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Adenomyosis Is a Hidden, Estrogen-Driven Cause of Severe Period Pain
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/08/23/adenomyosis-symptoms-causes-natural-treatment.aspx
Analysis by Dr. Joseph Mercola August 23, 2025
Story at-a-glance
- Adenomyosis is often mistaken for bad period pain or endometriosis, but it involves tissue growing into the uterine muscle, causing swelling, heavy bleeding, and knife-like cramps
- Many women suffer for years without a diagnosis because doctors misinterpret symptoms or rely on outdated assumptions that the condition only affects older women
- Research shows adenomyosis leads to serious complications like infertility, miscarriage, preeclampsia, and dangerously low hemoglobin levels requiring emergency transfusions
- Estrogen overload is the main driver of adenomyosis, and it’s made worse by birth control, plastics, vegetable oils, and hormone-disrupting chemicals found in everyday products
- You can start reversing estrogen dominance naturally by cutting synthetic hormones, avoiding xenoestrogens, restoring metabolism with the right carbs, and using natural progesterone
If your period pain feels unbearable — like a deep, throbbing ache or stabbing cramps that knock the wind out of you — it’s not something to brush off. Pain that severe isn’t normal. For millions of women, it’s the body’s warning signal for something deeper that’s often misunderstood or completely missed.
You’ve likely been told that heavy bleeding, pelvic pressure, and fatigue are just part of being a woman. But what if those symptoms point to a disease that’s quietly hijacking your uterus and flooding your body with inflammation? That’s the reality for countless women who are dismissed, misdiagnosed, or left in the dark for years, sometimes decades. This condition, known as adenomyosis, doesn’t always show up clearly on a scan.
It’s not taught well in medical school. And it’s rarely mentioned in mainstream conversations about women’s health. But it’s there, silently reshaping lives, month after month. I want to walk you through what the research now shows — why it happens, who’s at risk, and what your options actually are. The science is evolving fast, and the data is clear: you don’t have to live like this. Let’s take a look at the overlooked patterns and newest discoveries about this underdiagnosed disease.
Most Women Are Told Their Pain Is Normal — It Isn’t
From the women suffering through debilitating cramps to the doctors mislabeling it as “just a bad period,” an article in The Hearty Soul pulls back the curtain on how widespread yet invisible adenomyosis is.1 It presents differently from endometriosis and takes a devastating toll on a woman’s social life, mental well-being, and ability to function day to day.
• Symptoms often mimic other conditions, which causes many women to go undiagnosed — Unlike endometriosis, adenomyosis causes the uterine wall itself to thicken and expand, sometimes doubling or tripling in size. Women describe the pain as knife-like cramping that strikes during menstruation, along with painful sex, bloating, pelvic pressure, and severe bleeding that disrupts quality of life.
There’s a cultural normalization of these symptoms, but just because menstrual pain is common doesn’t mean it’s normal.
• Doctors often dismiss or misinterpret these symptoms, further delaying diagnosis — Gynecologist Dr. Shamitha Kathurusinghe, who points out that many doctors are themselves misinformed: “There’s a lot of misinformation because there’s a lot of misunderstanding that comes from messaging that doctors are getting.” That means women aren’t just being ignored — they’re being actively misled into thinking their symptoms don’t warrant investigation.
• The lack of awareness creates a cycle of isolation and suffering — Many women miss work, cancel plans, and lose relationships because of the unpredictability and severity of their symptoms. Yet they often remain silent out of embarrassment or fear of being labeled “dramatic.”
• Adenomyosis doesn’t always come with symptoms, making it harder to catch early — The condition is often silent for years, only showing up after other reproductive complications arise. But when it does cause symptoms, it mimics endometriosis or fibroids, which complicates diagnosis and treatment decisions.
Younger Women Are Now at Risk — and Doctors Aren’t Catching It
A review published in the Journal of Clinical Medicine revealed just how often adenomyosis is missed or misunderstood in clinical settings.2 The paper compiled data from dozens of high-quality studies to explore how adenomyosis affects everything from fertility to miscarriage risk. The review focused on women of reproductive age and made clear that current diagnostic and treatment approaches are still not consistent, even among specialists.
• Adenomyosis is now being found in much younger women than previously thought — The conventional view has been that this condition primarily affects women in their 40s or 50s, especially those who’ve already had children.
But the paper highlighted that focal forms of adenomyosis — where lesions are isolated rather than spread throughout the uterine muscle — are now increasingly being diagnosed in women in their 30s and even younger. These women often present with fertility problems or abnormal bleeding, but their symptoms are dismissed or misattributed to something else.
• There’s a strong link between adenomyosis and pregnancy complications — Women with adenomyosis have a much higher risk of miscarriage, preterm birth, preeclampsia (dangerously high blood pressure during pregnancy), and delivering babies that are smaller than normal for their gestational age.
These risks are especially pronounced when the adenomyosis is diffuse, meaning it spreads across a wider area of the uterus rather than being confined to one spot. This type of tissue growth interferes with the placenta’s ability to attach and develop normally.
• Even though diagnostic tools exist, global guidelines are still not aligned — so your doctor’s advice may depend on where you live — While some countries are adopting advanced classification systems based on imaging criteria, others still lack a formal system to define or grade adenomyosis severity. That means two women with the exact same symptoms often get completely different diagnoses and treatments depending on which clinic or country they visit.
• The biological explanation lies in how the tissue invades the uterine muscle and disrupts its structure — Researchers believe that tissue from the uterine lining becomes embedded in the muscle wall either through mechanical injury — such as from surgery — or through a faulty junction between the endometrium and the myometrium — the inner and outer layers of the uterus.
Once this tissue is inside the muscle, it thickens and swells with each menstrual cycle, causing inflammation, scarring, and impaired uterine function.
• Several theories explain how adenomyosis starts, but most point to a breakdown in your uterine architecture — One theory, called tissue injury and repair, suggests that repeated damage to the uterine lining causes abnormal healing responses, leading to invasion of the muscle by uterine lining cells.
Another theory proposes that stem cells in the uterus misfire and turn into the wrong kind of tissue, embedding themselves where they don’t belong. In either case, the result is the same: a uterus that’s constantly inflamed, structurally compromised, and metabolically inefficient.
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Adenomyosis Isn’t Just Painful — It Leads to Emergency Room Visits
An overview from Johns Hopkins Medicine highlights how adenomyosis becomes medically dangerous, not just inconvenient or uncomfortable.3 While the condition is often brushed off as a heavy period, the article makes clear that some women bleed so much they end up severely anemic, requiring blood transfusions just to restore basic function.
Gynecologic oncologist Dr. Mildred Chernofsky explains that adenomyosis involves tissue that grows into the muscular wall of the uterus and bleeds every month like normal uterine lining. But because it’s trapped in the muscle, it causes inflammation, swelling, and massive blood loss.
• The most severe cases involve hemoglobin levels dropping to life-threatening lows — According to Chernofsky, “I may see patients that bleed until they have a hemoglobin level of 7 grams per deciliter and are extremely anemic.” Normal hemoglobin levels for women range from 12 to 16 g/dL. When blood levels drop this low, women often experience fatigue, dizziness, fainting, shortness of breath, and lightheadedness.
• Most women don’t even realize their uterus has enlarged until the symptoms are advanced — The uterus becomes spongy, heavy, and balloon-like. This bloating feels like constant pressure in your lower abdomen or a sense of fullness that doesn’t go away. Yet during physical exams, doctors often don’t recognize the warning signs unless they specifically palpate the uterus and check for size, shape, and density irregularities.
• Diagnosing adenomyosis still depends heavily on imaging, and MRI remains the most accurate tool — While an ultrasound is usually the first step, it’s not always sensitive enough to pick up on deeper tissue invasion. “MRI provides incredibly high-resolution images and shows us the thickness of the endometrial-myometrial junction,” says Chernofsky. That junction — the boundary where the uterine lining meets the muscle — is usually where the disease starts.
• Adenomyosis often gets confused with two other conditions: endometriosis and fibroids, but the treatments are different — While all three cause pelvic pain and heavy bleeding, they originate in different tissues and require different approaches. Endometriosis involves tissue outside the uterus. Fibroids are benign tumors. Adenomyosis, on the other hand, is diffuse tissue growth inside the uterine wall, and can’t simply be “cut out” the way fibroids sometimes are.
• Surgery is often used as a last resort — Unlike fibroids, adenomyosis tissue spreads throughout the uterus and often has fingerlike projections that invade the muscle. That makes it difficult to remove piece by piece. This means that for women with severe, unrelenting symptoms, removing the uterus becomes conventional medicine’s go-to permanent solution.
How to Stop Feeding the Root Cause of Adenomyosis
If you’ve been dealing with symptoms like heavy bleeding, intense cramping, or a constantly bloated abdomen — and you suspect or know you have adenomyosis — then it’s time to focus on the root of the issue: excess estrogen. Estrogen dominance fuels this disease.4 That includes both the estrogen your body produces and the synthetic or food-based estrogens you’re exposed to without realizing it.
You’re not powerless here. You can start taking control today. The goal is to block what’s driving this disease while rebuilding your energy and restoring balance. If you’re looking to avoid hormonal treatments like birth control pills or you’re looking for alternatives to surgery, these five steps will help you move forward.
1. Cut off the estrogen at the source — If you’re on birth control or hormone replacement therapy, and you’re dealing with adenomyosis symptoms, those drugs are likely making things worse. Synthetic estrogens increase tissue growth inside your uterus.5
You’ll also want to stay far away from plastics, conventional cleaning products, and chemical-laden beauty products — these all contain xenoestrogens, which mimic estrogen in your body. Switch to glass containers, and use natural or homemade personal care and cleaning options.
2. Use natural progesterone to block the damage — Natural progesterone is your anti-estrogen. It doesn’t just relieve symptoms — it actually blocks the effects of both estrogen and cortisol. That’s a powerful combination. But don’t rush into it. If your diet is still holding you back from making energy at the cellular level, progesterone won’t have its full effect. First, rebuild your metabolic foundation.
Once your diet supports mitochondrial energy production, introducing a natural progesterone, as described below, makes a noticeable difference.
3. Fix your metabolism with the right carbs — not fewer — If you’ve been doing keto or low-carb, stop. Shift toward 250 grams of carbs per day, and more if you’re very active. This is what your cells need to make adenosine triphosphate (ATP), the fuel that powers everything from brain function to hormone balance.
Start with white rice and whole fruit. Add well-cooked root vegetables next. Hold off on raw greens, whole grains and beans until your gut is healthy, meaning your bowel habits, bloating, and overall comfort are under control.
4. Filter your toxins, especially vegetable oils — Linoleic acid (LA), the dominant fat in vegetable oils, mimics estrogen, contributing to estrogen dominance. As a result, LA disrupts hormonal balance along with mitochondrial function. Cut out all forms of vegetable oils, including from processed foods, restaurant meals, and even nuts and seeds. Replace them with tallow, grass fed butter, or ghee.
5. Know your prolactin level — Many people believe they’re low in estrogen due to bloodwork, when they actually have high levels in their organs. This is because serum estrogen levels are not representative of estrogen that’s stored in tissues. Estrogen is often low in plasma but high in tissues. Prolactin levels serve as a reliable indicator of estrogen activity, as estrogen directly stimulates your pituitary gland to produce prolactin.
When prolactin levels are elevated, it signals increased estrogen receptor activation, whether from your body’s own estrogen production or environmental exposures to endocrine-disrupting chemicals in microplastics and other pollutants. This relationship is particularly significant when combined with low thyroid function, making prolactin an important marker for identifying hormonal imbalance.
FAQs About Adenomyosis
Q: What is adenomyosis and how is it different from other conditions like endometriosis or fibroids?
A: Adenomyosis is a condition where the tissue that normally lines your uterus grows into the muscular wall of the uterus itself. This causes the uterus to swell and leads to intense cramps, heavy bleeding, and chronic pelvic pain. Unlike endometriosis (where tissue grows outside the uterus) or fibroids (benign tumors), adenomyosis spreads through the uterine muscle and can’t be removed surgically in the same way.
Q: Why do so many women go undiagnosed with adenomyosis?
A: Doctors often misinterpret adenomyosis symptoms or attribute them to other conditions. Symptoms like painful periods, bloating, and fatigue are frequently dismissed as “normal,” especially in younger women. Additionally, imaging tools like ultrasound don’t always catch the disease. MRI is more accurate but less commonly used, so many women are left undiagnosed or misdiagnosed for years.
Q: What are the long-term risks of untreated adenomyosis?
A: Left untreated, adenomyosis often leads to severe anemia from chronic blood loss, requiring emergency care or blood transfusions. It also increases the risk of pregnancy complications, including miscarriage, preeclampsia, and preterm birth. Over time, the ongoing inflammation and uterine damage leads to reduced fertility and significant declines in quality of life.
Q: What is the root cause of adenomyosis and how do I address it?
A: The underlying driver of adenomyosis is excess estrogen, including both natural estrogen and environmental estrogens from plastics, chemicals, and synthetic hormones. To lower your estrogen load, cut out vegetable oils and processed foods, reduce chemical exposures and birth control pills, use natural progesterone and support your metabolism through strategic dietary shifts and mitochondrial repair.
Q: What steps can I take today to start feeling better?
A: Start by eliminating hormone disruptors like synthetic birth control and chemical-laden products. Shift to a higher-carb, whole-food diet to rebuild your mitochondrial function. Add natural progesterone and monitor prolactin levels to get a more accurate picture of your true estrogen burden and hormonal balance.
Linoleic Acid, Mitochondria, Gut Microbiome, and Metabolic Health — A Mechanistic Review
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/07/21/linoleic-acid-mitochondrial-damage-metabolic-health.aspx
Analysis by Dr. Joseph Mercola July 21, 2025
Story at-a-glance
- Linoleic acid (LA), a fat found in vegetable oils, accumulates in your tissues and disrupts mitochondrial function, which drains your energy and slows your metabolism
- This fat becomes toxic when oxidized, producing harmful byproducts that damage DNA, enzymes, and the machinery your cells need to generate energy
- Excess LA damages your gut by interfering with colon cell metabolism, harming beneficial microbes, and promoting inflammation linked to insulin resistance and obesity
- LA’s half-life in body fat is about two years, meaning the damage builds up slowly and requires long-term dietary changes to reverse
- Cutting out vegetable oils, eating gut-repairing whole foods, and switching to stable fats like grass fed butter and tallow are key steps to restoring your metabolic health
A century ago, linoleic acid (LA) wasn’t a major part of the human diet. Today, it dominates. Hidden in nearly every processed food and most restaurant meals, this polyunsaturated fat — found in vegetable oils like soybean, corn, and canola — has quietly become the most consumed fat in the modern world.
You’ve likely been told it’s healthy, even essential. But the truth is, LA behaves very differently inside your body than other fats. Unlike saturated fats, it’s chemically unstable. It breaks down easily, especially when exposed to heat, light, or oxygen — turning into toxic byproducts that your body struggles to clear. And unlike fats your body uses for energy, this one gets stored in your tissues and builds up over time, where it quietly interferes with energy production, gut health, and hormone regulation.
If you’ve been dealing with low energy, unexplained weight gain, or insulin resistance, there’s a good chance this hidden ingredient is working against you. Most people don’t realize that the foods they’ve been told are heart-healthy, like certain oils, nuts and packaged snacks, are loading their cells with something they weren’t designed to handle in such high amounts.
In my mechanistic review, published in Advances in Redox Research, I broke down exactly how LA disrupts your mitochondria — the energy engines inside every one of your cells.1 What the research revealed changed how I look at metabolic disease entirely.
Too Much LA Throws Your Metabolism Into Chaos
My paper looks closely at how high intake of LA disrupts mitochondrial function, damages gut balance, and triggers insulin resistance.2 It’s a mechanistic review, meaning it synthesizes a wide range of cellular, biochemical, and metabolic evidence to show exactly how LA breaks energy production inside your cells.
The figure above shows how your mitochondria get thrown off balance when making energy. When there’s too much fuel coming in, it overloads your system and causes a backup at key points called Complex I and II. This leads to reductive stress, where electrons leak out and create harmful byproducts like reactive oxygen species (ROS).
On the flip side, if the system is damaged or can’t keep up, “oxidative stress” occurs, also producing harmful waste. Both situations disrupt energy flow and increase the risk of cell damage. The figure highlights the importance of keeping this process in balance for healthy energy production and overall cellular function.
• LA does damage in two directions at once — I detailed how LA creates both oxidative and reductive stress. Oxidative stress is when your body produces too many free radicals. Reductive stress, by contrast, is when your cells build up too many unused electrons because the mitochondria can’t process them fast enough. This combination wrecks the redox balance that your body depends on to generate clean, efficient energy.
• The damage starts at the mitochondria — your body’s energy centers — LA embeds itself into a special fat called cardiolipin, found in the inner membrane of your mitochondria. Cardiolipin holds energy-generating protein complexes together, kind of like scaffolding. But LA is chemically unstable and easily oxidized.
