Innovative Health Improvement

Ketosis Can Lower Chronic Inflammation and Improve Metabolic and Mental Health in 6 Ways

β-hydroxybutyrate is a testament to the millions of years of our evolution, transcending mere molecular classification, as it has remarkable effects on the body and mind.

β-hydroxybutyrate is not just another molecule. It’s a potent byproduct of our evolution.

β-hydroxybutyrate (BHB)is critical for our cells, tissues, and organs. Besides reducing inflammation, it can create alternative energy, serve as a signaling molecule, enhance cognitive and neurological function, neutralize free radicals, lower blood glucose levels, and improve insulin sensitivity.

In addition to many remarkable benefits, one of the most noticeable aspects of ketosis is its ability to lower chronic inflammation and produce anti-inflammatory effects in the body as a signaling molecule.

Based on requests from subscribers, the primary purpose of this article is to provide a specific overview of the mechanisms of BHB and its role in reducing chronic inflammation in plain language without going into scientific or technical details. However, I link scientific papers for those interested in exploring the terms.

Chronic inflammation is the root cause of various metabolic and mental health disorders. While BHB serves as an alternative energy source, it also acts as a signaling molecule, remarkably affecting our metabolism, immune system, and endocrine system.

I have been actively practicing ketosis for over three decades and have not experienced any adverse side effects. Instead, I have noticed incredible benefits. I documented my decades of experience in previous articles.

As I provided a step-by-step guide to entering ketosis safely and naturally and guided omnivores, herbivores, and carnivores to enter ketosis effectively, making dietary changes, I will not repeat them in this story.

I specifically wrote about BDNF before because, besides improving my metabolic health, BDNF (empowered by BHB) changed my brain chemistry, enhanced my cognitive performance, and contributed to augmenting my focus, attention, working memory, and procedural memory.

I wrote this article when in deep ketosis. So this story is not just a theoretical piece, even though it reflects critical information from theories in the literature.

My goal is to reflect on my sensible experimentation for decades and confidently present this piece as a testimony to the positive effects of ketosis for healthy people.

Despite some misconceptions, BHB has been a well-studied molecule with solid scientific backing since the 1920s. However, ketosis might not suit everyone and might cause side effects for some people.

For example, those with type I diabetes, some type II diabetes, liver or kidney diseases, eating disorders, and pregnant and breastfeeding women need medical supervision. The riskiest effect of ketosis in underlying conditions is ketoacidosis which mainly happens to type I diabetes.

What is BHB, and why is it such a critical molecule for survival?

β-hydroxybutyrate (BHB) is known as a ketone body. The liver produces this molecule during the ketosis process. Ketosis is a metabolic state. The body burns fat molecules for energy instead of sugar in this state.

This unique molecule has long been known for its many benefits. However, recent studies have uncovered even more valuable properties of this molecule.

BH can play a vital role in the body and mind. For example, it impacts energy production, neurological function, cognitive function, and metabolic alterations like improving insulin sensitivity, lowering blood glucose levels, and reducing inflammation.

BHB can act as a signaling molecule. It interacts with genes, enzymes, and various signaling pathways to regulate the expression of pro-inflammatory molecules and promote anti-inflammatory responses.

These interactions result in a decline in inflammation and oxidative stress, leading to improved physical and mental health.

This molecule can bring multiple benefits for our survival and well-being. However, in this story, I will mainly focus on its importance in managing and defeating chronic inflammation, as it is a root cause of numerous health conditions.

The power of BHB comes from its ability to interact with different genes and enzymes as a signaling and modulating molecule.

BHB can interact with genes, enzymes, and different signaling pathways to modulate the expression of pro-inflammatory molecules and increase the expression of anti-inflammatory molecules, as I explain in the following sections.

These effects of BHB can reduce inflammation and oxidative stress, improving our physical and mental health.

Furthermore, BHB can serve as a cleaner energy source for our cells than glucose, as I explain in the next section.

Here is why BHB is a cleaner source of energy for our cells.

