Explainer (long version)

Retinoids and Their Impact on Sensory Receptors

Retinoids, commonly known for their applications in skincare and medical treatments, have a significant biological role that affects our sensory system. They activate two important sensory receptors: TRPV1 and TRPA1. While this activation is essential for normal functioning, it can also lead to chronic stress, potentially contributing to various diseases and neurological disorders.

Many people are unaware that retinoids are added to our food supply in small doses that we consume daily. This can lead to the chronic activation of sensory receptors, causing unnecessary stress responses in our bodies.

Understanding Retinoids and Sensory Receptors

Retinoids are a group of chemical compounds derived from vitamin A, which are crucial for a variety of biological processes, including vision, cell growth, and immune function. Their ability to activate sensory receptors—specifically TRPV1 and TRPA1—offers insights into how our bodies perceive and process external stimuli. TRPV1 and TRPA1 are part of the Transient Receptor Potential (TRP) channel family, which is known for its role in detecting and responding to temperature and chemical stimuli.

These channels significantly influence how our bodies perceive and react to the environment. TRPV1 is primarily associated with sensations of pain and heat, while TRPA1 responds to environmental irritants and plays a role in inflammatory responses. Together, they have profound effects on pain signaling and neurological processing. Let’s explore their physiological roles and their connection to the nervous system.

Physiological Roles of TRPV1 and TRPA1

TRPV1 and TRPA1 are sensor proteins located in the membranes of certain cells, including nerve fibers. They detect and respond to various environmental factors, such as temperature changes, chemical irritants, and tissue damage.

TRPV1 is often referred to as the "capsaicin receptor" because it responds to capsaicin, the active component in chili peppers. It activates in response to heat or chemical signals and plays a central role in pain perception.

Conversely, TRPA1 reacts to environmental irritants like mustard oil, air pollutants, and cold temperatures, earning it the nickname "irritant receptor."

When activated, these channels allow calcium and sodium ions to flow into the cells, initiating pain signals. This mechanism is essential for detecting harmful stimuli and triggering protective responses. However, when TRPV1 and TRPA1 are continually activated, they can lead to maladaptive changes, increasing sensitivity and prolonging pain.

The Mechanism of Retinoid Activation

The versatility of the TRPV1 receptor is primarily attributed to the vanilloid-binding pocket, a crucial site where molecules such as retinoids can attach. When retinoids bind to this receptor, they interact with specific residues in the vanilloid-binding domain, effectively "unlocking" the channel. This process allows calcium and sodium ions to flow into the cell, which is essential for transmitting sensory signals.

Retinoids not only stimulate the receptors but also trigger a sensory response that can lead to pain and irritation. However, the activation of TRPV1 does more than just induce discomfort; it initiates a complex response within the body. When activated, TRPV1 triggers the sympathetic nervous system—often referred to as the "fight or flight" response. This leads to the production of a stress response and the release of neuropeptides like Substance P and Calcitonin Gene-Related Peptide (CGRP).

These neuropeptides act like biochemical alarms, prompting the release of histamine and cytokines, which promote inflammation as part of the healing process. Over time, with repeated or chronic activation, this inflammation can transition from being a necessary response for healing to becoming a problem in itself, leading to disorders of chronic inflammation.

Role of TRPV1 and TRPA1 in the Stress Response

When TRPV1 and TRPA1 are over-activated, they can increase the sensitivity to stress, leading to heightened responses even to mild stressors. This hyperactivation can tip the scales, resulting in chronic stress. Such continuous activation stresses the body's resources, like constantly revving a car engine. It might be efficient in the short term, yet it significantly wears out the engine in the long run.

In summary, long-term activation of TRPV1 and TRPA1 creates a stress cycle. Your body thinks it's always in danger and struggles to calm down.

The use of retinoids, whether topical or in food, supplements, and medications, activates the TRPV1 and TRPA1 sensory receptors, which induce the sympathetic nervous system's fight-or-flight stress response. Continual usage or ingestion of retinoids on a regular basis will overstimulate the sensory receptors, leading to the negative stress that causes disease and disorders.