Once inside cardiolipin, it sets off chain reactions that weaken mitochondrial structure, unravel protein complexes, and reduce adenosine triphosphate (ATP) output — your body’s core energy currency.
• Reductive stress quietly sabotages your energy long before symptoms appear — When your diet contains too much LA — from fried foods, processed snacks, salad dressings, and even “healthy” nuts, pork and chicken — it leads to constant overloading of the mitochondria with electrons.
The problem is that the mitochondrial transport chain can’t keep up. Electrons back up and spill over, generating ROS and worsening oxidative damage. This imbalance is a hidden engine behind fatigue, weight gain, and poor metabolic flexibility.
Why Macronutrient Balance Matters for Redox Health
The figure above illustrates how the balance of protein, carbs, and fat in your diet help protect your mitochondria from the kind of energy overload LA creates. The example in the figure uses a common ratio — about 15% protein, 55% carbs, and 30% fat — to demonstrate how a balanced mix of macronutrients keeps your metabolism running smoothly.
• Carbs and fats take different pathways to get broken down for energy, but both eventually fuel your mitochondria — As they’re processed, they generate molecules that feed electrons into your mitochondria to make ATP. If you eat too much of any one macronutrient — especially fat — it overwhelms the system. Your mitochondria can’t process the excess electrons fast enough, creating a traffic jam that leads to reductive stress and oxidative damage.
• When your diet is more balanced, energy flows through your mitochondria in a steadier way — This reduces the risk of cellular stress and improves metabolic flexibility. This helps explain why even high-fat diets marketed as “healthy” backfire if they’re rich in unstable fats like LA — they push your mitochondria past their limit.
• LA doesn’t just sit in your tissues — it poisons your energy over time — Unlike other fats that your body burns or clears quickly, LA sticks around. It builds up in your fat stores and stays there for years, literally. As noted in my review, the half-life of LA in body fat is estimated to be two years. That means every meal high in LA adds to a long-term problem that your body can’t easily reverse.
• LA pushes your system into dysfunction — While LA is essential in small amounts, excessive intake, over time, floods your mitochondria with reactive molecules. When the supply of electrons from fat breakdown exceeds the mitochondria’s capacity to use them, your energy system crashes from the inside out. The result is poor glucose handling, inflammation, and insulin resistance — what many people chalk up to aging, but is actually preventable damage.
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Your Mitochondria Need These Nutrients to Run
The table above shows the essential nutrients your mitochondria need to turn food into usable energy. These include key B vitamins like niacinamide (B3), thiamine (B1), and riboflavin (B2), which act like spark plugs in your cellular engine. They help fuel the chain of reactions that powers ATP production.
• It also includes CoQ10, a compound your body makes but needs more of as you age or if you take statin drugs — CoQ10 helps shuttle electrons inside your mitochondria and reduces oxidative stress.
• Magnesium plays a starring role too — Magnesium helps stabilize ATP and supports hundreds of enzymes involved in metabolism and insulin sensitivity.
• The nutrient amounts listed in the table are general estimates — Your specific needs depend on your diet, health history, and how much stress your system is under. Making sure you get enough of these cofactors helps restore mitochondrial balance and improves how your body handles energy.
Cardiolipin — Your Energy Stabilizer — Gets Hijacked by LA
Cardiolipin isn’t just any fat. It’s unique in structure and key for keeping your mitochondria’s inner membrane stable.
The figure above shows where cardiolipin lives inside your mitochondria and why it matters for energy production. On the left, you see a simplified diagram of a mitochondrion, highlighting its key parts: the outer membrane, inner membrane, the folds called cristae, and the inner space known as the matrix. In the center, the zoomed-in view of the inner membrane points out spots rich in cardiolipin (marked in magenta), especially around the curved edges of the cristae.
These areas help keep the mitochondrial folds stable and support the formation of energy-producing protein clusters. On the right, the figure compares a typical fat molecule with cardiolipin. Unlike regular fats that have two tails, cardiolipin has four, giving it unique properties that help hold proteins in place, keep the membrane flexible, and power essential energy processes. This figure helps explain why cardiolipin is so important for keeping your mitochondria — and your cells — running smoothly.
My review shows how LA infiltrates cardiolipin and makes it highly vulnerable to oxidation. Once oxidized, cardiolipin can’t hold the mitochondrial protein complexes together anymore. This instability ruins the structure needed for ATP production and accelerates cellular aging.
• This process explains why many “healthy” high-fat diets fail over time — While keto or very low-carb diets often seem to work at first by lowering blood sugar, the LA-rich fats they rely on overload your cell “engines.” Breaking down these fats floods your mitochondria with more fuel molecules than they can handle, clogging the energy-production system, slowing ATP creation, and ramping up internal wear-and-tear.
• Once LA oxidizes, it turns into something far more dangerous — The figure above shows how eating too much LA sets off a chain reaction that damages your mitochondria and drains your energy. When you eat a lot of LA, it gets built into the inner membrane of your mitochondria, the part of your cells that makes energy. But LA is fragile. Under stress — especially when your mitochondria are overloaded and energy flow backs up — LA starts to oxidize.
When LA breaks down inside your body, it doesn’t just disappear — it turns into harmful byproducts. One of the worst is called 4-HNE, a sticky, reactive compound that latches onto important parts of your cells like enzymes, DNA, and the machinery inside your mitochondria. Think of it like grease gumming up an engine. It clogs the system that helps your cells make energy. Over time, this damage builds up, draining your energy and stressing your cells even more.
Your Gut Suffers Too, Starting with Your Colon Cells
The figure above shows what happens when your gut microbiome is in balance — and what happens when it’s not. On the left, you see a healthy gut filled with diverse, friendly bacteria that break down fiber into short-chain fatty acids (SCFAs) like butyrate. These compounds feed the cells lining your colon, strengthen your gut barrier, reduce inflammation, and support better blood sugar control. This is how fiber is supposed to work when your gut is healthy.
• LA triggers a cascade that increases inflammation from your gut outward — The right side of the figure tells a different story — one that starts with too much LA in your diet. LA interferes with the ability of colon cells to burn butyrate for fuel, which leaves more oxygen in your gut.
That extra oxygen disrupts the environment, harming helpful bacteria and allowing harmful ones to take over — a condition called dysbiosis. In this inflamed state, the same fiber that normally helps you actually makes things worse by fueling the wrong microbes.
• As dysbiosis deepens, harmful bacteria flourish — They produce toxic byproducts like lipopolysaccharide (LPS), which break through your gut lining and enter your bloodstream. This triggers your immune system, leading to chronic, low-grade inflammation.
Over time, this inflammatory cascade makes insulin resistance worse and raises your risk for problems like fatty liver, obesity, and diabetes. This is known as the fiber paradox — where fiber’s benefits depend entirely on the state of your microbiome.
Insulin Resistance Becomes Inevitable When LA Is High
The table above shows the main tools used to measure insulin resistance and check how well your cells are managing their internal energy chemistry, known as redox balance. One common method is HOMA-IR, a calculation based on fasting insulin and glucose levels that gives a rough idea of how sensitive your cells are to insulin. While it’s convenient for everyday use, it’s not as precise as the gold-standard glucose clamp test, which measures exactly how well your body clears sugar under controlled conditions.
• The table also lists blood markers that reflect how your mitochondria are handling energy — These include ratios like lactate to pyruvate and others that show the balance between NAD⁺ and NADH — a key part of your cell’s energy-making process. When this balance is off, it signals redox stress and early signs of metabolic trouble.
• This is where LA comes in — When your diet is high in LA, it disrupts how your mitochondria produce energy. As that process breaks down, your cells stop responding to insulin the way they should. Your pancreas makes more insulin to compensate, but that only makes things worse. Blood sugar rises, fat starts to build up, and your cells become more inflamed and energy-starved — a downward spiral triggered by too much LA.
Cutting Out LA Helps Restore Your Mitochondria
For more details on the risks of excessive LA intake, read the simplified version of my review. If your energy’s been crashing, your metabolism feels stuck, or your gut hasn’t been right in years, there’s a good chance vegetable oils are part of the problem. You don’t need a lab test to confirm it — just look at what’s in your pantry or what you’ve been eating out.
Getting rid of the LA that’s buried in so many processed foods is the first and most important step to undoing the metabolic damage and giving your cells a chance to function normally again. Here’s what I recommend you do to take back control:
1. Ditch vegetable oils completely — The most direct way to reverse mitochondrial dysfunction is to stop the flood of LA coming in every day. That means eliminating all vegetable oils like soybean, corn, sunflower, safflower, cottonseed, grapeseed, canola, rice bran and peanut oil.
These are hiding in nearly every processed food, packaged snack, and restaurant meal, especially fried foods and dressings. Start reading labels, cook at home more, and treat every elimination as an investment in your energy.
2. Switch to safe fats that don’t damage your mitochondria — Your body needs fat to function — you just need the right kind. Replace those unstable omega-6 fats with stable, saturated fats like grass fed butter, ghee, beef tallow and coconut oil. These fats resist oxidation, don’t overload your mitochondria with electrons, and help restore proper redox balance inside your cells. I use them regularly because they support energy, hormones, and brain health without contributing to inflammation.
3. Eat more foods that repair your gut and feed your colon cells — If your gut’s been compromised by LA, you’ll want to focus on foods that restore the oxygen balance in your colon and support butyrate production. High-quality carbs like sweet potatoes, carrots, squash, and rice are rich in fermentable fibers that fuel this process. But here’s the catch: as mentioned, if your gut is already damaged, throwing in lots of fiber too soon will make symptoms worse. That’s the fiber paradox.
If you’re struggling with bloating, cramping, constipation or loose stools, start by healing your gut first — then introduce fiber-rich foods slowly, in small amounts. Once tolerated, these fibers help reinforce your gut lining, lower inflammation, and recalibrate your immune system. You’ll feel the difference in everything from digestion to energy and mood.
4. Cut back on olive oil, nuts and seeds — even the so-called healthy ones — Nuts and seeds are often seen as health foods, but many, like walnuts, almonds, pecans, sunflower, and pumpkin seeds — are loaded with LA. Even macadamia nuts and olive oil, while lower in LA, are rich in monounsaturated fats that oxidize easily under heat or light.
That oxidation stresses your mitochondria and disrupts energy production. Olive oil is also commonly adulterated with cheaper vegetable oils. If you snack on nut butters or drizzle olive oil over everything, it’s time to rethink those habits.
5. Stay consistent, because LA takes years to clear — This isn’t something you fix in a week. Since LA has a half-life of about two years, it means the fats stored in your tissues now will still affect your mitochondria years from today. But every LA-free meal you eat moves you forward.
Every time you say no to fried foods, chips, or commercial salad dressing, you’re giving your cells a break and slowly offloading the oxidative burden. Think of this like a slow, steady cleanup — each step compounds and helps rebuild your metabolism from the inside out.
FAQs About Linoleic Acid
Q: Why is LA considered harmful if it’s labeled as “heart-healthy”?
A: While LA is essential in small amounts, modern diets overload your body with it, mainly from vegetable oils. In excess, LA embeds itself in your mitochondria, oxidizes, and creates toxic byproducts that damage energy production, promote inflammation, and drive insulin resistance.
Q: What are the signs that LA is damaging my metabolism?
A: If you experience chronic fatigue, weight gain, blood sugar issues, gut problems, or difficulty losing fat despite a healthy diet, LA could be a hidden factor. It accumulates in your fat tissue, disrupts mitochondrial function, and lingers in your body for years, slowing energy output and triggering inflammation.
Q: How does LA affect gut health?
A: LA interferes with the metabolism of colon cells, which alters the gut environment by raising oxygen levels, harming beneficial microbes and favoring the growth of harmful bacteria. This shift leads to dysbiosis and increases the production of inflammatory compounds that breach your gut lining and enter your bloodstream, contributing to systemic inflammation.
Q: What foods should I avoid to lower my LA intake?
A: Steer clear of vegetable oils like soybean, corn, safflower, sunflower, and canola oils. Also limit high-LA foods such as processed snacks, fried foods, salad dressings, and even chicken, pork, nuts, seeds, and olive oil.
Q: How long does it take to get LA out of my body?
A: LA has a half-life of about two years, so it takes time to clear. However, every LA-free meal you eat helps reduce your oxidative burden, improve mitochondrial function, and restore metabolic health day by day.
Inflammation Alters Mood and Behavior
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/05/10/inflammation-alters-mood-and-behavior.aspx
Analysis by Dr. Joseph Mercola May 10, 2025
STORY AT-A-GLANCE
- New research shows inflammation directly influences mood and behavior by sending chemical signals that activate anxiety circuits in the brain, helping to explain emotional aftereffects of illness
- Specific inflammatory cytokines stimulate neurons in brain regions responsible for processing fear, while anti-inflammatory signals calm these same neural pathways
- Scientists discovered that certain immune molecules function like neurotransmitters in the brain, influencing social behavior and emotional states independently of inflammation
- Blocking inflammation incorrectly backfires; it triggers more intense anxiety as the body produces additional inflammatory messengers that overstimulate fear circuitry
- Managing inflammation-related mood issues requires reducing linoleic acid (LA) intake from vegetable oils, supporting mitochondrial function, getting safe sun exposure, avoiding alcohol and monitoring emotional symptoms after illness
After a physical illness, emotional aftershocks are more common than most people realize. Mood swings, irritability and even social withdrawal often surface without warning — and they don’t always go away when the fever breaks or the rash fades. These shifts are frequently dismissed as psychological or stress-related, but there’s more going on under the surface.
Emerging science is redefining how we understand these post-illness changes. Rather than being side effects of recovery, they appear to be part of a complex feedback loop between your immune system and your brain. It’s not just about fighting infection. Your body is sending signals that shape how you feel, how you think and how you connect with others.
For years, the biological link between the immune response and emotional state was a mystery. Doctors observed the patterns but lacked a clear explanation for why recovering patients often reported feeling emotionally unwell. That’s beginning to change.
Recent research is uncovering exactly how immune activity interacts with brain circuits involved in mood and behavior, offering new clues — and new hope — for addressing anxiety, depression and social disconnection at the source.
A set of studies, published in Cell in April 2025, offers a detailed look at this immune-brain connection.1,2 These findings move us beyond theory and into practical understanding of how immune molecules affect your emotional wiring in real time.
Inflammation Hijacks Your Brain’s Anxiety Center
The first study investigated how inflammation affects anxiety by mapping how immune molecules called cytokines interact with brain circuits.3 The researchers focused on two inflammatory signals and how they stimulated neurons in a region of the brain responsible for processing fear and emotional memories. In animal models, the team looked at how changes in immune activity led to shifts in anxiety-related behaviors.
• Researchers identified brain cells that react to both pro- and anti-inflammatory signals — The key discovery was that certain brain cells respond to both types of immune messengers. These cells are constantly listening for cues. If the message is inflammatory, anxiety circuits rev up; if the message is anti-inflammatory, those same circuits calm down. Your mood, in other words, is closely tied to which immune signals your brain is getting at any given time.
• The findings explain why you feel more anxious during or after illness — When inflammatory cytokines rose, mice became more anxious. They avoided open spaces, explored less and showed clear signs of being on edge. Even more surprising, when researchers tried to block these inflammatory signals, it made things worse. The body responded by producing even more inflammation, which overstimulated the brain’s fear circuitry.
• Blocking inflammation the wrong way triggered rebound anxiety — In the study, interfering with inflammatory signaling didn’t reduce anxiety — it backfired. The body overcorrected by flooding the system with more inflammatory messengers, creating even more excitability in fear-processing neurons. This highlights how delicate the system is and why simply trying to “shut off” inflammation won’t work without understanding the underlying balance.
Calming Signals Work Through the Same Brain Pathway
The same brain cells that react to inflammatory signals also respond to anti-inflammatory cues. When those calming signals were increased, the anxious behavior disappeared. The mice became calmer, more balanced and less reactive to their environment. These results show that your immune system has its own internal checks and balances — you just have to support them.
• One calming molecule suppresses anxious brain activity — A specific anti-inflammatory signal works like a brake for your brain’s fear response. When this molecule interacts with the neurons in your brain’s anxiety center, it lowers their activity. That makes them fire less often, which slows the brain’s anxiety feedback loop. In other words, your brain becomes less hyperreactive and more emotionally stable.
• These immune messengers act instantly — Your immune system sends out real-time signals that shift your emotional state within minutes. That’s why anxiety often feels like it comes out of nowhere. A spike in inflammation, whether from an infection, injury or stress, changes how your brain behaves almost immediately.
• Fear-processing cells get stuck in overdrive — When inflammatory messengers dominate, the neurons in your brain’s fear center become overly excitable. They start firing too often and too intensely, feeding a loop of anxiety and worry. This makes it harder for your body’s natural calming systems to keep up. Your stress response becomes harder to shut off.
• The same neurons receive both calming and fear signals — The exact same brain cells can be told to panic or to relax, depending on which immune molecule they hear from. If your system is inflamed, those calming signals get drowned out. But if you support your immune balance, those neurons switch back to a more stable, regulated state.