Scientists found that BHB is a cleaner energy source than glucose, producing fewer “reactive oxygen species” (ROS) than glucose metabolism.

In addition, BHB does not cause the formation of “advanced glycation end products” (AGEs).

ROS are molecules that can damage our cells, cause inflammation, and speed up the aging process. AGEs are associated with metabolic disorders such as diabetes.

Here’s how BHB interacts with genes.

Numerous studies indicate the anti-inflammatory effects of BHB in various organs, including the brain.

One of the mechanisms BHB causes these effects is via its interactions with various genes. As I documented previously, oxidative stress can affect us at a genetic level.

BHB can modulate the expression of genes involved in oxidative stress and inflammation. For example, some studies identified that BHB might reduce the expression of pro-inflammatory genes, like TNF-alpha IL-1b and IL-6, in adipose tissue, muscles, and the liver and contribute to insulin sensitivity.

Likewise, BHB might also increase the expression of the anti-inflammatory gene PPAR-gamma in adipose tissue, muscles, and the liver. PPAR-gamma is a transcription factor. It regulates the expression of genes involved in inflammation and glucose metabolism.

In addition, BHB might interact with genes related to the antioxidant defense system. For example, it can activate the transcription factor Nrf2, a master regulator of the antioxidant response element. This process might reduce the ROS levels, neutralize them, and lower oxidative stress.

BHB might also increase the expression of the gene encoding for enzymes like superoxide dismutase and catalase. These enzymes might neutralize reactive oxygen species and prevent oxidative stress.

An Overview of BHB’s 6 Mechanisms for Lowering Chronic Inflammation

1 — BHB can lower blood glucose levels.

I start with this most researched aspect. When the body starts producing ketones, especially BHB, it primarily uses fat as a fuel source instead of glucose. This metabolic shift in energy utilization leads to a decrease in blood glucose levels.

Decades of studies indicate that high blood sugar levels (hyperglycemia) are a known cause of inflammation, triggering the release of pro-inflammatory molecules such as cytokines and chemokines.

These molecules are created as a response to injury and infection. However, when the immune system creates molecules in excess amounts, they lead to chronic inflammation, the root cause of various diseases.

For example, high blood sugar levels can cause inflammation through advanced glycation end product (AGEs) formation. AGEs are formed when glucose molecules bind to proteins and fat molecules in the body. AGEs can lead to structural and functional changes in these molecules and activate the immune system.

Why do AGEs matter? Because they can cause type II diabetes, cardiovascular diseases through atherosclerosis, or Alzheimer’s disease through the formation of amyloid plaques.

The impact of AGEs on the heart is critical because high blood sugar levels can cause damage to the endothelial cells that line the blood vessels, leading to inflammation and the development of atherosclerosis.

Atherosclerosis is one of the root causes of heart disease and stroke. After all, blood vessels become narrowed and hardened, preventing blood flow to tissues.

Moreover, high blood sugar levels can also cause damage to the nerve cells, leading to inflammation of the nervous system. This condition is known as diabetic neuropathy.

2 — BHB can modify immune response favorably.

BHB can suppress the production of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, MCP-1). These molecules activate the immune system and promote inflammation to recover the tissues from injury or overuse.

Cytokines are small proteins involved in cell signaling that can increase or decrease inflammation. Various cells, like white blood cells and fibroblasts, produce them.

In addition to decreasing pro-inflammatory cytokines, BHB can increase the production of anti-inflammatory cytokines (IL-10 and TGF-β). These cytokines can counteract the effects of pro-inflammatory cytokines.

When IL-10 and TGF-β levels increase in the blood, pro-inflammatory markers such as C-reactive protein (CRP) levels decrease.

CRP is the gold standard for me, as my healthcare consultants have measured my inflammation markers for decades as I suffered from chronic inflammation and autoimmune disorders.

3 — BHB can reduce oxidative stress.

Excessive oxidative stress is one of the major causes of chronic inflammation, as I documented in previous articles. Therefore, in every health article, I highlight the importance of stress for our well-being.

