of anxiety and diabetes has increased insulin resistance risk for the body. When a person is dealing with chronic stress, it can cause them to have many issues like:
Diminished cognition and mood
Low energy throughout the day
When this happens, the body is at a high risk of developing insulin resistance and type 2 diabetes. Research studies have mentioned that type 2 diabetes is characterized by insulin resistance and beta-cell dysfunction. The glucocorticoid in the body can become excessive to affect the cells, causing dysfunctionality. Additional research studies have shown that any perceived stress can become a vital risk factor that not only affects the body, like hypertension, BMI (body mass index), or diet quality but can cause a rise in type 2 diabetes. When individuals find ways to lower their chronic stress, it can help manage their glucose levels from reaching critical levels.
The body’s chronic stress can cause insulin resistance and cause diabetes to become pre-existing. The body needs cortisol and glucose to keep functioning and have the energy to move. When people start to suffer from chronic stress and diabetes, it can become challenging to manage; however, making minor changes to the body like finding ways to lower stress, eating healthy foods, and monitoring glucose levels can help the body reset the glucose and cortisol levels to normal. Doing this can relieve many individuals who want to continue their health journey being stress-free.
Adam, Tanja C, et al. “Cortisol Is Negatively Associated with Insulin Sensitivity in Overweight Latino Youth.” The Journal of Clinical Endocrinology and Metabolism, The Endocrine Society, Oct. 2010, www.ncbi.nlm.nih.gov/pmc/articles/PMC3050109/.
De Feo, P, et al. “Contribution of Cortisol to Glucose Counterregulation in Humans.” The American Journal of Physiology, U.S. National Library of Medicine, July 1989, pubmed.ncbi.nlm.nih.gov/2665516/.
Hucklebridge, F H, et al. “The Awakening Cortisol Response and Blood Glucose Levels.” Life Sciences, U.S. National Library of Medicine, 1999, pubmed.ncbi.nlm.nih.gov/10201642/.
Joseph, Joshua J, and Sherita H Golden. “Cortisol Dysregulation: The Bidirectional Link between Stress, Depression, and Type 2 Diabetes Mellitus.” Annals of the New York Academy of Sciences, U.S. National Library of Medicine, Mar. 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5334212/.
Lee, Do Yup, et al. “Technical and Clinical Aspects of Cortisol as a Biochemical Marker of Chronic Stress.” BMB Reports, Korean Society for Biochemistry and Molecular Biology, Apr. 2015, www.ncbi.nlm.nih.gov/pmc/articles/PMC4436856/.
The body is a well-working machine that can endure anything that is thrown in its way. However, when it gets an injury, the body’s natural healing process will ensure that the body can get back to its daily activities. The healing process of an injured muscle varies throughout the body. Depending on how severe the damage is and how long the healing process will take, the body can recover to a mere few days to a few months. One of the most gruelly healing processes that the body has to endure is a ruptured calcaneal tendon.
The Calcaneal Tendon
The calcaneal tendon or the Achilles tendon is a thick tendon that is located in the back of the leg. This muscle-tendon is what makes the body move while walking, running, or even jumping. Not only that, the calcaneal tendon is the strongest tendon in the body, and it connects the gastrocnemius and soleus muscles at the heel bone. When the calcaneal tendon is ruptured, the healing process can last from weeks to months until it is fully healed.
The Healing Effects of Low Laser Therapy
One of the ways that can help the damaged calcaneal tendons’ healing process is low laser therapy. Studies have shown that low laser therapy can speed up the damaged tendon repair after a partial lesion. Not only that but the combination of ultrasound and low laser therapy has been studied to be the physical agents for treating tendon injuries. The studies showed that the combination of low laser therapy and ultrasound has beneficial properties during the recovery process of treating calcaneal tendon injuries.
