METABOLIC ENDOTOXEMIA

Metabolic endotoxemia is a condition that affects many people in America. In fact, recent studies estimate that over one-third of adults in the United States have this health issue. It’s been estimated that it may soon be indirectly a leading cause of death. Follow us on this week’s blog to learn what it is and how to prevent metabolic endotoxemia.

Metabolic Endotoxemia

Metabolic endotoxemia is the presence of too much LPS (lipopolysaccharides) in the blood. LPS are toxins that reside on the outer membrane of bacteria that would otherwise not be allowed into our bloodstream. The American Diabetes Association identified bacterial lipopolysaccharide (LPS) as the inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes.  LPS triggers a cascade of immune responses. For example, after binding to its receptor TLR4 (TLR4 is a receptor found on the surface of cells that can detect LPS) or CD 14, there is an elevated level of tumor necrosis factor-alpha (TNFα). TNFα is a protein signaling molecule that is an inflammatory mediator that triggers the innate immune response. The innate immune system, as its name implies, is a primitive type of immunity that all living organisms have. In contrast to the adaptive immune system (which is found in humans and other higher-order species), there are no actual distinguishing features between cells belonging to the innate system or adaptive immune system – they simply look different. TNFα activates more TLR4 which results in more TNFα. As you can see, it becomes a vicious cycle leading to chronic inflammation.

LPS also induces cytokine production by activating inflammatory transcription factors known as nuclear factor kappa B (NF-κB). NF-κB is a protein complex that controls the expression of genes involved in immunity and inflammation. Inducing cytokine production helps our bodies fight off infections. However, it also activates the immune response to clear away cells that are injured or damaged by short-term inflammation. If this clearing of dead cells occurs chronically, it can lead to tissue damage and autoimmune diseases where the body starts attacking its own healthy tissues.

DIET & METABOLIC ENDOTOXEMIA

Paracelsus, a Renaissance physician said: “All things are poison; everything is poisonous; there is nothing without poisonous qualities. Only the dose permits something not to be poisonous.” 

The severity of this disorder depends on how much LPS enters circulation and how sensitive an individual’s body is to these inflammatory agents. As expected, diet and lifestyle are critical when it comes to metabolic endotoxemia and other diseases. 

Inflammatory transcription factors are also activated in response to a high-fat diet rich in saturated fats and low in fruits and vegetables. Inflammatory transcription factors are transcription factors that contribute to the initiation, regulation, and mediation of inflammation.

Saturated fatty acids trigger macrophages to create a cascade of inflammatory signals. Saturated fats refer to a type of dietary fat with no double bonds between the carbon atoms. They are typically solid at room temperature and found in foods such as beef, pork, poultry, butterfat (in dairy products), palm kernel oil, lard (in meat products), and cocoa butter. Inflammatory foods have been linked to causing an inflammatory immune response that results in endotoxemia, which is the presence of bacterial endotoxin (LPS) in the bloodstream.

METABOLIC ENDOTOXEMIA AND DISEASE

The relationship between metabolic endotoxemia and the onset of diabetes, obesity, and heart disease is well established. Metabolic endotoxemia causes the body to have increased cortisol levels. This causes increased insulin resistance, which can contribute to type 2 diabetes. Metabolic endotoxemia causes the body to have increased cortisol levels. This causes increased insulin resistance, which can contribute to type 2 diabetes. In a healthy body, insulin resistance may be caused by high cortisol levels in response to stress. This insulin resistance is typically temporary as a protective mechanism for the body, but in most people who are insulin resistant, a high carbohydrate diet makes them even more insulin resistant. So, these individuals will typically crave carbohydrates when their blood sugar is low from the stress cortisol is causing on their bodies with elevated insulin resistance.