In a nutshell, oxidative stress refers to a condition in which the antioxidant defense system is overwhelmed because of free radicals. As a result, these reactive molecules might damage cells. Thus, they might contribute to the progress of chronic diseases.

Food is essential for our survival. However, every bite we add to our stomach has the potential to produce reactive oxygen species during the energy production process and activate the immune system to create inflammation.

How can BHB help with this undesirable situation? First, as signaling molecules, BHB and other ketone bodies can scavenge free radicals and neutralize them. This process can lower the amount of damage caused by these reactive molecules.

But as a hero, BHB does not stop there. It can stimulate the production of antioxidant enzymes such as glutathione peroxidase, superoxide dismutase, and catalase.

The role of these enzymes is to neutralize free radicals and reduce oxidative stress in our cells. By the way, glutathione is the master antioxidant in the body, as I explained in a previous article.

4 — BHB can inhibit signaling pathways producing pro-inflammatory molecules

So far, studies indicate two pathways, the Nuclear Factor Kappa B (NF-KB) and mitogen-activated protein kinase (MAPK), associated with the production of pro-inflammatory molecules that BHB inhibits.

The NF-KB pathway regulates genes involved in inflammation, immunity, and cell survival. When activated, it moves to the nucleus and triggers the expression of genes for pro-inflammatory cytokines, chemokines, and adhesion molecules.

The MAPK pathway comprises three kinases phosphorylate targeting proteins and regulating cellular processes such as gene expression, cell survival, and differentiation.

The NF-KB and MAPK pathways play vital roles in producing pro-inflammatory molecules. Response to pathogens, toxins, oxidative stress, and cellular damage can activate them. Regulating these pathways is valuable for creating therapies or drugs targeting chronic inflammation.

5 — BHB can regulate autophagy and mitophagy.

BHB plays a vital role in regulating autophagy. Autophagy is a cellular process in which damaged, or unnecessary cellular components are degraded and recycled. This process maintains cellular homeostasis.

I introduced them in previous articles because autophagy and mitophagy are comprehensive topics. These processes are critical in lowering stress and inflammation by removing garbage from the body and contributing to longevity.

In terms of BHB’s contribution to autophagy and mitophagy, it can stimulate these processes in various cell types and mitochondria. BHB can activate the critical regulator of autophagy, the AMP-activated protein kinase (AMPK) pathway.

BHB can also impact autophagy by modulating the activity of autophagy-related genes and proteins (P62, Beclin-1, and LC3). This modulation can empower the autophagy process.

Therefore, long-term fasting, which creates substantial ketone bodies, indicates increased autophagy, as I discussed in previous articles based on my experience.

The reason I felt much younger in my 50s than in my 20s is due to the autophagy and mitophagy-producing lifestyle that I transparently shared in previous stories.

6 — BHB can improve gut health.

I left this to the end, as ketosis unknowingly contributed to fixing my leaky gut years ago. I didn’t know the mechanism then, but recent studies shed light on this remarkable benefit of BHB.

The key mechanism is BHB can decrease gut permeability by modulating and preventing pro-inflammatory molecules from entering the bloodstream. Therefore, we must understand this anti-inflammatory feature of BHB to improve our gut health.

When the gut barrier is damaged, it allows pro-inflammatory molecules to enter the bloodstream. This undesirable situation, known as gut permeability (leaky gut), can lead to systemic inflammation and autoimmune disorders.

Some studies indicate that BHB can lower the risks and even contribute to treating inflammatory bowel disease (IBD). This is a condition characterized by chronic inflammation of the gut.

In addition, recent studies also indicate that BHB might increase the diversity of the gut microbiome and improve obesity-related inflammation and insulin resistance.

The Impact of BHB on the Brain, Heart, and Liver.

In this section, I only mention these three organs as an example.

However, BHB can also contribute to the health of other organs, especially the pancreas, kidneys, stomach, gut, and muscles, by improving energy metabolism and lowering oxidative stress and inflammation, lowering the risk of metabolic disorders.

People ask me why I don’t lose muscle and keep abs after my 50s by eating one meal daily. The short answer is BHB protects muscles as an alternative energy source and burns visceral fat instead by making the body more insulin sensitive.