• This is physical, not just psychological — Anxiety isn’t just mental. It’s physical. It’s rooted in your biology, your immune response and the real-time signals your body is sending to your brain. When inflammation is high, your emotional resilience takes a hit. When it’s balanced, your mood stabilizes.
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Cytokines Boost Social Behavior by Acting Like Brain Chemicals
The second study focused on a lesser-known cytokine and how it interacts with specific brain receptors to influence social behavior.4 Researchers wanted to know which immune-related signals show up in the brain and how they affect behavior when triggered. Instead of focusing on how these signals trigger inflammation, the team explored their role as brain messengers — working more like mood-regulating chemicals to shift behavior in real time.
• Researchers identified a brain signal that increases sociability and curiosity — A specific chemical message activates a part of the brain responsible for social behavior. When this signal was triggered, mice that usually avoided others and repeated the same actions over and over began behaving more normally.
They explored their surroundings, showed interest in new mice and became more socially engaged. According to the researchers, this signal helped restore a more natural pattern of social connection.
• This chemical signal is made inside the brain, not just by the immune system — In a major discovery, researchers found that this social signal isn’t just produced by immune cells; it’s also made directly by neurons inside the brain. That’s a big deal, because it puts this molecule in the same category as familiar brain chemicals like serotonin and dopamine. It’s not just reacting to the immune system — it’s helping control mood and behavior from within.
• Your brain and immune system use the same language to control behavior — This finding challenges the old belief that immune signals only work outside the brain. In reality, the brain uses some of the exact same molecules your immune system does — just in a different context.
These shared messages help manage emotional behavior, including how connected, curious or socially withdrawn you feel. In this case, boosting the signal helped correct withdrawn behavior in mice genetically inclined toward social avoidance.
• Cytokines influence emotional state and behavior without needing to enter the brain — One of the most important takeaways from the research is that immune molecules don’t have to cross the blood-brain barrier to affect how you feel. The research showed that cytokines act on brain areas that already receive immune signals.5
These findings are part of a broader effort to understand how your brain and immune system work together — and sometimes against you — to shape your mood.
• Scientists are also questioning how inflammation impacts the blood-brain barrier itself — A lingering question could hold the key to better treatments: Does chronic inflammation weaken the blood-brain barrier, making it more permeable to damaging substances? If so, then long-term inflammation wouldn’t just influence mood temporarily; it could change how vulnerable your brain is to future damage.6
What to Do About Chronic Inflammation That Alters How Your Brain Processes Mood and Behavior
If your anxiety, mood swings or social withdrawal feel worse after getting sick — or seem to come out of nowhere — it’s time to take a closer look at the root cause: chronic inflammation. You don’t fix this by numbing symptoms. You fix it by restoring balance to your immune system and protecting your brain’s delicate communication circuits.
The goal is to stop the runaway signaling that hijacks your emotional centers and rewires your behavior from the inside out. These five steps target the biological triggers, including cytokine signaling, mitochondrial stress and brain inflammation, so you start feeling like yourself again.
1. Cut linoleic acid (LA) down to under 5 grams per day — ideally below 2 — If you only do one thing, make it this. LA in vegetable oils drives inflammation like gasoline on a fire. It hides in nearly every processed food: restaurant meals, sauces, chips, crackers, even “healthy” organic snacks. Swap all vegetable oils for healthier fats like grass-fed butter, ghee or tallow.
Stay away from olive and avocado oil, as they’re often cut with cheaper vegetable oils and still too high in monounsaturated fat, which causes similar mitochondrial dysfunction. I recommend tracking your LA intake for a few days using a free online food tracker. You’ll be shocked by what you uncover.
2. Support your mitochondria by giving them the fuel they actually need — Your mood is tied directly to how much energy your cells produce. Cytokines disrupt this energy flow, which leaves you feeling drained, foggy or emotionally reactive. To repair that, you need to restore production of adenosine triphosphate (ATP), your body’s main energy currency that your cells need to survive and repair.
Start by increasing your carbohydrate intake with easy-to-digest sources like fruit juice with pulp, white rice and whole fruit. If you have unbalanced gut bacteria, or dysbiosis, avoid fiber, including whole grains, until your gut is healed. Ultimately, most adults need about 250 grams of healthy carbs daily. Starving your mitochondria will only prolong the problem.
3. Boost your anti-inflammatory signals naturally with sun exposure — Sunlight helps your cells produce energy more efficiently and triggers your body to make key anti-inflammatory molecules. It also helps regulate mood through melatonin and vitamin D production. But don’t just sunbathe randomly.
The safest and most effective exposure happens after you’ve eliminated seed oils from your diet for at least six months. Until then, stick to morning and late-afternoon light — no harsh midday sun.
4. Avoid alcohol, as it destroys mitochondrial function and inflames your brain — Alcohol is a metabolic poison. Even small amounts disrupt mitochondrial energy production and increase oxidative stress in the brain. The idea that moderate drinking is protective was based on flawed studies. Don’t let marketing override your biology.
5. Watch for delayed emotional symptoms after illness and adjust early — If you’re someone who experiences mood swings after getting sick, or during stressful immune events like a dental procedure or vaccine, start tracking your mood in a journal. Note when symptoms begin, how long they last and what symptoms show up, like irritability, social withdrawal or fatigue.
This helps you link emotional shifts to immune activity and gives you a clear signal when it’s time to double down on your recovery strategies.
The earlier you respond, the faster you recover. When your immune system is in balance, your brain calms down. You think more clearly, connect more easily with others and feel more like yourself again.
FAQs About Inflammation and Mood
Q: How does inflammation affect your mood and behavior?
A: Inflammation sends chemical messengers called cytokines into your bloodstream, some of which directly activate anxiety circuits in your brain. These signals make you feel anxious, withdrawn or emotionally unstable, especially after illness or during immune system flare-ups.
Q: What role do immune signals play in emotional regulation?
A: Some immune signals increase anxiety by overstimulating the part of your brain that processes fear. Others send calming messages to those same brain cells, helping reduce anxious behavior. Your emotional state depends on which of these signals is stronger at any given time.
Q: Can immune signals influence social behavior too?
A: Yes. One specific immune signal was shown to increase social interest and reduce repetitive behavior in mice that typically avoided interaction. What makes it unique is that it’s also produced by brain cells, not just the immune system, so it acts more like familiar brain chemicals such as serotonin or dopamine.
Q: What’s the connection between chronic illness and mood swings?
A: New research shows that mood changes following infections or autoimmune episodes are the result of immune-brain cross talk. Inflammatory cytokines activate specific brain circuits almost immediately, reshaping how you process fear, emotion and social interaction.
Q: What helps lower cytokine-driven mood issues?
A: Start by removing vegetable oils and processed foods that drive inflammation. Support cellular energy with digestible carbs like fruit and white rice. Get safe sun exposure to activate your body’s anti-inflammatory pathways and avoid alcohol, which impairs mitochondrial function and inflames your brain.
How Mitochondria Help Fight Infections and Calm Autoimmune Storms
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/04/22/how-mitochondria-help-fight-infections.aspx
Analysis by Dr. Joseph Mercola April 22, 2025
STORY AT-A-GLANCE
- Macrophages and mitochondria are immune partners; macrophages clear germs and control inflammation, while mitochondria power cells and signal macrophages to manage inflammation effectively
- Mitochondria’s complex III produces superoxide, signaling macrophages to release IL-10, the “off switch” for inflammation — key for preventing chronic and autoimmune issues
- Research showed impaired mitochondrial complex III reduces IL-10, causing unchecked inflammation and severe illness, highlighting mitochondria’s important immune regulatory role
- Naturally boost IL-10 through fiber-rich foods for butyrate, sunshine exposure, exercise and spices like garlic to enhance your body’s inflammation control mechanisms
- Healthy mitochondria, threatened by seed oils in processed foods and toxins, are essential for energy and immunity; lifestyle choices significantly impact mitochondrial function and overall well-being
Your body’s a busy place, full of tiny workers keeping you healthy. Some of these workers, like macrophages and mitochondria, do more than you might think. They’re not just cleaning up germs or powering your cells — they’re also teaming up to control inflammation, that fiery response that protects you from infections in the short term but contributes to diseases when it becomes chronic.
It’s important to understand how these cellular heroes work, why they’re key for fighting infections and calming autoimmune flare-ups, and, perhaps most importantly, how to support them with simple, everyday habits.
Meet Your Body’s Cleanup Crew — What Are Macrophages?
You’ve got a squad of cells called macrophages patrolling your body. Think of them as your cleanup crew — part janitor, part security guard. They roam around, gobbling up germs like bacteria and viruses, and tidying up after cuts or bruises. But they don’t stop there. They also play a big role in managing your immune system’s reaction when trouble hits.
• How do they work? When something invades — like a cold virus — macrophages swoop in to eat it up. They’re your first line of defense, keeping pathogens in check.
• What’s their secret weapon? Macrophages release a helper called IL-10, which is like an “all clear” signal. It tells your immune system to back off once the danger’s gone. This is important because it stops inflammation from going overboard.
Inflammation is like a fire alarm — it’s loud and grabs attention when you need to fight off invaders. But if it keeps blaring after the germ’s gone, it’s trouble. That’s where macrophages and IL-10 save the day, especially for conditions like autoimmune diseases — such as rheumatoid arthritis or lupus, where your body attacks itself — or severe infections like sepsis, a body-wide emergency.
What Are Mitochondria? More Than Just Energy Makers
Inside your cells, you’ve got tiny mitochondria, often referred to as “power plants.” They churn out energy to keep you moving, like batteries powering a city. Macrophages lean on them to fuel their cleanup jobs. But mitochondria do much more than just make energy.
• A hidden superpower — Mitochondria are like command centers, sending signals to guide how macrophages handle infections or injuries. Complex III, part of the electron transport chain, is the star here — it’s like a switchboard operator telling everyone what to do.
• Why this matters — Without these signals, your macrophages can’t do their full job. It’s not just about power — it’s about control. And when that control slips, inflammation runs wild.
So, mitochondria aren’t just keeping the lights on — they’re helping you fight germs and calm things down when the battle’s over.
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What Did Scientists Find About Mitochondria and Inflammation?
In a 2025 study published in Science Advances, researchers tested mice to see how mitochondria help macrophages.1 They interfered with the complex III switch in the macrophages of some mice, breaking it on purpose. Then they gave these mice the flu or a serious infection-like state. Those mice got much sicker than normal ones.
• What went wrong? In the lab, those broken macrophages barely made IL-10 when they got infection signals. Without IL-10, they couldn’t quiet the inflammation alarm — it just kept screaming.
• Meet superoxide — Normally, complex III pumps out a molecule called superoxide, a reactive oxygen species (ROS) that’s like a flare macrophages shoot off to influence the production of IL-10. But with no complex III, there’s no superoxide and no calm-down signal in the form of IL-10. The result? Inflammation takes over. The study reveals how important mitochondria are for your immune system. They’re not just energy makers — they tame inflammation, too.
How Does Superoxide Work? The Firefighter Analogy
Let’s break this down with a picture you can see in your head. Imagine superoxide as a firefighter spotting a blaze — that blaze is inflammation. The firefighter grabs a radio and calls for backup — IL-10, the water truck that douses the flames.
• What happens when it breaks? In those mice with broken complex III, the firefighter’s radio is dead. No call goes out, no water trucks roll in and the fire (inflammation) rages on. That’s why the mice in the study got so sick.
• Energy isn’t the fix — Scientists tried giving the macrophages a backup power source called alternative oxidase. It kept the lights on, but without superoxide, IL-10 still didn’t show up. So, superoxide is a key signaling molecule involved in regulating inflammation in your body.
How Can a Protein Save the Day?
Here’s where it gets interesting. When superoxide couldn’t call for help, researchers found a backup plan: a protein called protein kinase A (PKA). Think of PKA as a stand-in firefighter.
• What did the researchers do? In the lab, they turned on PKA in those broken macrophages. Guess what? It worked. PKA picked up the radio and called for IL-10, calming inflammation even without superoxide.
• Why this matters — This finding hints at new ways to help your immune system when mitochondria stumble. It’s like having a spare key to cool things down when inflammation’s heating up.
Do All Macrophage Jobs Need Superoxide?
Not exactly. Macrophages don’t just fight germs; they also make repairs. The researchers gave some macrophages a “repair” signal called IL-4 to heal tissues instead of battle invaders. Interestingly, broken complex III did not interfere with this job.
• Two modes, one cell — Picture macrophages like a car with two gears:
1. Fighting gear — Takes on infections — needs superoxide to call IL-10.
2. Healing gear — Fixes tissues — runs fine without superoxide.
• What this means — Your mitochondria play different roles depending on what’s needed. Fighting germs? They need that superoxide flare. Healing cuts? They’re good without it. This shows how smart your body is — it’s got backup plans for different tasks.
Why Should You Boost IL-10 Naturally?
More IL-10 means a stronger “off switch” for inflammation. That’s beneficial for your health, especially if you’ve got:
• Autoimmune disorders like multiple sclerosis or rheumatoid arthritis, where your immune system mistakenly attacks healthy body tissue.
• Severe infections, where inflammation often spirals out of control.
• The benefits — Boosting IL-10 helps calm those storms naturally. It’s like giving your cleanup crew a megaphone to shout “all clear” louder and faster.
• How do you do it? You don’t need fancy tools, just simple lifestyle changes to lift your IL-10 levels.
How Does Butyrate Boost IL-10 Naturally?
One superstar for raising IL-10 is butyrate, a short-chain fatty acid your gut bacteria make when you eat fiber-rich foods. It’s beneficial for both your gut and immune system. Growing evidence indicates butyrate increases IL-10 production.2
• What does butyrate do? It boosts complex III’s signaling, so your macrophages shoot off more superoxide flares and call in more IL-10 — like giving your firefighter a megaphone. Butyrate also helps nourish your colon cells, which rely on butyrate as a main energy source.
When these cells get the fuel they need, your gut lining stays strong, lowering the chances of substances such as undigested food, bacteria and metabolic wastes sneaking through into your bloodstream, a condition known as leaky gut. Butyrate’s protective effects are linked to multiple health benefits, including more stable digestion and better immune response.
• How do you get it? To boost butyrate production, eat fiber-filled carbohydrates like fruits on a regular basis. You also get butyrate from certain foods like grass fed butter and ghee, but a key way to increase your supply is by adding fiber sources such as fruits, vegetables, whole grains and beans to your meals. When you give your gut bacteria enough fiber to ferment, they create even more butyrate.
It’s important to understand, however, that if your gut health is poor, increasing dietary fiber must be done gradually to avoid the production of endotoxin, a mitochondrial poison. Rice and whole fruits are a good starting point.
What Are Other Ways to Boost IL-10 Naturally?
Butyrate’s not the only trick up your sleeve to boost IL-10. Here are more easy ways to increase IL-10 and keep your immune system happy:
• Sunshine or ultraviolet B (UVB) light therapy — Exposure to sunlight or UVB light therapy increases levels of IL-10.3 Ideally, expose your bare skin to direct sunlight daily. Be aware, however, that seed oils, rampant in processed and fast food, are packed with linoleic acid (LA).
In the future we will be referring to these fats as PUFs which is short for polyunsaturated fats as it is far more accurate than calling them PUFAs, since most people know them as fats and not acids.
When LA accumulated in your skin interacts with the sun’s UV rays, it triggers inflammation and DNA damage. It’s best to avoid direct sunlight during peak hours (10 a.m. to 4 p.m.) until you’ve cut back on seed oils for six months. This gives your body time to clear some of the accumulated LA.
• Exercise — Getting moving, whether it’s walking, dancing or biking, boosts IL-10. One study found a 27-fold increase in IL-10 immediately after exercise.4
• Spice it up — Try adding these to your meals regularly:
1. Garlic — Toss it in your meals — it’s tasty and helps boost IL-10.5
2. Licorice — Consider sipping it as a tea — but be aware licorice is contraindicated for those with high blood pressure, kidney or liver disease and pregnant and breastfeeding women.6
Why Does Mitochondrial Health Matter to You?
Mitochondria play a key role in producing adenosine triphosphate (ATP), the energy currency essential for numerous cellular functions. When mitochondrial function is compromised, ATP production decreases, leading to cellular energy deficits.
This reduction in energy impairs the cell’s ability to regulate normal processes, fostering an environment ripe for chronic inflammation. If your mitochondria are dysfunctional, you might notice trouble fighting infections, more inflammation and chronic disease.
• What harms mitochondria? LA in most processed foods is a widespread mitochondrial poison that compromises your cellular energy production. Endocrine-disrupting chemicals (EDCs), including estrogen-mimicking compounds like xenoestrogens, and pervasive electromagnetic fields (EMFs) also interfere with your mitochondria and your cells’ ability to generate energy efficiently.
• What helps mitochondria? Along with avoiding LA, EDCs and EMFs, carbohydrates play a key role in supporting your mitochondrial function.
Most adults need a daily intake of around 200 to 250 grams of targeted carbohydrates to support cellular energy. If you lead a more active lifestyle, you likely need even more. If you have dysbiosis, avoid fiber until your gut heals.