Chronic Stress and Its Consequences

Connection to Oxidative Stress

Chronic stress isn't just a feeling of being overwhelmed; it leads to biological wear and tear in the body. One significant consequence of chronic stress is oxidative stress, which occurs when there is an imbalance between free radicals and antioxidants. This imbalance can result in cellular damage and accelerate the aging process. Recent studies show that excessive use and ingestion of retinoids can further accelerate aging by inducing stress and increasing reactive oxygen species (ROS), which directly heighten oxidative stress.

Oxidative stress occurs when free radicals outnumber antioxidants in the body, leading to cell damage over time. This imbalance can trigger or worsen various diseases. For a comprehensive overview, see our list of 40 common health issues associated with oxidative stress.

Now, let’s consider another important factor in our food supply: the use of gibberellic acid in the production of grains, fruits, and vegetables. Gibberellic acid can lower the antioxidant levels in the foods we consume, reducing their ability to counteract the reactive oxygen species that contribute to oxidative stress-related diseases. Learn more about Gibberellic Acid in posts in this blog post.

The Effects of Stress on Our Metabolism

Stress impacts your body in ways you might not expect. When you are under pressure, your body releases a hormone called cortisol, which acts like an alarm system. While this is beneficial in small doses, it can lead to problems if it remains activated for too long.

So, what does cortisol do? One of its key roles is to regulate how your body uses energy.

During times of stress, cortisol changes how your body processes molecules like purines—essential building blocks for DNA and energy. When cortisol levels stay elevated over time, purine levels can rise, putting additional strain on your body.

Imagine your body is in a constant state of alert; this is what chronic stress feels like. In this survival mode, your body alters its energy usage in several ways:

1. Sugar Metabolism Takes a Hit: Under stress, your body conserves sugar for emergencies rather than using it for energy. As a result, your cells struggle to utilize glucose effectively, leading to high blood sugar levels.

2. Fat Burning Slows Down: Typically, your body uses fat for energy, but stress causes it to seek quicker energy sources. Consequently, fat burning takes a backseat, which is not ideal for your overall health.

3. Increased Protein Requirements and Muscle Breakdown for Fuel: When under stress, your need for protein increases. If you do not consume enough protein in your daily diet, your body will start using muscle protein for energy. This is similar to using furniture for firewood; it may work, but it’s not sustainable.

   
   

Over time, these changes can lead to various health issues, including elevated blood sugar, fat accumulation, and muscle loss. This is why many people feel the need to engage in regular exercise to lose weight and maintain or build muscle. Managing stress is, therefore, crucial for keeping your body functioning smoothly.

When the body relies on protein for energy during stressful times, more purines are produced. Since protein contains a high amount of purines, they are broken down into uric acid. When stress persists, the body increases protein breakdown, raising the demand for protein in your diet. Problems can arise when purines accumulate or are not eliminated quickly enough, this can raise uric acid levels and can lead to issues like gout and kidney stones as the body struggles to remove excess uric acid.

Now, let’s add in our third concern. The excessive use of proteolytic enzymes in food production. Chemical enzymes are strong catalysts used to quickly and efficiently break down proteins. When we consume these enzymes, we break down proteins quickly, producing excess purines and uric acid. Uric acid can build up to form urate crystals and stones that can damage the kidneys as they work to excrete liquid waste.

Bones, Teeth and Calcium Crystals

As mentioned above the stress response releases neuropeptides like Substance P and CGRP (Calcitonin Gene-Related Peptide).

Substance P plays a crucial role in maintaining the health and strength of your bones and teeth by regulating two types of cells: osteoblasts, which build bone, and osteoclasts, which break down bone. When Substance P is released from nerve endings, it signals certain cells called synovial fibroblastic cells to produce more RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand) and less OPG (Osteoprotegerin).

RANKL acts as a "go" signal for osteoclasts, making them more active and prompting them to break down more bone. In contrast, OPG functions as a "stop" signal, preventing excessive bone breakdown. When Substance P increases RANKL levels and decreases OPG levels, it creates an imbalance that favors more break down. When bone and teeth are broken down, their mineralized matrix releases calcium into circulation. This occurs because osteoclasts degrade the hydroxyapatite structure (the primary mineral in bone and teeth) to free calcium ions.