Metabolic endotoxemia causes an increase in persistent free radicals, which contributes to chronic inflammation and aging of the cells. An increase in persistent free radicals is not optimal as this can result in the accelerated development of chronic disease. Chronic inflammation is cause for concern because it is associated with elevated risks of cardiovascular disease, Alzheimer’s disease, cancer, and many other chronic diseases. Metabolic endotoxemia also causes oxidative stress. Oxidative stress refers to the process whereby free radicals in cells cause damage to molecules leading to tissue and organ dysfunction. The human body has both antioxidant and anti-inflammatory mechanisms in place that operate in a feedback loop, such as red blood cells, white blood cells, vitamins C and E, uric acid, nitric oxide synthase (NOS), and more. This feedback loop works by protecting the cells from oxidative damage and removing damaged cells. However, there are many variables that can break the loop using mechanisms called hormesis. Hormesis refers to acute stress that leads to a beneficial effect. For example, exercise causes the body to emit oxidizing free radicals because it requires large amounts of ATP (energy) for muscle contraction. Metabolic endotoxemia however is not a beneficial mechanism. It is the result of an overload of free fatty acids (FFAs), cytokines, and NOS-derived NO which cause circulating endotoxins to disrupt the host’s metabolism. 

Additionally, oxidative stress decreases cellular DNA repair. Cellular DNA repair is critical to our overall health and well-being. As we have discussed in recent blogs, DNA repair is critical for maintaining metabolic homeostasis. Failure to maintain metabolic homeostasis due to DNA damage from oxidative stress can lead to obesity, insulin resistance, and even type 2 diabetes.

In addition to causing insulin resistance and oxidative stress, metabolic endotoxemia has been linked to dysfunction of the hypothalamic-pituitary-adrenal axis. Our HPA Axis is critical for maintaining metabolic homeostasis. Our HPA Axis is responsible for the release of cortisol, our main stress hormone. We often think of the HPA Axis as being involved in stress but it involves every organ system in the body and is critical for maintaining normal body functions, including inflammation. Recent studies have established that in vivo administration of bacterial lipopolysaccharide (LPS) enhances hypothalamic-pituitary-adrenal (HPA) axis function by a mechanism involving endotoxin-stimulated cytokine release.  

IMPORTANCE OF DECREASING INFLAMMATORY ALLOSTATIC LOAD

Deceasing our allostatic load is a component of reaching our optimal health.  Allostatic load refers to the wear and tear on the body through stress. Metabolic endotoxemia contributes to the reduction in our allostatic load. Meeting one’s optimal health includes having a healthy weight, healthy blood sugar levels, and low inflammation among many things. The decreasing allostatic load can be done by increasing physical activity and mindfulness, improving nutrition, reducing stress, maintaining social connections, and getting enough sleep. Decreasing the number of factors involved in the allostatic load will help decrease the overall inflammatory response. 

Don’t know where to start? At the Institute for Human Optimization, we will work with you directly to optimize your well-being. No two patients are the same, so we work with you and create a personalized and individual approach to your health concerns. Contact us today to get started.

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References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695328/

https://diabetes.diabetesjournals.org/content/56/7/1761

https://pubmed.ncbi.nlm.nih.gov/14965237/

https://pubmed.ncbi.nlm.nih.gov/8892362/

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Hashimotos: The Most Common Cause of Hypothyroidism

Hashimoto’s, also known as Hashimoto’s Thyroiditis, is considered to be the most common cause of hypothyroidism. It is an autoimmune disorder that causes your thyroid to produce less than optimal amounts of hormones. The body needs these hormones to regulate its metabolism and other functions. Follow us along as we discuss what Hashimoto’s is and how it relates back to Hypothyroidism.

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Thyroid

The thyroid is a small gland in the front of your neck. It releases hormones that affect everything in the body, from heart rate to energy levels. Hormones produced in the thyroid include T3 and T4, two of the most important thyroid hormones. These hormones are responsible for growth, development, metabolism (the rate at which all chemical processes in the body take place) and many other functions throughout your body.

T3 specifically helps with the thermal regulation of the body and is essential for growth, development, and general homeostasis (stable state).