If your gut health is generally healthy or you have only minor gut issues, start with easily digestible options like white rice and whole fruits. As your gut adjusts, consider adding root vegetables, then non-starchy vegetables, starchy vegetables like sweet potatoes or squash, beans, legumes and, finally, minimally processed whole grains.
FAQs About Mitochondria and Autoimmune Disorders
Q: What foods boost IL-10 naturally?
A: Fiber-rich foods, including apples, berries, broccoli, sweet potatoes, oats and rice, feed your gut bacteria, which then produce butyrate. Butyrate is a short-chain fatty acid that acts as a “power-up” for your immune system, specifically boosting the signaling of mitochondrial complex III in macrophages.
This enhanced signaling leads to increased superoxide production, which in turn triggers a greater release of IL-10, the anti-inflammatory molecule. Therefore, focusing on incorporating diverse fiber sources in your diet is key to naturally elevating IL-10 levels. One caveat — if you have dysbiosis, avoid fiber until your gut health is healed.
Q: How does exercise help your immune system?
A: Exercise serves as a rapid and potent natural method to enhance your immune system’s ability to manage inflammation. Even a short burst of physical activity, such as walking or dancing, significantly increases IL-10 levels — up to 27 times in one study.7
This surge in IL-10 acts as a powerful “off switch” for inflammation, quickly calming down immune responses. By regularly engaging in physical activity, you’re effectively training your immune system to efficiently resolve inflammation, promoting balance and preventing it from becoming chronic.
Q: Why does IL-10 matter for autoimmune disorders?
A: IL-10 is important in autoimmune disorders because it functions as the immune system’s “off switch” for inflammation. In autoimmune conditions like lupus, rheumatoid arthritis and multiple sclerosis, the immune system mistakenly attacks the body’s own healthy tissues.
IL-10’s role is to signal the immune system to stand down and stop this attack. By effectively promoting the resolution of inflammation, IL-10 provides significant relief in autoimmune disorders by preventing the immune system from continuously harming healthy cells and tissues.
Q: What’s the best way to support mitochondria?
A: Supporting your mitochondria involves several key strategies: dietary fiber intake to produce butyrate, daily physical activity to boost IL-10 and overall mitochondrial function and regular sun exposure (or UVB light therapy) to also increase IL-10. Equally important is avoiding factors that harm mitochondria, such as linoleic acid prevalent in processed foods and seed oils, endocrine-disrupting chemicals and electromagnetic fields.
Further, ensuring adequate targeted carbohydrate intake (200 to 250 grams daily) fuels mitochondrial energy production. Paying attention to gut health and gradually increasing fiber intake is also important for optimal mitochondrial support.
A Closer Look at the Anticancer Properties of Methylene Blue
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/04/19/anticancer-properties-of-methylene-blue.aspx
Analysis by Dr. Joseph Mercola April 19, 2025
STORY AT-A-GLANCE
- Methylene blue has been shown to shrink tumors and slow cancer growth by targeting cancer cell metabolism and energy production
- Photodynamic therapy with methylene blue uses light activation to destroy cancer cells while leaving healthy cells unharmed, making it a more precise treatment option
- Research on ovarian cancer found that methylene blue forces tumors to shift away from their preferred energy source, making them more vulnerable to treatment
- Unlike chemotherapy, methylene blue treatment does not cause significant side effects or toxicity, making it a promising option for patients with drug-resistant cancers
- Proper dosing is important. Just 5 milligrams of pharmaceutical-grade methylene blue per day is enough to reduce cellular stress and support mitochondrial health
Conventional cancer treatments often come with debilitating side effects. For example, chemotherapy and radiation therapy not only target tumors but also damage healthy cells, leaving patients weakened and vulnerable to infections. In an effort to find safer treatment options for patients, researchers are now testing the efficacy of methylene blue — a commonly used dye that enhances cellular energy production — in treating cancer.
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Methylene Blue Photodynamic Therapy Shrinks Tumors
A systematic review published in Frontiers in Pharmacology analyzed the effects of methylene blue in photodynamic therapy for cancer treatment. Researchers reviewed 10 preclinical studies from different countries assessing how methylene blue, when activated by light, impacts tumor growth.
• Methylene blue targets different cancers — The analysis covered different types of cancer, including colorectal tumors, melanoma and carcinoma, highlighting methylene blue’s ability to shrink tumors through a highly targeted mechanism that spares healthy tissue. A total of 133 mice were used, with 59 receiving methylene blue photodynamic therapy and 74 serving as untreated controls.1
• Antitumor properties of methylene blue — The researchers found that methylene blue significantly reduced tumor sizes in seven of the 10 studies, with reductions ranging from 12% to complete tumor elimination.
The largest effects were seen in colorectal cancer models, where tumors shrank by up to 99.9%, while some breast cancer models showed slower tumor progression rather than outright shrinkage. These results show methylene blue has strong anticancer effects, though its impact varies depending on tumor type and drug delivery method.2
• The use of light to fight cancer — Photodynamic therapy relies on methylene blue’s ability to absorb light in the 630 to 680 nanometer wavelength range. When exposed to this specific type of light, methylene blue generates reactive oxygen species (ROS), highly reactive molecules that destroy cancer cells from within.
This process selectively targets tumor cells because methylene blue accumulates in malignant tissue while sparing healthy cells. The review found that this light-activated destruction was particularly effective in skin and colorectal tumors, leading to significant tumor reduction within weeks of treatment.3
New Technology Improves Bioavailability of Methylene Blue
One of the most promising findings involved the use of nanotechnology to enhance methylene blue’s anticancer effects. Five studies included in the review used nanoformulations — tiny carriers designed to improve the drug’s stability and absorption.4
• Increased bioavailability — According to the researchers, the nano-based versions of methylene blue led to even greater tumor reduction than traditional injections. For instance, a breast cancer study using methylene blue-loaded nanoparticles resulted in complete tumor eradication.5
• Experiments in dosages — Tumor response also depended on the number of methylene blue treatments administered. While some studies used a single injection, others administered up to seven doses over time. More frequent treatments generally resulted in greater tumor shrinkage. For example, one carcinoma model that received seven doses showed significantly slower tumor growth compared to models that received only one or two doses.6
• Results are positive, but sometimes inconsistent — While methylene blue photodynamic therapy was effective in most studies, the review noted some inconsistencies. In a few cases, tumors did not shrink but instead grew more slowly than untreated tumors. This was observed in some breast cancer models, where tumor reduction was not as dramatic as in other cancers.
Researchers theorize that this variation is due to differences in how well methylene blue is absorbed in different tissue types. Some cancers may require modifications in dosing, delivery methods or additional combination therapies to enhance treatment effects.7
• Improved antitumor response — Beyond its ability to destroy cancer cells, methylene blue also helps enhance the immune system’s response to tumors. The meta-analysis shows that ROS generated during photodynamic therapy triggers immune activation, helping the body recognize and attack remaining cancer cells.
This immune-boosting effect likely explains why some tumors continued to shrink even after photodynamic therapy sessions ended. However, more research is needed to confirm this mechanism to help improve long-term treatment outcomes.8
• Safe to use — Methylene blue’s safety profile is another advantage noted in the review. Unlike chemotherapy and radiation, which cause widespread damage to healthy cells, photodynamic therapy with methylene blue resulted in minimal side effects in animal models.
The treatment selectively targeted cancerous tissue without causing significant harm to surrounding healthy cells, making it a promising option for patients who cannot tolerate conventional treatments. Additionally, methylene blue is relatively inexpensive, meaning it offers a more affordable alternative to expensive targeted cancer therapies.9
These findings reinforce methylene blue’s growing reputation as a powerful tool in cancer treatment. By leveraging light-activated therapy, this compound offers a way to precisely target tumors while minimizing damage to healthy cells.10
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Methylene Blue Disrupts Cancer Cell Metabolism
In an animal study published in Cancers, a team of Canadian researchers explored how methylene blue affects ovarian cancer growth at the metabolic level. The findings revealed that methylene blue significantly slowed tumor growth, and more importantly, targets cancer cell metabolism, altering how tumors generate energy and making them more vulnerable to destruction.11
• Methylene blue works as a chemotherapy adjunct — The researchers used an ovarian cancer model where human tumor cells were implanted into immunodeficient mice. These particular cells were resistant to carboplatin, a chemotherapy drug commonly used to treat ovarian cancer. This resistance is a major problem in real-world treatment, as many patients eventually stop responding to standard chemotherapy.
The study compared multiple treatment groups — mice receiving methylene blue alone, methylene blue combined with carboplatin, carboplatin alone and an untreated control group. Tumors in the methylene blue group grew significantly slower than those in the control and carboplatin-only groups, demonstrating its effectiveness even against drug-resistant cancer.12
• Cancer cell energy production is affected — Cancer cells thrive on a dysfunctional metabolism known as the Warburg effect, which prioritizes glucose fermentation over normal oxygen-based energy production. This metabolic switch allows tumors to grow rapidly and resist many treatments.
With this in mind, the study found that methylene blue disrupted this process, forcing cancer cells to rely on oxygen-based energy production again. This shift puts immense stress on the tumor cells, making it harder for them to survive and multiply.13
• Mitochondrial genes are targeted — Cancer cells treated with methylene blue had lower expression of key respiratory chain genes, particularly those involved in complex IV, which is responsible for oxygen reduction.
In other words, methylene blue interfered with the tumor’s ability to efficiently process oxygen, further disrupting its energy supply. This effect was much more pronounced in cancer cells than in normal cells, reinforcing methylene blue’s selective action against tumors.14
• Virtually nontoxic — Methylene blue did not cause noticeable toxicity in the test mice. Unlike chemotherapy, which often leads to severe side effects like weight loss and immune suppression, mice receiving methylene blue maintained stable body weight and showed no signs of distress.
This is a critical advantage, as one of the biggest challenges in cancer treatment is balancing effectiveness with patient quality of life. The ability to target tumors without causing widespread damage makes methylene blue an attractive option for future therapies.15
These findings provide strong evidence that methylene blue is not just a photodynamic agent but also a metabolic disruptor in cancer therapy. By forcing tumors to shift away from their preferred energy source, methylene blue makes them more vulnerable to treatment.16
Safety and Dosage Recommendations for Methylene Blue
Based on these findings, it’s easy to fall into the idea that “more is better” when it comes to taking methylene blue for your health. However, don’t fall into this trap. As mentioned in my interview with metabolic health expert Georgi Dinkov, getting the proper dose is important to avoid severe adverse effects. One example is serotonin syndrome — a fatal condition caused by excessive serotonin levels in the brain.
• Contraindications of methylene blue — It is a potent monoamine oxidase type A (MAO-A) inhibitor. This means that when it is combined with a selective serotonin reuptake inhibitor (SSRI) or other serotonergic drugs, your serotonin levels can increase to dangerous levels.
Methylene blue can interact with other medications, too, including other antidepressants and antimalarials, altering their efficacy or causing adverse reactions. In addition, methylene blue is contraindicated for people diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to the risk of hemolytic anemia (a blood disorder wherein your red blood cells break down faster than your body can replace them).
• Your urine will turn blue — Be aware that methylene blue can stain your urine and occasionally, your tongue. While these effects are harmless, it will most likely surprise you when it happens.
• False pulse oximeter readings — High doses can also interfere with pulse oximeter readings, due to its light absorption properties, resulting in falsely low oxygen saturation readings.
• A note for those with kidney damage — If you have severe renal insufficiency, it would be wise to use methylene blue with caution and under close medical supervision as impaired kidney function influences how fast drugs clear from your system.
• Other side effects of methylene blue — Examples include mild and transient gastrointestinal discomfort, such as nausea and diarrhea. While rare, a wide range of allergic reactions, from skin rashes to life-threatening anaphylaxis, can also occur. Headaches and confusion have also been reported. Though less common, cardiovascular effects, such as increased blood pressure and palpitations, could also occur.
• Low doses are better — Methylene blue is better taken at small, daily doses, ranging from 5 to 15 milligrams (mg), according to Dinkov, especially for long-term use. This is the sweet spot for the diverse benefits of methylene blue without increasing your serotonin levels. High doses of methylene blue are generally reserved for therapeutic applications, and even then, it must be done under the supervision of a medical practitioner.
If you’re considering adding methylene blue to your health routine, consult with a knowledgeable medical professional first. Together, you’ll be able to work out the dosage specific to your needs, as well as warn you of potential harmful interactions with any medications you’re currently taking.
My Personal Way of Taking Methylene Blue
When it comes to buying methylene blue, you’ll find three types for sale — industrial-grade, chemical-grade (laboratory-grade) and pharmaceutical-grade.
• Buy pharmaceutical-grade methylene blue — Out of the three, the only one you should ever use is the pharmaceutical-grade variety, ideally in solid, capsule or tablet forms. Avoid liquid solutions of methylene blue as dissolving it in water significantly decreases its effectiveness after 48 to 72 hours.
• Don’t use methylene blue for aquariums — You’ve probably seen methylene blue used in maintaining aquariums. That’s because it contains antifungal, antiparasitic and oxygen-transporting properties. While those benefits also sound enticing for therapeutic usage, this type of methylene blue often contains additional harmful contaminants, even posing serious health risks to your aquatic pets.
Never use methylene blue designed for aquariums or other animal-related applications. To protect your health, always choose pharmaceutical-grade, as it undergoes rigorous testing to confirm it is free from impurities.
• Methylene blue will help with reductive stress — Remember not to over-rely on methylene blue to achieve optimal health. In my own case, I have eliminated my regular intake of methylene blue. I find that my daily walks by the ocean are incredibly helpful in managing reductive stress naturally.
However, during times when I’m unable to take a walk by the beach, I would consider taking 5 mg of methylene blue daily, adjusting to 3 mg if I were 75 pounds lighter in weight, and doing so six days a week.
If you’re considering taking methylene blue for its anticancer (or other metabolic) benefits, visit your doctor first to check if it’s suitable for your case. The reason for this is because the appropriate way to use methylene blue is through a prescription, and misuse will put your health at risk.
Frequently Asked Questions About the Anticancer Potential of Methylene Blue
Q: How does methylene blue help fight cancer?
A: Methylene blue works in two ways — photodynamic therapy and metabolic disruption. In photodynamic therapy, it accumulates in cancer cells and, when exposed to specific wavelengths of light, produces reactive oxygen species that destroy tumors while sparing healthy tissue. It also disrupts the altered metabolism of cancer cells, forcing them to rely on normal oxygen-based energy production, weakening and slowing their growth.
Q: What types of cancer have methylene blue been shown to affect?
A: Studies have demonstrated that methylene blue significantly shrinks tumors in colorectal cancer, melanoma and carcinoma. Research also shows that it slows the growth of chemotherapy-resistant ovarian cancer, making it a promising option for hard-to-treat cases.
Q: Is methylene blue safe to use as a cancer treatment?
A: Unlike traditional chemotherapy and radiation, methylene blue does not damage healthy cells. Animal studies have shown minimal toxicity, no severe side effects and a strong safety profile. However, pharmaceutical-grade methylene blue should always be used, and improper dosages or interactions with certain medications, like SSRIs, should be avoided.
Q: How is methylene blue taken for cancer therapy?
A: The most effective and safest method is pharmaceutical-grade methylene blue in capsule or tablet form, with a standard dosage of 5 mg once daily for mitochondrial support.
Q: Can methylene blue be combined with other cancer treatments?
A: Yes, research shows that methylene blue enhances the effects of chemotherapy drugs like carboplatin. It also strengthens the immune system’s response to tumors, which will help improve long-term outcomes. More studies are needed to determine the best combinations and dosing strategies for different cancer types.
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 Frontiers in Pharmacology, 14:1264961
- 11, 12, 13, 14, 15, 16 Cancers, 2024, 16(2), 355
Melatonin Fights Against Skeletal Muscle Damage Caused by ‘Diabesity’
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/04/02/melatonin-skeletal-muscle-damage.aspx
Analysis by Dr. Joseph Mercola April 02, 2025
STORY AT-A-GLANCE
- Obesity and insulin resistance impair your mitochondrial function. This leads to muscle breakdown, reduced endurance, and worsening glucose control, which further fuels metabolic disease
- A recent study found that melatonin helps combat obesity-driven muscle deterioration by improving mitochondrial function, reducing oxidative stress, and restoring muscle fibers
- Research shows that melatonin boosts brown adipose tissue (BAT) function, which increases calories burned, improves metabolic flexibility, and protects mitochondria from oxidative damage in diabetes and obesity
- Melatonin makes muscles more resilient and efficient, as it optimizes energy expenditure, activates metabolic pathways that regulate energy production and fat oxidation, prevents fat accumulation and increases fatigue-resistant muscle fibers
- Boost your natural melatonin by getting morning sunlight, reducing digital screen use at night, making your bedroom completely dark and doing relaxing activities before bed
Obesity-driven muscle deterioration occurs when mitochondria, the energy-producing centers of your cells, stop working properly. Skeletal muscle requires constant energy, but when insulin resistance sets in, mitochondrial function declines and oxidative stress skyrockets.