 While this process releases calcium, which is necessary for transmitting sensory signals, excessive calcium in the bloodstream, especially under chronic stress or metabolic changes, can result in the precipitation of calcium salts. These salts form calcium crystals, particularly in areas like joints, kidneys, or other tissues where supersaturation occurs.

To protect the skeletal structure from continuous activation and excessive bone loss, the body alters its metabolism to increase fat storage. Adipose tissue (fat cells) also releases OPG, helping to mitigate excessive bone loss. This phenomenon is similar to how babies or children gain weight just before a growth spurt; their bodies store both energy for growth and fat cells that express OPG, thus promoting the activity of osteoblasts to form strong bones.

Numerous studies have shown that retinoids increase bone resorption by elevating the RANKL/OPG ratio.

Stress and Addiction

TRPV1 and TRPA1 are like sensors in your body. They detect things like heat, pain, or irritation. These sensors get activated with changes in temperature, retinoid use, when you eat spicy food, breathe in smoke, or feel pain. That’s their normal function.

However, when these receptors remain chronically active, they can impact your brain's functioning. They continuously send signals to areas responsible for pleasure, learning, and craving, leading your brain to crave things that trigger these receptors, even if those things are harmful.

Over time, your brain can become accustomed to the constant signals, resulting in a dependency on these stimuli to feel pleasure. This can lead to addictive behaviors, much like a switch that gets stuck in the "on" position; your body begins to desire more of whatever keeps activating it.

In short, when TRPV1 and TRPA1 are always active, they can push your brain toward habits that turn into addictions. It’s a bit like your body getting tricked into thinking it needs something, even if it’s not good for you.

Think about how many people crave bread, cheese, or spicy foods. Have you noticed how particular fast-food chicken is like a drug to many people? They love it and cannot seem to get enough of it! Look closely at the ingredients of many of the products. They contain skim, non-fat milk and, therefore, vitamin A palmitate, a synthetic retinoid. As we mentioned early on, retinoids activate both TRPA1 and TRPV1 receptors, effectively making the seemingly healthy foods we eat bad for us.

The chronic activation of these receptors increases the size of the amygdala and the number of dopamine receptors, so we unknowingly become dopamine addicts. Anything from social media, video games, distractions, and even excessive eating and exercising to smoking, drinking, and drugs; anything that produces endorphins and releases dopamine will make us feel good and can become addicting.

This is why opioids work so well. Both opioids and natural endorphins bind to the nerve endings where the TRPV1 and TRPA1 receptors are found. They will ease our pain and make us feel good, but they quickly and easily can become addictive.

Squirrel! While it has become funny to shout squirrel when someone is distracted, we need to understand that distractions release dopamine. Each time you are distracted you get a shot of dopamine causing you to feel good. Because of this, you might actually become addicted to distractions and crave the new, shiny objects that stimulate your reward pathway.

We need to break the cycle. 

The simplest way to do this is to eliminate all forms of retinoids from our diets, supplements, and skincare products. After that, we must retrain our autonomic nervous system to rebalance effectively:

1. Consume plenty of fats containing oleic acid in the sn-2 position to calm and heal the receptors.

2. Choose fruits, vegetables, or antioxidant supplements that are not grown with Gibberellic acid.

3. Avoid foods produced with or containing potent industrial enzymes.

4. Stop fearing fruit and carbohydrates, as they provide the energy our bodies and brains need to restore balance and facilitate healing.

5. Practice diaphragmatic breathing, focusing on a longer exhale to release carbon dioxide and improve gas exchange in the lungs.

6. Learn to listen to the signals our bodies send when they sense trouble and take action before pain, structural, or genetic damage occurs.

At Tranquility Foods, we are dedicated to raising awareness about this important information. We encourage you to join us to learn and empower yourself to take control of your physical and mental well-being. Explore our website. Share our work with any one who might be looking for a complimentary perspective and work with us to create improved wellness for ourselves and future generations.