The study found that when patients are being treated for their calcaneal tendons, their hydroxyproline levels around the treated area are significantly increased with ultrasound and low laser therapy. The body’s natural biochemical and biomechanical structures on the injured tendon increase, thus affecting the healing process. Another study has shown that low laser therapy can help reduce fibrosis and prevent oxidative stress in the traumatized calcaneal tendon. The study even showed that after the calcaneal tendon is traumatized, inflammation, angiogenesis, vasodilation, and the extracellular matrix are formed in the affected area. So when patients are being treated with low laser therapy for about fourteen to twenty-one days, their histological abnormalities are alleviated, reducing collagen concentration and fibrosis; preventing oxidative stress from increasing in the body.
Overall, it is said that the effects of low laser therapy can help speed up the healing process of repairing the calcaneal tendon. The promising results have been proven since low laser therapy can help repair the damaged tendon, reducing oxidative stress and preventing fibrosis from escalating, causing more problems on the injured tendon. And with the combination of ultrasound, the calcaneal tendon can recover faster so the body can continue its everyday activities without any prolonged injuries.
Demir, Huseyin, et al. “Comparison of the Effects of Laser, Ultrasound, and Combined Laser + Ultrasound Treatments in Experimental Tendon Healing.” Lasers in Surgery and Medicine, U.S. National Library of Medicine, 2004, pubmed.ncbi.nlm.nih.gov/15278933/.
Fillipin, Lidiane Isabel, et al. “Low-Level Laser Therapy (LLLT) Prevents Oxidative Stress and Reduces Fibrosis in Rat Traumatized Achilles Tendon.” Lasers in Surgery and Medicine, U.S. National Library of Medicine, Oct. 2005, pubmed.ncbi.nlm.nih.gov/16196040/.
Wood, Viviane T, et al. “Collagen Changes and Realignment Induced by Low-Level Laser Therapy and Low-Intensity Ultrasound in the Calcaneal Tendon.” Lasers in Surgery and Medicine, U.S. National Library of Medicine, 2010, pubmed.ncbi.nlm.nih.gov/20662033/.
Waking up tired even after getting six or more hours of sleep?
Under a high amount of stress?
If you are experiencing any of these situations, then it might be due to your melatonin and cortisol levels affecting your body and circadian rhythm.
Across the world, millions of people have trouble sleeping. In the United States, there are roughly about 50-70 million people who have a poor quality of sleep. When a person has slept for less than eight hours, they become tired, and many problems can come to them, especially if their lives are hectic. With a hectic lifestyle and poor sleep, it can cause the body to have low energy to get any task done, the cortisol stress hormone will be raised, and diseases like high blood pressure and diabetes can cause problems that can be chronic if it is not treated.
In functional endocrinology, melatonin and cortisol are hormones that the body produces naturally. The cortisol hormone or the stress hormone helps the body be in a state of “fight or flight” mode, which can be a good thing for anyone who is doing a project or going for a job interview. Although when cortisol hormone levels are high, it can lead the body to have complications like inflammation, chronic oxidative stress, and high blood pressure.
The Melatonin Circadian Rhythm
With the melatonin hormone, this hormone tells the body when it is time to sleep. Sometimes though, people do have a hard time sleeping, and taking melatonin supplements can actually relax the body and thus making the person fall asleep. Since the pineal gland produces melatonin from the brain, it can also be found in the eyes, the bone marrow, and the gut to relax the body and making the person fall asleep naturally. Some studies show that the circadian rhythm of the pineal gland that is producing melatonin. By doing this, the research shows that the administration of melatonin can:
One: induce sleep on individuals who have trouble falling asleep.
Two: inhibits the body to wake up naturally from the circadian pacemaker.
Three: shift the circadian biological clocks to increase sleep intake when a person is trying to sleep at an earlier time to get the full eight-hour benefits of sleep.