As a result, your body loses its ability to efficiently generate energy, while inflammation and free radicals break down muscle fibers faster than they regenerate. Over time, this leads to muscle weakness, reduced endurance, and worsening glucose control, which fuels the very disease that caused the problem in the first place.
With metabolic disease on the rise, solutions that support mitochondrial health are more important than ever. New research published in Free Radical Biology and Medicine1 in February 2025 highlights an unexpected player in this process — melatonin. While this hormone is more commonly known as a sleep regulator, melatonin is also a key factor in preserving muscle function and optimizing energy metabolism at the cellular level.
How Melatonin Supports Muscle Health and Prevents Damage from ‘Diabesity’
The featured study, led by researchers from the University of Granada, Spain, looked at how melatonin influences muscle health in rats with both obesity and diabetes, a condition they referred to as “diabesity.” Researchers aimed to determine if melatonin prevents muscle loss by increasing energy production and improving muscle fibers. They focused on the vastus lateralis, a large leg muscle that helps with movement and stability. The researchers observed that melatonin:2
• Restores muscle fibers lost due to diabetes — After 12 weeks of melatonin supplementation, researchers observed that melatonin increased slow-twitch muscle fibers and reduced fast-twitch fibers. This is important because slow-twitch fibers are more efficient at using oxygen, helping muscles sustain activity longer without fatigue, unlike fast-twitch fibers, which tire more quickly.
• Improves muscle metabolism and efficiency — The researchers also found that melatonin-treated rats had a higher proportion of oxidative muscle fibers, which require less energy to sustain contractions and allow muscles to function more efficiently. This fiber shift means muscles are better equipped for sustained movement and improved endurance capacity, which is important for individuals with metabolic disorders.
• Boosts cellular energy production — The study showed that melatonin improved mitochondria by increasing their ability to convert nutrients into ATP (energy). This means cells produced more ATP while generating less waste. This made muscle cells more energy-efficient and better equipped to handle metabolic stress.
• Protects muscle cells from oxidative stress — In diabetes, mitochondria produce excess reactive oxygen species (ROS), which damage muscle tissue and accelerate aging. Melatonin lowered ROS levels while boosting antioxidant enzyme activity, especially superoxide dismutase (SOD), which neutralizes harmful molecules. This helps protect mitochondrial integrity and prevent muscle breakdown.
• Strengthens muscle cells at a deeper level — Researchers found that melatonin activated key proteins involved in cellular defense and muscle adaptation, helping muscles resist metabolic stress and recover more effectively.
• Enhances fat-burning in muscles — Melatonin improved how muscle cells processed fat by increasing the activity of enzymes that convert fat into energy. This meant muscles used fat more efficiently instead of storing it, which is especially important for people with obesity and diabetes, as poor fat metabolism leads to weight gain and worsens health problems.
• Works even better in females — Female diabetic rats showed greater improvements in oxidative muscle fibers and energy production, suggesting melatonin’s benefits may be influenced by hormones. This could be especially helpful for postmenopausal women at risk of muscle loss and metabolic decline.
• Maintains strength and energy despite diabetes — By improving energy production, fat metabolism, and muscle protection, melatonin helps counteract muscle loss in diabetes and obesity. It supports endurance, strengthens muscle fibers, and reduces cellular stress, making it a powerful tool for muscle health.
This study builds upon years of research from the University of Granada, which has progressively examined how melatonin supports mitochondrial function, muscle composition, and metabolic health.
How Does Melatonin Enhance Fat Burning and Metabolic Health?
A 2021 study conducted by the research team from the University of Granada, published in Antioxidants (Basel),3 was one of the first to investigate melatonin’s role in metabolic regulation. This study focused on brown adipose tissue (BAT). Unlike white fat, which stores energy, BAT burns fat to produce heat, which helps keep the body warm and regulates metabolism.
However, in people with obesity and diabetes, BAT function declines, leading to slower metabolism, increased fat storage, and impaired energy balance. Researchers aimed to see if melatonin could restore BAT’s ability to burn fat efficiently, improve mitochondrial function, and reduce stress inside cells. According to their findings, melatonin:
• Improves how brown fat burns energy — The study found that melatonin increased the efficiency of mitochondria inside BAT, allowing them to generate energy more effectively. This meant cells produced more ATP (the body’s main energy currency) while wasting less energy.
• Boosts calorie-burning capacity — Melatonin increased levels of UCP1, a protein that turns on BAT’s calorie-burning function. With higher UCP1 activity, BAT cells burned more fat for fuel, helping to improve overall metabolism. Additionally, melatonin increased the number and activity of mitochondria in BAT, further enhancing its ability to burn calories and regulate body temperature.
• Protects brown fat from cellular damage — In metabolic diseases like diabetes, cells produce high levels of harmful ROS, which damage mitochondria and make fat-burning less efficient. The study found that melatonin reduced oxidative stress by boosting antioxidant enzyme activity, which helped neutralize harmful molecules and preserve BAT’s fat-burning function.
• Improves metabolic flexibility — Healthy metabolism depends on your body’s ability to switch between burning fat and glucose for energy, depending on demand. In diabetes, this flexibility is often lost, making it harder to burn stored fat. Melatonin helped restore this ability in BAT, making it easier for the body to balance energy use and prevent insulin resistance.
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How Melatonin Increases Mitochondrial Health and Muscle Composition
Building on these results, a 2023 study also published in Antioxidants (Basel)4 by the same research group shifted the focus from BAT to skeletal muscle, your body’s primary site for movement, strength, and glucose use. They investigated whether melatonin could restore muscle energy production, improve endurance, and protect against muscle deterioration, and found that it:
• Helps muscle cells produce energy more efficiently — Melatonin helped mitochondria maintain their normal function by regulating fission (splitting) and fusion (merging), two processes that keep mitochondria healthy. This prevented energy breakdown and kept muscle cells working more efficiently.
• Activates key muscle-protective enzymes — Melatonin activated SIRT1, an enzyme that shields muscle cells from oxidative stress and improves endurance-based muscle fibers. This means muscle tissue was better protected from the harmful effects of diabetes, reducing fatigue, and preserving strength.
• Promotes cellular renewal — In diabetes, damaged mitochondria accumulate inside muscle cells, making them weaker and more prone to breakdown. The study found that melatonin stimulated autophagy, a process where muscle cells remove damaged mitochondria and replace them with new, fully functional ones. This kept muscle cells stronger, healthier, and more resilient over time.
• Increases fatigue-resistant muscle fibers — Skeletal muscle contains different types of fibers, some designed for quick bursts of energy (fast-twitch fibers) and others for endurance (slow-twitch fibers). The study found that melatonin increased the proportion of oxidative muscle fibers (Type I and Type IIa), which are better at using fat for fuel and resisting fatigue. This means muscles could sustain activity for longer without becoming exhausted.
These findings reinforced the idea that melatonin plays an essential role in supporting skeletal muscle metabolism, improving endurance capacity, and protecting against muscle degeneration in metabolic disorders.
Melatonin Optimizes Energy Expenditure and Prevents Fat Storage
A 2024 study published in Biomedicine and Pharmacotherapy5 expanded upon these findings, combining insights from both skeletal muscle and brown fat studies to investigate melatonin’s broader metabolic effects. Researchers explored how melatonin activates key metabolic pathways that regulate energy balance, endurance and mitochondrial biogenesis (the process of creating new mitochondria). Their findings showed that melatonin:
• Stimulates muscle cells to burn extra energy instead of storing it as fat — Melatonin increased levels of sarcolipin (SLN), a protein that prevents muscles from storing excess energy. Instead, SLN forces muscle cells to burn extra energy as heat rather than storing it as fat, helping to reduce fat buildup while increasing energy expenditure.
• Activates key energy-regulating pathways — Researchers discovered that melatonin turned on a metabolic system that helps muscles generate energy, burn fat, and build stronger mitochondria. This activation enhances the body’s ability to generate sustained energy and resist metabolic stress.
• Improves muscle metabolic efficiency — Skeletal muscle in melatonin-treated rats showed higher mitochondrial function, making muscles more resistant to fatigue and better equipped to handle metabolic stress.
• Prevents fat buildup even without diet or exercise changes — One of the most striking findings was that melatonin led to significantly lower visceral fat storage, even without changes in food intake or physical activity. This suggests that melatonin increases energy expenditure, making the body burn more calories at rest while improving the ability to switch between burning fat and glucose.
This study provided even more evidence that melatonin is a key regulator of metabolism, not just a sleep hormone. To learn more about the role melatonin plays in your health, read “What You Need to Know About Melatonin.”
How Sunlight Triggers Mitochondrial Melatonin Production
While melatonin is commonly associated with the pineal gland and nighttime sleep cycles, over 95% of your body’s melatonin is actually produced inside your mitochondria, and this process depends on your exposure to natural sunlight.6
• Near-infrared (NIR) light from the sun drives this process — NIR light, which is abundant in early morning and late afternoon sunlight, ranges from 800 to 1,000 nanometers. This range of wavelengths is invisible and has the ability to penetrate deep into your skin and activate cytochrome c oxidase in your mitochondria. This key enzyme stimulates the production of mitochondrial melatonin.7
• Mitochondrial melatonin acts as a powerful antioxidant — Unlike pineal melatonin, which follows the circadian rhythm, mitochondrial melatonin production neutralizes free radicals before they damage cellular structures, similar to how plants boost melatonin levels when exposed to environmental stressors like heat or drought.8,9
• Natural sunlight is non-negotiable — Anytime your bare skin is exposed to natural sunlight, you can be sure you’re receiving the NIR wavelengths needed to trigger melatonin production in your mitochondria. Conversely, when indoors under artificial lighting, you can be certain you’re not getting any.
• Artificial light fails to trigger this process — Artificial lighting, no matter how advanced, cannot replicate the full spectrum of natural sunlight. Most indoor lighting lacks the NIR wavelengths. Even sitting near a window offers no benefit, since low-emissivity (low-e) glass filters out the majority of NIR radiation.
To learn more about the benefits of NIR light, check out “Light Therapy Might Help Ease ‘Dry’ Form of Macular Degeneration.”
How to Optimize Your Melatonin Production Naturally
While melatonin supplementation is beneficial for certain health conditions, it’s also important to support your body’s natural melatonin production. Although melatonin has a strong safety record, long-term high doses (over 5 to 10 milligrams) may pose risks.
One concern is that melatonin helps release heavy metals like mercury from the body, which may cause damage unless properly detoxified. If taking higher doses, it’s best to follow a good detox plan and use a sauna regularly to flush out toxins. To naturally optimize your melatonin production, follow these tips:
• Get bright sunlight during the day — As explained above, sunlight plays an important role beyond regulating your circadian rhythm, which lowers melatonin during the day and increases it at night. It also delivers the wavelengths needed to activate mitochondrial melatonin production. Try to spend at least 15 minutes in the morning sun to support both sleep and cellular health.
However, it’s important to avoid high-intensity sun exposure until you’ve been off vegetable oils for about six months, as these oils significantly raise your risk of sunburn. Discover the keys to safer sun exposure in “The Role of Sun Exposure in Optimizing Your Cellular Health.”
• Limit blue light exposure at night — Blue light from phones, computers and LED lights suppresses melatonin production, making it harder to fall asleep. In the evening, use dim lighting, salt lamps, or incandescent bulbs instead of harsh LEDs. If you must use screens, wear blue-blocking glasses or install blue-light filtering software.
• Sleep in total darkness — Even small amounts of light can disrupt melatonin levels. Use blackout curtains, a sleep mask, or remove glowing electronics to create a pitch-dark sleeping environment.
• Manage stress before bed — High stress raises cortisol, which blocks norepinephrine, the hormone needed for melatonin release. Try meditation, stretching or deep breathing before bed and avoid stressful activities like work or intense discussions in the evening.
By following these natural strategies, you will help your body produce enough melatonin for restful sleep and better overall health.
Frequently Asked Questions (FAQs) About Melatonin and Muscle Health
Q: How does melatonin help prevent muscle loss?
A: Melatonin protects muscles from deterioration caused by obesity and diabetes by improving energy production, reducing oxidative stress and supporting muscle fiber regeneration.
Q: Can melatonin boost energy and endurance?
A: Yes. Melatonin helps your mitochondria work better, meaning your cells create more energy with less waste. It also shifts muscle composition to favor endurance fibers, so you stay active longer without getting tired as quickly.
Q: Does melatonin help burn fat?
A: Yes, melatonin encourages your muscles to burn fat for fuel instead of storing it. It also activates key metabolic pathways that regulate energy and prevent excess fat accumulation, making it a great tool for managing weight.
Q: What’s the best way to boost melatonin naturally?
A: To support natural melatonin production, get bright sunlight during the day, limit blue light exposure at night, sleep in total darkness and manage stress levels. These steps help regulate your circadian rhythm and optimize melatonin release.
Q: Is it safe to take high doses of melatonin?
A: Melatonin is generally safe, but very high doses (over 5 to 10 milligrams) may release stored toxins like mercury. If you’re taking higher doses, supporting detox with sauna sessions and proper nutrition helps minimize any risks.
- 1, 2 Free Radical Biology and Medicine. Volume 227, 1 February 2025, Pages 322-335
- 3 Antioxidants (Basel). 2021 Sep 17;10(9):1482
- 4 Antioxidants (Basel). 2023 Jul 27;12(8):1499
- 5 Biomedicine & Pharmacotherapy Volume 172, March 2024, 116314
- 6 Int J Mol Sci. 2021 Nov 19;22(22):12494
- 7 Biology (Basel). 2023 Jan 6;12(1):89
- 8 Curr Protein Pept Sci. 2021;22(5):413-429
- 9 CABI Agriculture and Bioscience, Volume 5, Article number: 103 (2024)
Mitochondrial Dysfunction in Neurodegenerative Disorders
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/03/31/mitochondrial-dysfunction-neurodegeneration.aspx
Analysis by Dr. Joseph Mercola March 31, 2025
STORY AT-A-GLANCE
- Mitochondrial dysfunction is a key driver of neurodegeneration, with research showing that a single resting cortical neuron requires 4.7 billion ATP molecules every second for energy
- When mitochondria lose their efficient shape, electrons escape and form reactive oxygen species (ROS), triggering cellular damage and stress that particularly affects brain cells
- Research shows 42% of adults over 55 develop dementia by age 95, with projected new cases expected to double from 514,000 in 2020 to 1 million by 2060
- Mitochondria act as cellular calcium buffers — when this function fails, calcium floods cells and triggers the mitochondrial permeability transition pore, leading to widespread neuron death
- Key mitochondrial health strategies include eliminating seed oils, optimizing carbohydrate intake, reducing environmental toxin exposure, getting proper sun exposure and boosting NAD⁺ levels through supplements
You might be startled to learn that 42% of adults over 55 develop dementia by age 95.1 Dementia is characterized by memory loss, difficulties with language and reasoning, and an overall decline in the ability to perform everyday tasks. Left unmanaged, it spirals into more severe neurodegenerative disorders that undermine independence and quality of life.
A review published in Neurotherapeutics further highlights that a single resting cortical neuron consumes 4.7 billion adenosine triphosphate (ATP) molecules every second, underscoring how energy demands in your brain are immense and ongoing.2
I see this as direct evidence of why supporting cellular powerhouses — your mitochondria — is so central to preserving cognitive health. Chronic disruptions in those energy processes impose relentless stress on nerve cells, paving the way for memory problems and other neurological setbacks.
Mitochondrial Dysfunction Is at the Root of Neurodegeneration
The Neurotherapeutics review3 examined how different forms of disrupted energy processes in brain cells set the stage for progressive neurological disease. The researchers looked at various research findings that link faulty mitochondrial function to disorders affecting cognition, motor control and other higher-level tasks.
Their central goal was to pinpoint how malfunctioning mitochondria trigger the chain reactions seen in conditions such as Alzheimer’s disease, Parkinson’s disease and multiple other neurological syndromes.
• Evidence reveal how mitochondrial dysfunction drives brain changes — Investigators in this review did not limit their analysis to a specific group of patients. Instead, they consolidated evidence from a broad range of laboratory experiments and clinical observations targeting aging populations, individuals with rare mitochondrial disorders and those carrying known genetic mutations that alter mitochondrial function.
By weaving these areas together, the authors hoped to create a clearer picture of how compromised energy production leads to characteristic brain changes.
• Even small changes lead to significant damage — One of the paper’s most striking observations is how tiny structural shifts inside the mitochondria snowball into large-scale damage.4 When these organelles lose their efficient shape, electrons slip out of the normal energy pathway and team up with oxygen to form corrosive molecules called reactive oxygen species (ROS).
That surge in ROS sets off a cascade of biochemical stressors throughout brain cells, including direct attacks on important proteins and fats.
• The mitochondrion’s structure has a substantial role in neurofunction — As the authors state, “Excessive ROS production damages a variety of cellular components including proteins, lipids and DNA.”5 In short, the mitochondrion’s shape and integrity hold more power over neurofunction than many imagine.