The thyroid gland produces T4 and then converts it into T3; this conversion process can be inhibited by inflammation. When your body is inflamed (for example, due to injury or illness), your thyroid may not produce enough T3. 

When your thyroid is not working optimally, this can result in an overactive thyroid gland (hyperthyroidism) or an underactive thyroid gland (hypothyroidism).

Thyroid hormones are responsible for many functions throughout the body, including regulating metabolism. It is not rare to see low levels of thyroid and rapid weight gain in the same individual.  Let’s discuss common types of thyroid disorders. 

Hyperthyroidism

Hyperthyroidism is when you have an overactive thyroid gland that generates too much thyroid hormone. This results in symptoms such as:

· Fast heart rate

· Increased appetite

· Excessive perspiration

· Weight loss

· Nervousness, irritability, and/or anxiety

· Diarrhea

· Sensitivity to heat

· And more!

Hypothyroidism

Hypothyroidism is when you have an underactive thyroid gland that does not generate enough thyroid hormone. This results in symptoms such as:

· Fatigue and excessive sleepiness

· Weight gain or inability to lose weight

· Depression, mood swings, and/or irritability

· Muscle pain and stiffness

· Cold intolerance

· Constipation and dry skin

· And more!

Primary, Secondary, Tertiary, and Subclinical Hypothyroidism

There are different types of hypothyroidism. 

  • Primary Hypothyroidism: is when the thyroid gland itself does not maintain adequate levels of T3 or T4. This can be caused by a number of things, but the most common cause in the US is Hashimoto’s Disease. In primary hypothyroidism the problem is with the thyroid itself.
  • Secondary Hypothyroidism: is when the pituitary fails to produce enough Thyroid-Stimulating Hormone (TSH) in response to low levels of thyroid hormone in the blood. This can be caused by pituitary disease, hypothalamic disease, medications that reduce TSH (such as amiodarone or lithium), autoimmune destruction of the pituitary, and more. In secondary hypothyroidism, the issue is not with the thyroid but the  pituitary, which monitors the thyroid.
  • Tertiary Hypothyroidism: is when the hypothalamus fails to produce enough thyrothropin-releasing hormone (TRH).  TRH is needed to stimulate the pituitary to produce enough TSH. TSH is necessary to stimulate the thyroid gland. Research shows that this can be caused by hypothalamic disease, medications that reduce TRH (such as lithium), autoimmune destruction of the hypothalamus, and more.
  • Subclinical hypothyroidism: is an early, mild form of hypothyroidism. Usually, your thyroid is functioning properly but your TSH levels are slightly elevated. This form of hypothyroidism is most common in women, the elderly, and those with other autoimmune diseases.

Hashimoto’s 

The most common cause of hypothyroidism is Hashimoto’s.  It’s important to note that Hashimoto’s and hypothyroidism are not the same conditions. People who have Hashimoto’s often progress to hypothyroidism, or an underactive thyroid.  But not always. Sometimes people can be diagnosed with both at the same time, while some might only ever experience Hashimoto’s and never develop hypothyroidism. Hashimoto’s is an autoimmune disorder. Autoimmune disorders are when your body’s immune system starts attacking healthy cells. In the case of Hashimoto’s, this is when you have an immune system that incorrectly identifies the thyroid gland as something foreign and attacks it, resulting in damage to your thyroid. 

Although Hashimoto’s most often results in hypothyroidism, it can also cause hyperthyroidism, when your thyroid gland is overactive. However, this form of hyperthyroidism may go undetected because some of the symptoms are similar to that of people with Hashimoto’s who present with hypothyroidism (such as weight gain, fatigue, lethargy, lack of concentration).  

What are the symptoms of Hashimoto’s? 

Hashimoto’s is usually asymptomatic for years which makes it difficult to diagnose. One of the first signs of this disease would manifest through fatigue, which is the most common symptom. Other symptoms include weight gain, feeling cold all the time, constipation, and depression.  