When a person is working at a 9 to 5 job, they are rising with their bodies and relaxing their bodies after a hard day at work. Studies found out that the melatonin and cortisol hormones help regulate the 24-hour pattern of the body’s function and responses tremendously. With the body’s hormone production cycle, it can be disturbed if the person is staying awake late at night or sleeping during the day. When this happens, the person can get disruptive disorders like mood swings, dizziness, be irritable and depressed, and have metabolic disorders. Not only that, but the body’s immune system and its endocrine system can also be damaged as well, causing the body to be a host to infections and diseases.
There have been more studies on the circadian rhythms in the body, as the studies show how people who work in the night shift have been associated with a vast number of adverse health problems that attack the cardiovascular and gastrointestinal system as well as disturbing the metabolic system. Anyone who has worked the night shift has to change their sleep schedule and adapt to the rapid reorientation in their sleep/wake schedule to go to work and do their job. Since everyone is working at a shift schedule, it can be stressful and can affect a worker’s body performance as well as affecting melatonin and cortisol secretion.
Ways To Support Cortisol and Melatonin
Surprisingly though, there are ways to lower cortisol levels and make sure that melatonin levels are working correctly for the body to function. For cortisol levels to be lowered, a person should do meditative practices, find an enjoyable hobby, and, most importantly, try deep breathing exercises to relax the body from unwanted stress. With deep breathing exercises, it can help the body to release any tension that a person is holding, and the muscles in the body began to relax, and the blood starts to flow. With the melatonin levels, they work together with the body’s circadian rhythm and make sure the body knows when it is time to wake up, sleep and eat. The melatonin hormone can also help regulate the body’s temperature, blood pressure, and hormone levels to make sure it is functioning correctly. When there are high levels of these systems, it can cause the body to develop chronic illnesses and harm the body in the process.
Research shows that melatonin hormones can bind to neurological receptors in the body, thus promoting relaxation. Since melatonin binds to neurological receptors, it can also reduce nerve activity and dopamine levels to make the eyes heavy, thus making the person fall asleep.
With the body being able to naturally produce melatonin and cortisol levels to make sure that the body does not get overly stressed throughout the entire day. Since melatonin is partnered with the body’s circadian rhythm, the body knows when to stay up and fall asleep. Since everyone has a hectic schedule, it is essential to take time and relax and get on a healthy sleep schedule so the body can be healthy and functioning. Some products are here to make sure that the endocrine system is functioning properly and supporting the adrenal glands and sugar metabolism.
The scope of our information is limited to chiropractic, musculoskeletal, and nervous health issues or functional medicine articles, topics, and discussions. We use functional health protocols to treat injuries or disorders of the musculoskeletal system. Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We also make copies of supporting research studies available to the board and or the public upon request. To further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900.
Cajochen, C, et al. �Role of Melatonin in the Regulation of Human Circadian Rhythms and Sleep.� Journal of Neuroendocrinology, U.S. National Library of Medicine, Apr. 2003, www.ncbi.nlm.nih.gov/pubmed/12622846.
James, Francine O, et al. �Circadian Rhythms of Melatonin, Cortisol, and Clock Gene Expression during Simulated Night Shift Work.� Sleep, Associated Professional Sleep Societies, LLC, Nov. 2007, www.ncbi.nlm.nih.gov/pmc/articles/PMC2082093/.
Monteleone, P, et al. �Temporal Relationship between Melatonin and Cortisol Responses to Nighttime Physical Stress in Humans.� Psychoneuroendocrinology, U.S. National Library of Medicine, 1992, www.ncbi.nlm.nih.gov/pubmed/1609019.
Raman, Ryan. �How Melatonin Can Help You Sleep and Feel Better.� Healthline, Healthline Media, 3 Sept. 2017, www.healthline.com/nutrition/melatonin-and-sleep.
Zamanian, Zahra, et al. �Outline of Changes in Cortisol and Melatonin Circadian Rhythms in the Security Guards of Shiraz University of Medical Sciences.� International Journal of Preventive Medicine, Medknow Publications & Media Pvt Ltd, July 2013, www.ncbi.nlm.nih.gov/pmc/articles/PMC3775223/.
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