Apart from the physical shape, researchers also honed in on the role of calcium balance. Healthy mitochondria function as a buffer by absorbing and releasing calcium ions to keep cells in balance.6
• The mitochondrial permeability transition pore leads to cell death — Once there’s a glitch, calcium floods the cell, and an emergency process called the mitochondrial permeability transition pore springs open.
The paper emphasizes that an uncontrolled opening of this pore triggers a wave of cell death, especially in your brain’s vulnerable neurons, where energy demands are already sky-high. It’s like watching a dam collapse because the main floodgate jammed.
Another intriguing angle involves how failing mitochondria disturb normal protein cleanup processes in the cell.7 The authors detail a scenario in which damaged mitochondria release proinflammatory signals, slowing down or outright blocking autophagy, the system cells use to clear out junk.
This slowdown contributes to the buildup of toxic plaques and misfolded proteins that characterize several neurodegenerative conditions. In practical terms, it means that your body’s usual housekeeping can’t keep up with the mess, and your brain is the unfortunate casualty.
Mitochondrial Dysfunction Tied to Parkinson’s, Alzheimer’s and Other Disorders
Throughout the review, there’s a clear focus on how each neurodegenerative disease taps into similar mitochondrial weaknesses.8 For instance, while Parkinson’s disease involves a breakdown in dopamine-producing neurons, and Alzheimer’s centers on beta-amyloid plaques, both conditions involve disruption of electron transport inside the mitochondria.
• One targeted intervention can influence many conditions — By comparing these processes side by side, the authors illustrate how one targeted intervention has benefits across multiple disorders. It’s a refreshing perspective that encourages looking beyond siloed research for cures or therapies. The researchers also address how the paper’s findings reflect on the broader population and our understanding of age-related memory and motor decline.9
• The connection between normal aging and mitochondrial collapse — They connect the dots between normal aging, which often features mild mitochondrial dysfunction, and more severe mitochondrial collapse seen in advanced disease states.
That means many people could be slipping down this slope long before typical symptoms even appear. According to the paper, identifying biomarkers of mitochondrial damage helps clinicians detect disease pathways early enough for effective interventions.
• ROS production modifies cellular signals — The authors also describe an intricate sequence of oxidative reactions that damage DNA, disrupt telomeres — the protective caps at the ends of chromosomes — and even alter the way genes are expressed.10
The review suggests that once ROS production speeds up, it doesn’t just drain energy — it also modifies cellular signals that keep neurons alive and functional. These modifications eventually tip cells into an energy crisis they cannot recover from, leading to unstoppable cell loss.
• Antioxidants help stabilize electron transport — Additionally, there’s discussion of how certain antioxidant strategies might stabilize electron transport by shielding the delicate proteins and lipids inside mitochondria.11
Some early-phase clinical trials, the paper notes, show promise in using compounds that block the worst of the oxidative assaults. While these lines of research are still evolving, they shine a bright light on the possibility of halting mitochondrial problems before serious neurological damage becomes entrenched.
Overall, this review underscores that protecting your cell’s power plants is a direct route to preserving brain function.12 By mapping the many crossroads where mitochondrial decline intersects with cognitive decline, researchers open doors to therapies that restore healthy energy production and help you maintain sharper memory, better coordination and greater resilience in the face of escalating demands on your brain.
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The Growing Alzheimer’s Risk in Aging Populations
Understanding mitochondrial dysfunction’s role in neurodegeneration becomes urgent in the face of rising dementia cases. A study published in Nature Medicine13 tackled a massive data set on dementia, focusing on which groups are diagnosed most often, how early in life it occurs and how these trends shift over time.
Rather than exploring microscopic changes in the brain, this work looked closely at how social, genetic and age-related elements determine whether someone develops cognitive decline.
• Identifying the role of APOE ε4 in dementia development — Investigators pulled from a community-based study of thousands of participants, each free of dementia at the start, but varying in age, background and genetic traits.14 Their top priority was to measure how a person’s chances of developing dementia changed when factors such as sex, race and a specific genetic marker known as APOE ε4 came into play.
• Differences were seen between genders — By layering in long-term follow-up data and population statistics, they aimed to predict how many new dementia diagnoses would appear each year over the next several decades. A closer look revealed some dramatic differences between men and women.15
The paper found that women’s overall risk for dementia was higher than men’s when viewed across a lifetime, even though men often faced a greater likelihood of dying from other causes before cognitive problems fully manifested.
• Hormonal factors amplify the toll — In simpler language, men did not always reach the ages at which dementia most commonly appears. This gap sparked questions about how unique hormonal factors and longer lifespans amplify the toll on older women.
The same research found that Black adults were diagnosed with dementia at higher rates than White adults.16 This trend kicked in earlier, hinting that certain structural or social conditions accelerate the onset of memory loss.
• Certain factors affect dementia development — The paper noted that higher burdens of vascular complications, challenges with health care access and long-standing inequities could be part of the reason more Black adults developed dementia at younger ages. Investigators highlighted yet another twist: the APOE ε4 gene variant.17
This genetic factor often signals a heightened risk of Alzheimer’s disease, which falls under the broader dementia umbrella. Individuals carrying one copy showed a higher likelihood of facing cognitive problems, and those carrying two copies saw their odds jump even further.
• Dementia cases can rise to 1 million by 2060 — Looking ahead, the paper revealed a stark projection: around 514,000 new dementia cases occurred in 2020, but that total is expected to hit roughly 1 million by 2060.18 This doubling in newly diagnosed individuals points to significant population aging, where large segments of people are moving into the higher-risk age brackets at once.
Overall, the Nature Medicine paper19 suggests that the growing number of new dementia cases will not slow unless older adults gain more consistent access to early detection, better lifestyle options and interventions that protect their cognitive abilities — including optimizing your mitochondrial function.
How to Support Mitochondrial Health
You deserve straightforward ways to tackle an actual cause of neurodegeneration: a drop in cellular energy that wears down your nerve cells. I believe that if you support your mitochondria properly, you strengthen your brain and spare yourself from many issues that come with mitochondrial dysfunction. Below are five steps that focus on restoring mitochondrial health to boost your cellular power:
1. Eliminate processed foods and seed oils — I recommend shifting your diet away from seed oils like corn, soybean, safflower or canola. These oils contain linoleic acid (LA), a mitochondrial poison that compromises your cellular energy production. Aim to center your meals around wholesome foods such as fresh vegetables, grass fed butter or tallow, and clean collagen-rich proteins.
If you’re eating out, confirm what kind of oil they use in the kitchen — and opt out if it’s seed oil. This step helps protect your mitochondria from damage that accumulates over time, ultimately preserving your brain’s vitality.
2. Optimize your carbohydrate intake — Certain carbs are essential for steady energy output, especially keeping your neurons fueled. If you have a compromised gut, it’s important to start with easier-to-digest options, like white rice or slowly sipping dextrose water.
Over time, work in whole fruits and other nutrient-dense carbs. If you’re active, your needs are higher, so tailoring your intake ensures you’re not draining your mitochondria by consuming a low-carb diet.
3. Reduce exposure to environmental toxins — Your cells get bombarded by synthetic chemicals daily. Exposure to endocrine-disrupting chemicals (EDCs) in plastic, estrogen and pervasive electromagnetic fields (EMFs) impairs your cells’ ability to generate energy efficiently. As these pollutants build up, the mitochondria lose efficiency.
That’s why I recommend being proactive about reducing your exposure to environmental toxins. Consider household products made from natural materials and glass storage for leftovers. Sleeping in an EMF-free environment is also important, as it gives your cells a breather while your body recharges overnight. All of this lowers the stress your body must handle.
4. Get proper sun exposure — Daily sun exposure is important as it promotes cellular energy production by stimulating mitochondrial melatonin, offering powerful antioxidant protection. Avoid direct sunlight during peak hours (from 10 a.m. to 4 p.m. in most U.S. regions) until you’ve eliminated seed oils from your diet for at least six months, because accumulated LA in your tissues make you sunburn more easily.
5. Boost NAD+ Levels — Take niacinamide (50 milligrams three times daily) to increase NAD+ production, which helps your mitochondria generate more energy. NAD+ enables proper cell death signaling and supports your immune system’s ability to identify and remove damaged cells.
Frequently Asked Questions (FAQs) About Mitochondrial Dysfunction
Q: Why are mitochondria so important for brain health?
A: Mitochondria are the brain’s energy powerhouses, with a single resting cortical neuron using 4.7 billion ATP molecules every second. Mitochondrial dysfunction leads to energy deficits, oxidative stress, and neuron damage — all contributing to neurodegenerative diseases.
Q: How does mitochondrial dysfunction contribute to neurodegenerative disorders like Alzheimer’s and Parkinson’s?
A: Damaged mitochondria release reactive oxygen species (ROS) and disrupt calcium balance, triggering cell death and blocking cellular cleanup systems. This process causes toxic buildup and accelerates conditions such as Alzheimer’s and Parkinson’s.
Q: How widespread is dementia, and what are future projections?
A: Currently, 42% of adults over 55 develop dementia by age 95. New dementia cases are projected to double from 514,000 in 2020 to around 1 million by 2060 due to an aging population and genetic risk factors like the APOE ε4 gene variant.
Q: What lifestyle factors help protect mitochondrial function and reduce neurodegeneration risk?
A: Key strategies include eliminating seed oils, optimizing healthy carbohydrates, minimizing exposure to environmental toxins, getting proper sun exposure, and boosting NAD+ levels through niacinamide supplementation.
Q: What early signs and interventions are emphasized in preventing cognitive decline?
A: Detecting mitochondrial damage early through biomarkers, along with antioxidant therapies and targeted lifestyle changes, can help slow or prevent the onset of neurodegenerative diseases and age-related memory decline.
- 1, 13, 14, 15, 16, 17, 18, 19 Nature Medicine January 13, 2025
- 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 Neurotherapeutics December 19, 2023;21(1):e00292
Filling the Tank — Restoring Cellular Energy (Part 2)
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/03/22/restoring-cellular-energy-part-2.aspx
Analysis by Dr. Joseph Mercola March 22, 2025
STORY AT-A-GLANCE
- A body without cellular energy is like a car without fuel. Providing your body with the right nutrition, exercise, sleep, and sunlight exposure is essential to maintaining and replenishing these vital energy reserves
- Exercise, particularly interval training and resistance exercises, stimulates mitochondrial biogenesis and enhances your body’s capacity to generate energy and improve metabolic health
- Quality sleep enables cellular repair. This allows your mitochondria to restore and regenerate through processes like mitophagy and aligns your body’s circadian rhythms
- Sunlight exposure directly fuels mitochondria by converting red and near-infrared light into electrons. This supports ATP production and synchronizes your body’s internal energy systems
- To safely benefit from sun exposure, eliminate vegetable oils from your diet first. They contain linoleic acid that accumulates in your skin and increases your risk of UV-induced oxidative stress and sunburn
A body without energy is like a car without gas. No matter how well its components are maintained, it cannot run without fuel to power its engine. Everyday factors like eating a poor, ultraprocessed diet, exposure to environmental toxins and the relentless demands of modern life drain your body’s reserves, leaving you running on empty.
When cellular energy is depleted, even a body that appears healthy from the outside will struggle to sustain its internal processes — cells lose the ability to repair themselves, tissues break down and chronic diseases take hold. Yet, modern medicine often focuses on masking symptoms of this cellular energy deficit rather than addressing the underlying cause.
Solving this energy crisis requires more than surface-level solutions. It needs a deeper, deliberate strategic approach that tackles the root causes of mitochondrial dysfunction. In Part 1, you learned how to nourish yourself with the right foods. Here, in Part 2, I’ll review some of the key lifestyle strategies that revitalize energy production and restore your innate ability to heal and thrive.
How Exercise Catalyzes Energy Production
The next pillar of optimal energy production is physical activity, one of the most powerful stimulators of mitochondrial biogenesis, the process by which cells create new mitochondria.
• Exercise triggers mitochondrial adaptation — During exercise, muscles consume large amounts of ATP (energy) to fuel their contractions, creating a temporary energy deficit.1 This prompts cellular responses to enhance the mitochondria’s capacity to generate energy, as well as increase the number of mitochondria within the cells, to meet the muscles’ demands more effectively.
• The type and intensity of exercise matters — Not all forms of exercise provide the same mitochondrial benefits. Strategic forms of activity, such as high-intensity interval training (HIIT), resistance exercises, and moderate-intensity movement, offer unique benefits for mitochondrial health.
Revitalizing Mitochondrial Health Through HIIT
High-intensity interval training (HIIT) is a form of exercise that alternates between periods of high-intensity effort and low-intensity recovery. This method challenges your cardiovascular and muscular systems by repeatedly pushing your body to exert maximum effort for short bursts, followed by periods of active rest or lighter activity.
• Interval walking training (IWT) is a simple yet powerful form of interval training — IWT alternates between three minutes of relaxed walking and three minutes of brisk walking over a 30-minute session. This method combines the simplicity of walking with the metabolic benefits of interval activity, making it an effective and accessible exercise option for people of all fitness levels.2
• IWT is easy to implement — Nose Hiroshi, the creator of IWT, outlines the following steps to incorporate this method into your routine:3
1.Begin with proper stretching to prepare your muscles.
2.Start walking with small strides, maintaining a pace that allows you to comfortably hold a conversation.
3.Increase intensity by taking larger strides, ensuring your heels contact the ground first, followed by your toes.
4.Bend your arms at a right angle and swing them naturally, using this motion to encourage larger, more powerful strides. Aim for a pace that lightly engages your calf muscles.
5.Alternate between three minutes of slower, relaxed walking and three minutes of faster, more intense walking.
6.Gradually work toward a goal of 60 minutes of brisk walking per week, spread over multiple sessions to make it manageable and sustainable.
•A gradual approach prevents overexertion and maximizes benefits — For beginners, starting with one or two IWT sessions per week, gradually increasing duration and frequency, offers a manageable way to improve mitochondrial function without overtaxing your body.
The simplicity and effectiveness of IWT make it a foundational exercise for individuals looking to restore energy levels and improve overall health. To learn more about IWT, read “Interval Walking Training — Going Beyond Step Count.”
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Can Resistance Training Boost Metabolic Health?
Resistance training further enhances mitochondrial health by targeting large muscle groups and creating localized energy demands. Exercises like squats, deadlifts, and rows not only strengthen muscles but also stimulate mitochondrial biogenesis, the process by which cells create new mitochondria to produce more energy.
• Resistance training stimulates mitochondrial biogenesis — Engaging large muscle groups activates key regulatory proteins, such as PGC-1α, which signals cells to produce more mitochondria, and TFAM, which helps maintain and repair mitochondrial DNA.4
• Resistance training also builds lean muscle mass — This boosts your resting metabolic rate and supports long-term energy production. It improves insulin sensitivity as well, enhancing the ability of your muscles to use glucose and fats as fuel.5,6,7
• Balance training duration to avoid diminishing returns — To maximize the benefits of resistance training without risking overtraining, research shows the ideal duration is 30 to 60 minutes per week. Exceeding 130 minutes of weekly resistance training has been shown to negate longevity benefits, so moderation is key.8
To learn more about the optimal amount of exercise for health and longevity, check out “Nailing the Sweet Spots for Exercise Volume.”
Balancing Your Exercise Routine for Optimal Energy
Other studies support the importance of balancing exercise intensity. For example, a study published in Cell Metabolism9 observed that progressively increasing exercise intensity improved performance and mitochondrial adaptations up to a point. However, excessive training resulted in a 40% reduction in mitochondrial respiration. This decline was accompanied by impaired glucose regulation and insulin secretion, key markers of metabolic dysfunction.
• Overtraining reduces mitochondrial efficiency — While excessive training causes your body to compensate by increasing the number of mitochondria, this doesn’t stop their overall function from declining. This is why it’s important to balance how hard and how often you exercise, allowing time for recovery to keep your mitochondria healthy.
• Moderate-intensity activities support energy without drawbacks — Moderate-intensity activities, such as walking and recreational cycling, are excellent options for those with poor mitochondrial health or limited energy reserves — and do not diminish longevity benefits beyond a certain point. Moreover, practices like restorative yoga, gentle stretching or even mindful relaxation support your body’s ability to repair and regenerate.
• A well-rounded exercise plan enhances both physical and cellular health — By aligning physical activity with your individual energy levels and prioritizing recovery, you’ll be able to achieve a sustainable and effective approach to restoring cellular energy and building resilience.
The Importance of Sleep for Cellular Repair
No discussion of cellular energy restoration would be complete without addressing sleep. Sleep is a fundamental process for mitochondrial repair and optimal energy production.
• Deep sleep supports mitochondrial maintenance — During deep sleep, your body enters a state where energy demand decreases, allowing cells to focus on restorative processes. This includes repairing mitochondrial membranes and removing damaged components through mitophagy, a process that ensures energy production remains efficient.10
• Sleep drives the production of essential molecules — These include melatonin and growth hormone, which not only regulate mitochondrial function but also help neutralize oxidative stress, protecting mitochondria from further damage. The circadian rhythms that govern sleep also play a pivotal role in cellular energy regulation.11
• Circadian rhythms synchronize energy regulation — At night, these rhythms align mitochondrial activity with your body’s lowered energy demands, enhancing their efficiency and allowing for the replenishment of energy reserves. This synchronization is vital for maintaining a balance between energy production and repair, ensuring that mitochondria are primed to meet your body’s demands upon waking.