With Hashimoto’s, symptoms will worsen as your disease progresses and it becomes harder to recover from them. 

People with Hashimoto’s typically present with:

· A goiter (an enlarged thyroid)

· Decreased TSH levels

Hashimoto’s is caused by antibodies attacking the thyroid, which causes it to not produce enough hormones. The specific triggers for this attack are unknown but there are some ideas on why this happens. Some research links Hashimoto’s to genetics, exposure to viruses and environmental toxins, chronic inflammation, gut health issues, diets high in goitrogens, obesity, soy, and bacterial or viral infections. There is also a belief that Hashimoto’s may be brought on by stress hormones.

Hashimoto’s is important to address because left untreated, it can lead to an underactive thyroid or hypothyroidism. The thyroid gland is responsible for producing thyroxine which is responsible for regulating your metabolism. It also affects the way you use energy, the way your body uses food for energy, how your body molds fat and sugar, as well as how your heartbeats. An underactive thyroid can have long-term health effects such as weight gain, anxiety, lethargy, and depression. 

Personalized Approach to Hashimoto’s

Generally, your health care provider will take your medical history and perform a physical exam. Additionally, they will check your Thyroid Stimulating Hormone (TSH) and your Free T4 (FT4) levels. 

At the Institute for Human Optimization, we believe the best way to help our patients is by having all the insight we can get access to. This in turn helps us create a personalized, precise, protocol unique to you. 

Some blood tests we will look at include but are not limited to:

  • Checking levels of Thyroid peroxidase Ab, Thyroglobulin Ab, and TPO-ab. These are antibodies that are fighting against your thyroid gland.  
  • Total T4 will be reviewed to look into the levels of protein that the thyroid gland produces. 
  • Total T3:   the active form of thyroid hormone 
  • Free T3: the active form of thyroid hormone 
  • Reverse T3: Reverse T3 is a protein that binds to T3. When this happens it makes T3 not available for the body to use, which will make your thyroid gland slow down production of thyroid hormone.
  • Thyroid Binding Globulin: Thyroid Binding Globulin will be tested to look for levels of protein that your thyroid gland produces.  
  • Thyroglobulin Antibodies: the presence of this antibody is a marker for Hashimoto’s disease.

People with Hashimoto’s, or autoimmune hypothyroidism, have special needs when it comes to thyroid hormone replacement therapy.  It can be difficult to find the right type of medication for you – what might work well in one person may not work at all in another patient. 


Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

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Heart Rate Variability

Heart rate variability is a new technique in the field of biofeedback that can help provide a more accurate picture of your physical and emotional state. This blog post will explore what heart rate variability is, how it works, and some benefits you may see from using this new way to track well-being. 

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Heart Rate Variability (HRV) is thought to be originally discovered by K. Grinberg back in 1896 but was not researched until the 1960s. Heart rate variability is a measurement of the time between heartbeats. It can be measured in milliseconds, which are 1/1,000th of a second. HRV is measured by your heart’s response to breathing patterns. As you breathe in, your body absorbs oxygen and nutrients that allow the lungs to release carbon dioxide when you exhale. As the body absorbs oxygen, it sends an electrical signal to the heart muscles to contract. This contraction is what pushes blood throughout your body via the circulatory system. During exhalation, there is less pressure on your heart since no new air comes in with each breath (and you exhale carbon dioxide). A low HRV value means that it takes longer for the heart to relax and fill with blood between beats, causing reduced circulation throughout the body. 

HRV AND SLEEP

Sleep is critical to our overall health.  Not only does our body use this time to repair itself, but it is also an opportunity for the brain to go through stages of mental development. The average adult sleeps 7-8 hours per night. However, not all sleep is created equal. There are 4 stages of sleep and two types of sleep: rapid eye movement (REM) sleep and non-REM sleep (which has three different stages). 

Stage 1: is non-REM sleep. It is described as light sleep and you can be lightly stimulated without waking up. Additionally, your brain waves begin to slow down compared to your daytime activity. 