1 — BHB can improve cognitive function and the performance of the brain.

BHB improves cognitive function by providing an alternative energy source for the brain during low glucose availability. The brain is highly dependent on glucose as an energy source.

Creating an alternative energy source puts the brain in a favorable position as a treatment or preventative method, such as increasing cognitive reserves as we age.

When the body lacks sugar or food from carbohydrates or proteins (for any reason) or receptors cannot utilize glucose due to neural damage, such as in neurodegenerative disorders, the brain can happily use BHB as an energy source.

I covered the antioxidant benefits of BHB in previous sections, but I’d like to highlight its importance for cognitive health. By reducing oxidative stress, BHB can protect neurons, increase energy efficiency, and put the brain in growth mode by increasing BDNF (Brain-Derived Neurotrophic Factor), as I explained in a previous article.

BDNF is active in brain regions such as the hippocampus, the cortex, the basal forebrain, and the cerebrum. These regions help us learn and build new memories. For example, practitioners observed low BDNF levels in Alzheimer’s patients.

2 — BHB can improve heart health.

In addition to lowering inflammation to prevent atherosclerosis, BHB can contribute to heart health by lowering blood pressure and cholesterol levels. In addition, it can improve blood flow and lower oxidative stress on the heart.

3 — BHB can improve liver health.

In addition to lowering inflammation, BHB can also contribute to detoxifying the liver. It can also lower liver damage by neutralizing harmful free radicals and lowering oxidative stress.

Summary and Takeaways

β-hydroxybutyrate (BHB) can lower chronic inflammation by interacting with various genes, enzymes, and signaling pathways to inhibit pro-inflammatory and improve anti-inflammatory responses.

I only focussed on inflammation in this article as it is a broad topic covering both physical and mental health.

You might check my experience covering other lifestyle changes contributing to defeating chronic inflammation and rheumatoid arthritis, an autoimmune condition.

BHB research on obesity, type II diabetes, neurodegenerative diseases, cardiovascular diseases, mitochondrial disorders, weight loss (reducing visceral fat), and cancer treatment proliferates.

Besides BHB, the body also creates two other ketone bodies: acetoacetate and acetone. However, it produces them in fewer amounts. The bloodstream will always keep some ketones. Ketone bodies rise as the glucose decreases and ketosis gets intensified.

Therefore, I chose a ketogenic diet (high healthy fats consuming around 200 grams a day) with a time-restricted eating regimen to reap the benefits of deep or mild ketosis for metabolic and mental health.

Ketogenetic diets can speed up entering ketosis and increasing BHB. However, it is also possible to enter ketosis without following a strict keto diet. I summarized a case study in an article titled Here’s How Amy Entered Ketosis without Following a Ketogenic Diet. For example, fast-mimicking diets can help with low levels of ketosis.

So you can initiate ketosis in other ways. From my experience, intermittent fasting is an efficient way. However, long-term fasting is ideal for those who want to stay in deep ketosis, such as having three or more nmol BHB in the bloodstream.

As a last resort, those who cannot do keto diets or fast have the option of supplementing. MCT oil, ketone salts, and ketone esters can be used as supplements. They are publicly available without needing a prescription.

Ketone salts are ketones bonded with mineral ions such as calcium, magnesium, and sodium. Ketone esters are ketones bonded with alcohol and are more potent and effective, but not many people can handle the taste.

Even though ketone salts and esters are publicly available and considered safe, there are no long-term studies documenting the risks of ketone salts. Thus, we need to be careful while supplementing.

Please also be careful with the side effects of MCT oil (hexanoic, octanoic, decanoic, and dodecanoic acids) at higher doses. It can cause stomach upsets and diarrhea.

Thank you for reading my perspectives. I wish you a healthy and happy life.

As a new reader, please check my holistic health and well-being stories reflecting my reviews, observations, and decades of experiments optimizing my hormones and neurotransmitters. I write about health as it matters. I believe health is all about homeostasis.

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