Practical Strategies to Improve Your Sleep Hygiene
Improving sleep quality involves a proactive approach that addresses environmental, behavioral, and nutritional factors to support restorative rest and mitochondrial repair.
• Minimize blue light exposure in the evening — This is one of the most effective strategies to get better sleep. Using screen filters, wearing blue-light-blocking glasses, or turning off electronic devices at least an hour before bed restores natural melatonin levels, enabling your body to transition into a repair-focused state.12
• Optimize your sleep environment — A dark, quiet, and cool bedroom promotes deeper, more restorative sleep by reducing external disturbances. Blackout curtains, white noise machines, and adjustable thermostats are practical tools that enhance your sleep environment. Maintaining a room temperature between 60 and 68 degrees Fahrenheit supports your body’s natural drop in core temperature, which facilitates the transition into sleep.
• Minimizing exposure to electromagnetic fields (EMFs) — EMFs from devices such as cell phones, Wi-Fi routers, and other electronics interfere with melatonin production and disrupt your circadian rhythm. Unplugging devices, turning off Wi-Fi at night, and keeping electronics out of the bedroom significantly reduce EMF exposure.
• Establish a consistent bedtime routine — Going to bed and waking up at the same time every day reinforces your body’s circadian rhythm, optimizing the timing of repair processes. Incorporating relaxing pre-sleep activities, such as taking a warm bath or practicing mindfulness, signals your body to prepare for sleep.13
• Exercise at the right time — Engaging in physical activity earlier in the day improves your sleep quality by aligning your circadian rhythm and regulating your hormone levels.14 Morning or early afternoon exercise is ideal, as it avoids the stimulating effects that interfere with relaxation in the evening.
• Time your meals appropriately — It’s wise to avoid heavy meals close to bedtime to avoid disruptions to digestion and blood sugar levels.15
• Use nutritional support wisely — Magnesium is a key component for sleep due to its ability to promote relaxation.16 I recommend magnesium glycinate and malate, especially in delayed time-release formats, as it prevents the magnesium from causing loose stools.
To find the right dosage, start with 400 milligrams to 500 milligrams and gradually increase the amount until you notice mildly loose stools. That’s your maximum dose. Once you’ve determined this threshold dose, you can transition to magnesium threonate if you wish.
• Melatonin helps if your circadian rhythm is already disrupted — Low doses, taken 30 to 60 minutes before bedtime, aid in resetting your body’s internal clock. However, melatonin use should be viewed as a short-term solution while lifestyle adjustments are implemented to address the root causes of poor sleep. Overreliance on supplements will diminish your body’s natural production over time.
Get more tips to improve your sleep in “Sleep — Why You Need It and 50 Ways to Improve It.”
What’s the Link Between Sunlight, Circadian Health, and Your Cells?
Sunlight is one of the most powerful and underappreciated tools for optimizing cellular health. Just as plants harness sunlight for photosynthesis, your body transforms sunlight into energy at the cellular level.
• Mitochondria harness sunlight for energy production — When red and near-infrared light from the sun touches your skin, your mitochondria absorb these wavelengths, converting them into electrons. These electrons are fed directly into the electron transport chain, enabling the production of ATP. Unlike energy derived from food, which undergoes complex metabolic pathways, sunlight offers a direct and efficient way to fuel mitochondrial function.
• Sunlight light boosts mitochondrial antioxidants — Near-infrared light activates cytochrome c oxidase in your mitochondria. This key enzyme stimulates the production of mitochondrial melatonin. Unlike pineal melatonin, which regulates your sleep-wake cycle, mitochondrial melatonin functions as a powerful antioxidant within the cells.17
• Morning sunlight synchronizes your circadian rhythm — Exposure to early morning sunlight helps regulate your body’s internal clock, synchronizing your circadian rhythm with the natural cycles of day and night. To support this process, try spending time outdoors as soon as you wake up, whether walking or sitting in direct sunlight. Midday sunlight is equally important, as it provides ultraviolet B (UVB) rays necessary for vitamin D synthesis.
To learn more about the vital role of sunlight in energy production and cellular function, read “The Role of Sun Exposure in Optimizing Your Cellular Health.”
Unlocking the Power of Sunlight — Six Ways to Boost Your Sun Exposure
As important as sun exposure is, before you spend time in the sun, consider your diet. If it’s currently high in linoleic acid (LA), your approach to high-intensity sun exposure requires careful planning. LA accumulates in your skin, making it highly susceptible to oxidative damage when exposed to UV light, putting you at higher risk of sunburn.
1. Eliminate vegetable oils before increasing sun exposure — To fully benefit from sunlight while avoiding its harmful effects, your first priority should be to eliminate vegetable oils and ultraprocessed foods from your diet. It takes about six months for your body to sufficiently clear some of these harmful fats from your tissues.
2. Adjust sun exposure while detoxing from LA — Avoid intense sun exposure around peak hours, typically one hour before and after solar noon. In most of the U.S. during summer, this means avoiding direct sunlight from 11 a.m. to 3 p.m. during Daylight Saving Time or from 10 a.m. to 2 p.m. during Standard Time.
While you won’t get the full spectrum of sunlight’s health benefits outside of these times, it will allow you to safely ease into exposure while your skin detoxes. Once your tissues are free from the damaging effects of vegetable oils, your skin will be better equipped to handle direct sunlight without the toxic byproducts that result from LA oxidation.
3. Once your body is ready, optimize sun exposure — Aim to spend time outdoors around solar noon — approximately 12 p.m. or 1 p.m. during Daylight Saving Time. This is when ultraviolet (UV) and near-infrared light are at their peak, providing the optimal conditions for vitamin D synthesis and mitochondrial energy production.
4. Ease into sunlight gradually — Begin with 10 to 15 minutes of exposure, depending on your skin tone, and gradually increase your time as your skin adapts. To maximize the benefits, expose as much skin as possible without sunscreen, but avoid overexposure because it increases your risk of sunburn or oxidative stress. Cover up with protective clothing as soon as your skin turns the slightest shade of pink.
5. Consider your skin tone — For individuals with darker skin tones, there is no specific color change equivalent to the “light shade of pink” that indicates sufficient sun exposure for vitamin D production. This is because melanin, the pigment that gives skin its color, acts as a natural sunscreen and affects vitamin D synthesis differently in darker skin.
Instead of looking for a color change, people with darker skin should focus on controlled sun exposure times. Most studies recommend 25 to 40 minutes of daily sunlight exposure for brown and black skin.18
6. Plan your day around this invaluable practice — Whether it’s a lunch break outdoors, a walk during solar noon or a brief pause to soak up the sun’s energy. By aligning your habits with the natural rhythm of sunlight, you unlock its profound potential to support your cellular health and overall vitality.
The Path Forward
Your cells are equipped with an extraordinary ability to repair, regenerate, and thrive, but this remarkable potential depends on keeping your cellular “fuel tank” full. Without adequate energy, your systems will falter, leaving you vulnerable to disease and chronic dysfunction. The key to optimizing your cellular energy lies in replenishing your mitochondria with the right inputs while removing the obstacles that drain their capacity.
• Eliminating barriers unlocks true healing — When you resolve the underlying disruptions to mitochondrial function, you unlock your body’s ability to heal from virtually any disease, so you no longer need to rely on temporary fixes from modern medicine that only mask the underlying problem. Instead, you build the foundation for health that is resilient, enduring, and rooted in the natural design of your body.
• Cellular energy is a vital yet overlooked link — Modern medicine has ignored the importance of cellular health for far too long. Refueling your cells with the nutrients, lifestyle habits, and restorative practices they need isn’t just a novel approach — it is the only approach that delivers real, lasting results.
• Revolutionizing health through energy-based medicine — Placing cellular energy at the core of every diagnosis and treatment plan redefines the medical paradigm, fundamentally transforming how we prevent and treat diseases. This is a revolution in health and a return to what medicine was always meant to be — a system that supports your body’s ability to restore itself, not suppress it.
The path forward is clear — it begins with cellular energy, the true foundation of lasting wellness.
Frequently Asked Questions (FAQs) About Restoring Cellular Health
Q: Why is cellular energy important for overall health?
A: Your cells need energy to repair themselves, maintain function, and prevent disease. When energy levels drop, your body struggles to heal, leading to fatigue, muscle loss, metabolic issues, and chronic illness.
Q: How does exercise improve mitochondrial function?
A: Exercise stimulates mitochondrial biogenesis, increasing the number and efficiency of mitochondria. High-intensity interval training (HIIT) and resistance training are especially effective at boosting energy production and metabolic health.
Q: What role does sleep play in energy production?
A: Deep sleep is when your body repairs mitochondria, removes damaged cells, and restores energy reserves. Poor sleep disrupts this process, leading to fatigue, inflammation, and lower cellular function.
Q: How does sunlight impact cellular energy?
A: Sunlight stimulates mitochondrial melatonin production, reduces oxidative stress, and helps regulate your circadian rhythm. Morning and midday sun exposure optimizes vitamin D and energy production.
Q: What are the best ways to improve energy levels naturally?
A: Support your mitochondria by eating whole foods, exercising regularly, prioritizing quality sleep, reducing stress, and getting daily sunlight. Avoiding ultraprocessed foods, vegetable oils and environmental toxins also helps maintain optimal cellular function.
- 1 Nature Metabolism Volume 2, Pages 817–828 (2020)
- 2 Appl Physiol Nutr Metab. 2024 Jul 1;49(7):1002-1007
- 3 Youtube, NHK World-Japan, New Findings on Walking and Running – Medical Frontiers
- 4 The Journal of Physiology, February 2021; Volume 599, Issue 3: Pages 803-817
- 5 Sports Med 52, 463–479 (2022)
- 6 Eur J Clin Nutr. 2015 Jul;69(7):831-6
- 7 Journal of Exercise Science & Fitness Volume 19, Issue 4, October 2021, Pages 241-251
- 8 Missouri Medicine March-April 2023; 120(2): 155–162
- 9 Cell Metabolism. Volume 33, Issue 5, 4 May 2021, Pages 957-970.e6
- 10, 11 Antioxidants (Basel). 2023 Mar 9;12(3):674
- 12 Sleep Adv. 2020 Jun 4;1(1):zpaa002
- 13, 15 Cureus. 2024 Jun 3;16(6):e61568
- 14 Biomolecules. 2024 Nov 7;14(11):1418
- 16 Biol Trace Elem Res. 2023 Jan;201(1):121-128
- 17 Biology (Basel). 2023 Jan 6;12(1):89, Role of Non-Visible Near Infrared (NIR) Radiation on Melatonin Synthesis
- 18 Nutrients. 2018 Apr 7;10(4):457
Mitochondrial Dysfunction Sparks Inflammation and Cancer Risk
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/03/19/mitochondrial-dysfunction.aspx
Analysis by Dr. Joseph Mercola March 19, 2025
STORY AT-A-GLANCE
- Suppression of mitochondrial ATP production prevents apoptosis and activates the NLRP3 inflammasome, a key player in inflammation and disease
- Inhibitors of oxidative phosphorylation (OXPHOS) lead to changes in mitochondrial cristae structure and retention of cytochrome c, which is necessary for NLRP3 activation but not sufficient on its own
- Activation of the NLRP3 inflammasome requires two signals, one of which is mitochondrial, highlighting the complexity of its regulation
- Diverse NLRP3 activators share the ability to suppress apoptosis, allowing damaged cells to survive and contributing to chronic inflammation and cancer
- Mitochondrial dysfunction is closely linked to inflammation and various diseases, emphasizing the importance of understanding these mechanisms for optimal health
Chronic inflammation and cancer are health challenges that affect millions of individuals worldwide. Inflammation is your body’s natural response to injury or infection, characterized by redness, swelling and pain. However, when inflammation becomes persistent, it leads to tissue damage and contributes to the development of various diseases, including cancer.
Cancer itself is marked by the uncontrolled growth and spread of abnormal cells, which invade surrounding tissues and form harmful tumors. If left untreated, these conditions significantly impair quality of life and increase mortality rates. Mitochondria, often referred to as the powerhouses of the cell, play a key role in producing adenosine triphosphate (ATP), the energy currency essential for numerous cellular functions.
When mitochondrial function is compromised, ATP production decreases, leading to cellular energy deficits. This reduction in energy impairs the cell’s ability to regulate normal processes, fostering an environment ripe for chronic inflammation.
According to research published in Immunity,1 impaired mitochondrial function directly activates the NOD-like receptor protein 3 (NLRP3) inflammasome, a key component in the inflammatory response. This activation not only sustains inflammation but also creates conditions that promote cancer development by enabling cancer cells to thrive and evade your immune system.
Mitochondrial Function Is Intricately Involved in Inflammation and Cancer
The impact of mitochondrial dysfunction on inflammation and cancer is significant. Studies show that approximately 20% of all cancers are linked to chronic inflammation, highlighting the strong connection between these conditions.2 Additionally, individuals with mitochondrial disorders are at a higher risk of developing inflammatory diseases compared to the general population.3
• Millions of Americans are affected by mitochondrial dysfunction — In the U.S. alone, chronic inflammatory conditions affect close to 125 million adults,4 while cancer remains the second leading cause of death, accounting for more than 608,000 fatalities each year.5 Moreover, research indicates that mitochondrial dysfunction contributes to the resistance of cancer cells to conventional therapies, making treatment more challenging.6
• A call to action for better treatment for mitochondrial health — The statistics underscore the urgent need to address mitochondrial health as a strategy to combat both inflammation and cancer effectively.
Beyond their direct effects, chronic inflammation and cancer driven by mitochondrial dysfunction leads to a cascade of additional health problems. Persistent inflammation is associated with cardiovascular diseases, diabetes and neurodegenerative disorders, further compounding the burden on affected individuals.
• Cancer stems largely from mitochondrial dysfunction — Cancer progression often results in debilitating symptoms such as pain, fatigue and loss of organ function, which drastically reduces life expectancy and quality of life.
Understanding the role of mitochondrial dysfunction in driving inflammation and cancer not only illuminates therapeutic targets but also emphasizes the importance of maintaining mitochondrial health to prevent a wide array of serious health issues.
• Mitochondrial dysfunction is a key player in the development of NLRP3-related conditions — When mitochondria fail to produce adequate ATP, it sets off a cascade of cellular stress signals.
These signals activate the NLRP3 inflammasome, a protein complex that plays a significant role in the body’s inflammatory response.7 The activation of this inflammasome is linked to various diseases, including chronic inflammation and cancer, as it leads to uncontrolled cell death and tissue damage.
Study Reveals How Mitochondrial Dysfunction Fuels Inflammation and Cancer
A recent study investigated the intricate relationship between mitochondrial function and the activation of the NLRP3 inflammasome. The research focused on understanding how the inhibition of oxidative phosphorylation (OXPHOS), the process by which mitochondria produce ATP, affects cell death and inflammation.
The study employed various cell types, including myeloid cells, primary murine microglia, human monocyte-derived macrophages, HCT116 and HeLa cells, as well as conducted in vivo experiments using Xenopus laevis tadpoles.8
• The NLRP3 inflammasome negatively impacts mitochondrial health — The population studied encompassed a diverse range of cells to mimic different physiological conditions. The findings revealed that activators of NLRP3 significantly hinder mitochondrial ATP production, which in turn suppresses apoptosis, the process of programmed cell death.
This suppression allows damaged cells to survive longer than they should, contributing to inflammation and leading to cancer development. The study demonstrated that when OXPHOS is inhibited, mitochondrial cristae — the inner folds of mitochondria — undergo structural changes that trap cytochrome c, a molecule essential for apoptosis.9
• Other factors that diminish apoptosis — The research also showed that various NLRP3 activators, such as nigericin, imiquimod and extracellular ATP, inhibit apoptosis not by activating the inflammasome directly, but through their disruptive effects on mitochondrial function. These compounds cause the closure of crista junctions, preventing cytochrome c from being released into the cytoplasm, which is a necessary step for apoptosis to proceed.
• The impact of viral infections on mitochondrial function and apoptosis — It was observed that infections like SARS-CoV-2 could strongly suppress apoptosis by inhibiting the cleavage of caspase-3, an enzyme involved in the execution of apoptosis. This suppression not only hinders the removal of infected cells but also facilitates the activation of the NLRP3 inflammasome, thereby promoting an inflammatory response.10
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Mitochondrial Dysfunction Is at the Root of Most Chronic Disease
Biologically, the mechanism at play involves the inhibition of mitochondrial ATP production by NLRP3 activators. When OXPHOS is blocked, mitochondria cannot produce sufficient ATP, leading to the rearrangement of cristae and retention of cytochrome c within the mitochondria. This retention prevents apoptosis, allowing damaged cells to survive and multiply unchecked.