Stage 2: This stage is a deeper non-REM sleep. It is more difficult to be woken up during this phase, your brain waves further slow down and your body temperature begins to drop.

Stages 3: In these final stages of non-REM sleep, there are very slow brain waves called delta waves.  

Stage 4: REM Sleep. Rem sleep is when your eyes move rapidly back and forth behind your closed eyelids, where you are in a deep sleep but dreaming.

RV is very important when it comes to sleep. In fact, HRV has been successfully used to screen people for possible referral to a Sleep Lab. Typically, an individual’s heart rate will vary the most while awake and then decrease at night during REM sleep.  In non-REM sleep, HRV will begin to decline as your heart rate slows down. In REM sleep, however, HRV begins to pick back up again because it is a very active time for the body and you have a faster heart rate. 

Research has shown that an individual with a low HRV value may have a hard time transitioning from being awake to entering deep REM sleep because their nervous system won’t be able to relax between breaths. This may be one reason why those with a low HRV might have difficulty sleeping or even feel tired during the day. An individual with a high HRV will most likely have an easier time transitioning from wakefulness to sleep, and will also maintain their deep REM sleep throughout the night.

WHY IS HRV IMPORTANT

HRV is important in medicine today. HRV analysis is a recognized tool for the estimation of cardiac autonomic modulations.  Cardiac autonomic modulations refer to the changes of cardiac parasympathetic and sympathetic activity in response to variations in respiratory rates. Heart Rate Variability is the variability within your heart rate over time, which is also measured by taking an ECG recording.  It’s widely used nowadays for tracking health and is even a feature on common smartwatches. HRV has been used to predict mortality after a heart attack, among other things. 

HRV is used as a marker for physical and mental stress. How so? The parasympathetic nervous system lowers heart rate and controls the “rest and digest” function. The sympathetic nervous system raises the heart rate, dilates blood vessels to generate a fight or flight response which is particularly useful when dealing with stressful events. As HRV increases, your cardiac output decreases as you enter a state of parasympathetic dominance. For example, those with depression or Post Traumatic Stress Disorder have been found to have a lower HRV. Low HRV may indicate that the individual has a harder time recovering from daily stressors, which could ultimately lead to health issues if left untreated.

HRV may be able to give some insight into how stress has been affecting your mental and physical health. If an individual is having a hard time maintaining good cognitive function, HRV can be used as a gauge to determine whether that person needs more rest or if they need to take time off from work. In the case of those who have anxiety or depression, low HRV may be able to predict the likelihood of an individual experiencing issues with their mental health.

Generally, a low HRV is linked with an increased risk of death and cardiovascular disease. By taking HRV to heart, individuals are able to get a better picture of their health. There are also times when high HRV may indicate that the person’s body is not operating at its best. An example of this would be an individual who does workouts that are too intense for them to handle. 

INCREASING YOUR HRV

When a person is in a stressful situation, their sympathetic nervous system takes over and an increased amount of cortisol will be released. This leads to a lower HRV which signals the body that there is stress present.

In response, one can attempt to reverse this effect by breathing slowly and deeply while engaging in relaxation techniques such as meditation or yoga. People who have a high HRV have been shown to have higher levels of a neurotransmitter called GABA, which is naturally released when a person is present in a relaxed environment.

Increasing your HRV will also increase the amount of energy that your body uses as it requires less energy from cortisol and adrenaline for this process. This leads to better blood pressure, weight management, performance under stress, and other optimal outcomes.

Just like you may use smart technology to count your steps, tracking HRV may be a useful tool to motivate behavioral and lifestyle change. For example, Sleep HRV measurements can provide insight on how you rate compared to other users in similar age groups. While HRV biometric tracking is still a new concept, I am hopeful it will help patients be more participatory in their health journey. 

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225923/

https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Understanding-Sleep

https://pubmed.ncbi.nlm.nih.gov/21658979/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680518/

https://pubmed.ncbi.nlm.nih.gov/27918706/

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