• The process of NLRP3 signaling and activation — The suppression of ATP production provides a necessary signal for the activation of NLRP3. However, full activation of NLRP3 requires a second signal, highlighting the complexity of the inflammasome’s regulation.11
The study also compared the effects of different NLRP3 activators and OXPHOS inhibitors, revealing that while all these agents suppress apoptosis, only certain ones could activate NLRP3 without an additional signal.
• A way to control mitochondrial processes to facilitate healing — This comparison highlights the intricate relationship between mitochondrial function and inflammasome activation, suggesting that modulating mitochondrial processes could be an effective strategy for managing inflammation and reducing cancer risk.12
The research provides compelling evidence that mitochondrial dysfunction, specifically through the inhibition of OXPHOS, plays a pivotal role in suppressing apoptosis and activating the NLRP3 inflammasome.
This dual action not only fosters a proinflammatory environment but also allows for the survival of malignant cells, thereby linking reduced mitochondrial function to the progression of inflammation and cancer.13 As noted on Georgi Dinkov’s blog, the study demonstrates that mitochondrial dysfunction is a key player in both cancer and inflammation:14
“Yet another study, which demonstrates the inseparable link between metabolism and ‘structural’ problems such as cellular integrity and lifecycle (e.g. apoptosis), as well as mysterious processes of systemic inflammation, often occurring without any cause that medicine can identify.
Both of these processes are highly visible in cancer — i.e., lack of apoptosis in ‘cancer’ cells despite their wrecked genome and metabolic dysfunction, as well as their highly inflamed nature that ‘recruits’ nearby cells to the ‘cancer’ process through the cytokines the ‘cancer’ cells produce and releases in the blood.
In other words, all that takes for systemic inflammation and even cancer (i.e., lack of apoptosis in damaged cells) to form is reduced mitochondrial function, resulting in a prolonged drop of ATP levels.
Thus, chronic stress, inflammatory diet (PUFA anyone?), endocrine disruptors, and the ‘modern’ life characterized by never-ending soul-crushing routines are all direct causes of all our ailments as the one thing all those pathological processes have in common is their profoundly suppressive effects on mitochondria/OXPHOS.
Conversely, simply restoring/improving mitochondrial function may be enough to ameliorate/cure virtually all chronic diseases known to medicine.”
How to Address Mitochondrial Dysfunction and Reduce Inflammation
Your mitochondria power every cell in your body. When they don’t work properly, inflammation rises and damaged cells multiply instead of dying off naturally. Here’s how to support your mitochondrial function and restore cellular energy:
1. Eliminate processed foods and vegetable oils — The modern diet is rife with processed foods and vegetable oils rich in linoleic acid (LA) that damage your gut microbiome and promote harmful bacteria.
LA is a mitochondrial poison that compromises your cellular energy production. In addition to processed foods, avoid nuts and seeds as well to reduce LA intake. It’s also advisable to avoid dining out, since most restaurants use vegetable oils in their cooking, sauces and dressings.
Additionally, limit your consumption of chicken and pork, which are typically high in LA. Replace processed foods with whole, unprocessed foods and healthy fats such as grass fed butter, tallow and ghee. It’s wise to keep your LA intake below 5 grams from all sources. If you can get it below 2 grams, that’s even better. To help track your LA intake, enter all your daily meals into an online nutrition tracker.
2. Optimize carbohydrate intake — Carbohydrates play an important role in supporting mitochondrial function since glucose is the preferred fuel for energy production at the cellular level. Tailor your carbohydrate consumption to support cellular energy by aiming for at least 250 grams of targeted carbohydrates daily for most adults. Individuals with higher activity levels typically require more.
Introduce carbohydrates gradually to allow your gut to adapt, thereby minimizing digestive issues and endotoxin levels. Begin with white rice and whole fruits to nourish beneficial bacteria before considering vegetables, whole grains and starches. Avoiding high-fiber diets initially is important if your gut microbiome is compromised, as excessive fiber will increase endotoxin levels.
If your gut health is severely compromised, focus on easily digestible carbohydrates like dextrose water for the first week or two. Sip it slowly throughout the day to support gradual gut healing.
3. Reduce exposure to environmental toxins — Exposure to synthetic endocrine-disrupting chemicals (EDCs), estrogen and pervasive electromagnetic fields (EMFs) further impairs your cells’ ability to generate energy efficiently. This energy deficit makes it challenging to sustain the oxygen-free gut environment necessary for beneficial bacteria like Akkermansia to flourish.
Further, a lack of cellular energy creates an environment in your gut that favors endotoxin-producing bacteria, damaging mitochondria and creating a vicious cycle of worsening health. By tackling excess LA, estrogens (xenoestrogens found in everyday items like plastic), EDCs and EMFs, you restore your cellular energy and start down the path toward optimal mitochondrial function and health.
4. Get proper sun exposure and boost NAD+ levels — Take niacinamide (50 milligrams three times daily) to increase NAD+ production, which helps your mitochondria generate more energy. NAD+ enables proper cell death signaling and supports your immune system’s ability to identify and remove damaged cells.
Daily sun exposure is also important as it promotes cellular energy production by stimulating mitochondrial melatonin, offering powerful antioxidant protection. Start with brief morning exposures and gradually increase tolerance. It’s important to avoid direct sunlight during peak hours (from 10 a.m. to 4 p.m. in most U.S. regions) until you’ve eliminated vegetable oils from your diet for at least six months to reduce sunburn risk associated with stored linoleic acid.
Frequently Asked Questions About Mitochondrial Dysfunction and Inflammation
Q: What is the connection between mitochondrial dysfunction and chronic inflammation?
A: When mitochondria underproduce ATP, the body perceives this energy deficit as cellular stress. This stress triggers the NLRP3 inflammasome, a protein complex that amplifies inflammation. Over time, chronic inflammation damages tissues and can set the stage for serious conditions like cancer.
Q: How does mitochondrial dysfunction contribute to cancer development?
A: Damaged mitochondria hinder the cell’s ability to undergo apoptosis (programmed cell death). When apoptosis is suppressed, abnormal cells survive longer than they should, accumulating more mutations and fueling tumor growth. Additionally, chronic inflammation driven by impaired mitochondrial function creates an environment that supports cancer progression.
Q: Why is linoleic acid problematic for mitochondrial health?
A: LA, found in most vegetable oils and many processed foods, is considered a mitochondrial poison because it impairs cellular energy production. Consuming high amounts of LA results in both gut dysbiosis (an imbalance of gut bacteria) and heightened inflammation, further undermining mitochondrial function and overall health.
Q: Can improving carbohydrate intake help restore mitochondrial function?
A: Yes. Glucose is a key fuel for energy production (via oxidative phosphorylation) in the mitochondria. By incorporating adequate, easily digestible carbohydrates — such as white rice or whole fruits — you’ll be able to support cellular energy and encourage healthier gut bacteria. This approach is especially important if your gut microbiome is already compromised.
Q: What lifestyle strategies can support better mitochondrial function?
A: Key strategies include eliminating processed foods (especially those high in vegetable oils), optimizing carbohydrate intake, reducing exposure to toxins like endocrine disruptors and heavy electromagnetic fields, getting regular sun exposure, and boosting NAD+ levels (e.g., via niacinamide supplementation). These measures help reduce inflammation, restore proper cell death signaling, and protect against chronic diseases linked to mitochondrial dysfunction.
- 1, 8, 9, 10, 11, 12, 13 Immunity, November 20, 2024
- 2 Signal Transduction and Targeted Therapy volume 6, Article number: 263 (2021)
- 3 J Clin Med. 2020 Mar 9;9(3):740
- 4 National Institutes of Health, November 3, 2020
- 5 CDC, Cancer Data and Statistics, December 3, 2024
- 6 J Hematol Oncol. 2022 Jul 18;15:97
- 7 Annual Review of Immunology April 2023, 41:301-316
- 14 To Extract Knowledge from Matter, December 7, 2024
High Blood Sugar — Are We Missing Half the Story? The Role of Reductive Stress
Reproduced from original article:
https://articles.mercola.com/sites/articles/archive/2025/03/15/high-blood-sugar-reductive-stress.aspx
Analysis by Dr. Joseph Mercola March 15, 2025
STORY AT-A-GLANCE
- High blood sugar in Type 2 diabetes overwhelms cellular machinery like a chaotic factory, creating not just oxidative stress as previously thought, but also a more fundamental problem called reductive stress. Reductive stress occurs when there’s an oversupply of electron-carrying molecules in cells, creating a “traffic jam” of electrons that can’t be processed efficiently by the mitochondria’s electron transport chain
- While traditional views focused on oxidative stress alone, scientists now understand that reductive stress actually triggers oxidative stress. It’s the initial spark that sets off a chain reaction of cellular damage in diabetic conditions
- When the main pathway for processing glucose becomes blocked due to reductive stress, sugar molecules get diverted into harmful alternative pathways, creating additional toxic byproducts and inflammation
- The combination of reductive and oxidative stress explains many serious complications of diabetes including neuropathy, retinopathy, nephropathy and cardiovascular problems — all stemming from this initial electron overload
- Understanding reductive stress offers new therapeutic possibilities. Instead of just focusing on lowering blood sugar or fighting oxidative damage after it occurs, effective treatments target the electron transport chain efficiency and/or help cells recycle NADH more effectively
Visualize a huge workshop in your body that never stops working. Every second of the day, this workshop — your cells — transforms the food you eat into the energy and building blocks you need to survive. Picture endless supplies of raw materials being delivered to this workshop. When the workshop receives exactly what it needs, it hums along smoothly, producing vital components and discarding waste at a comfortable pace.
But when it is flooded with more resources than it can handle, chaos develops that reminds you of an old “I Love Lucy” episode. Conveyor belts clog, half-finished products pile up and machines begin malfunctioning. That chaos mirrors what happens inside your cells when you have chronically high blood sugar or otherwise known as Type 2 diabetes.
Scientists once focused on how too much sugar in your bloodstream creates damage through something called oxidative stress — an onslaught of destructive, oxygen-containing molecules. While that is important, a more serious stealth problem — reductive stress — turns out to be the main problem.1 For an easy-to-understand overview of what reductive stress is, and how it’s caused, see “Redox Simplified, Part 1.”
Reductive stress was first reported in the literature just before 1990 and is only relatively recently appreciated.2 It is at least as significant as oxidative stress for explaining why your cells lose their balance under conditions of prolonged high blood sugar. Reductive stress is the hidden spark that sets off a harmful chain reaction, eventually leading to severe problems for cells, tissues and organs.
Type 2 diabetes is frequently described as a disease of “overnutrition.” People consume more caloric energy than their bodies know what to do with, so cells try to cope with that oversupply. Insulin is the hormone that helps move sugar from the bloodstream into cells for use or storage.
This sugar is primarily glucose — a simple sugar that is chemically identical to what’s sometimes called dextrose, especially when you find it as a commercially available product in a store or used in IVs. In the early stages of Type 2 diabetes, cells grow resistant to insulin’s signal, making them slow to remove excess sugar from circulation.
However, in the late 1980s, scientists began to understand that there was another, more significant explanation beyond overnutrition. They couldn’t fully explain the observed pathologies solely based on excessive nutrient intake.
While overnutrition can contribute to health problems, more commonly, we see a disruption in the cellular machinery responsible for metabolizing fuel. Essentially, the “furnaces” within cells, the mitochondria, become less efficient at burning fuel. This diminished capacity to use fuel effectively leads to a buildup of harmful byproducts and, ultimately, cellular damage.
Why Overly High Sugar Leads to Reductive Stress
Many researchers once blamed only oxidative stress for the damage caused by chronic elevated blood sugars, but the story is far more complex. A less publicized culprit called reductive stress occurs when there is an oversupply of special electron-carrying molecules in your cells.
• Too much electron-carrying molecules in your cells — One of the key carriers is NADH, which picks up electrons when sugar is broken down for energy. Ordinarily, NADH unloads its electrons in the electron transport chain (ETC) of your mitochondria. When you have too much sugar around, your metabolic pathways generate more NADH than your cells can handle. This oversupply forms a traffic jam of electrons stuck in your mitochondrial ETC.
• The impact of excess NADH — During normal metabolism, oxygen in your mitochondria eventually accepts electrons from carriers like NADH, letting ATP and water form. However, if NADH is piling up too fast or is not being recycled quickly enough, your mitochondria reach a bottleneck and start leaking electrons onto oxygen in erratic ways. That partial reaction creates a reactive oxygen species called superoxide.
• Having excess NADH causes reductive stress — This sets off a cascade that leads to excessive oxidative stress. The two stresses work hand in hand — they both push the system toward an oxidative meltdown. Realizing that they are connected helps explain many of the complications tied to long-term high blood sugar.
Cells also have backup carriers like NADPH and glutathione, which help defend against or fix routine oxidative damage. But when you have high blood sugar, these carriers are also thrown off balance, sometimes contributing further to reductive stress. So, what should be a finely tuned assembly line of electrons becomes a crowded, poorly managed factory.
How Mitochondria and Enzymes Suffer Under Excess Sugar
Under healthy conditions, most sugar flows through glycolysis and then the Krebs cycle in your mitochondria, leading to a steady generation of NADH for ATP production. In a state of chronically high blood sugar, a steady flood of sugar pours in, leading to overly high rates of NADH production.
• Influx of sugar creates electron pressure — Pancreatic beta cells and liver cells are particularly vulnerable because they possess an enzyme called glucokinase, which does not slow down as sugar accumulates. It just keeps stuffing sugar into the mill, generating more pyruvate and acetyl-CoA, and eventually too much NADH.
This leads to what some researchers call electron pressure. Think of it as building water pressure in a dam. The more NADH, the more “water” is pushing against the gates of the electron transport chain. If the gates can’t relieve that pressure quickly enough, water (electrons) spills out in harmful ways, forming superoxide and other reactive oxygen species (ROS).
• Rethinking the accepted causes of oxidative stress — Though we typically consider fat metabolism or the lack of antioxidants to be reasons for oxidative stress, it is actually an overabundance of these electron carriers, like NADH, that triggers these chains of events.
• Low oxygen consumption occurs — Low oxygen usage in cells, sometimes referred to as pseudohypoxia, can also happen under these conditions. Even though oxygen might be physically present, the cell’s ability to use that oxygen effectively stalls when electron carriers accumulate. It’s the same effect as having enough workers on an assembly line but not being able to move products forward because the packaging stations are jammed.
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When Reductive Stress Morphs Into Oxidative Damage
Too much NADH sets the stage for oxidative stress, but how does that transition really happen?
• The process behind excess NADH creation — The mitochondria’s Complex I tries to oxidize NADH — basically convert it back to NAD+ — but an overwhelming influx of NADH leads to partial electron leaks onto oxygen, generating superoxide.
• Superoxide transforms into more harmful substances — The superoxide easily transforms into other even more hazardous molecules, such as hydrogen peroxide or hydroxyl radicals, intensifying the cell’s damage. Hence, reductive stress is the fuse that ignites oxidative stress.
Researchers used to think of oxidative stress and reductive stress as opposites, but in fact, you can’t get a huge wave of oxidative molecules without first bottling up too many electrons somewhere upstream. The meltdown occurs when all these unwanted oxygen-based molecules assault proteins, lipids and genetic material within cells, blocking regular functions and straining the system further.
How Key Enzymes Become Blocked, Triggering Toxic Side Routes
Glyceraldehyde 3-phosphate dehydrogenase, or GAPDH, is an important enzyme in glycolysis. You can think of it as a traffic cop, directing the flow of carbon units down the main route for energy production.
• Reductive stress roadblocks GAPDH — In reductive stress conditions, superoxide and other reactive molecules can chemically inactivate GAPDH, jamming the normal route. That means partially digested sugar fragments accumulate, searching for an escape route. If the main road of glycolysis is blocked, these fragments slip into alternative pathways — often called branching pathways.
• Examples of branching pathways — One of the branches is the polyol pathway, where sugar is first turned into sorbitol and then into fructose. This route increases NADH and drains NADPH, leaving the cell less capable of defending against oxidative threats. Another branch is the hexosamine pathway, which decorates proteins with sugar-like attachments and can promote even more harmful byproducts.
A third branch leads to the creation of advanced glycation end products, lumps of sugar stuck onto proteins that distort them and spark inflammation.
Each of these side roads ends up producing or amplifying reactive oxygen species, so the cell quickly finds itself in an escalating cycle — high sugar leads to reductive stress, which leads to oxidative stress, which damages enzymes, forcing leftover sugar into toxic detours, fueling even more oxidative stress.
• Diabetes is the result — The cyclical meltdown causes the hallmark problems of diabetes — nerves lose function (neuropathy), eyes develop vision problems (retinopathy), kidneys fail (nephropathy) and blood vessels clog or weaken (leading to strokes, heart attacks and amputations). It’s a chain reaction that starts from too much sugar and too many electrons in the wrong place at the wrong time.
The following graph, Figure 4 from Liang-Jun Yan’s paper, “Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress,”3 published in the Journal of Diabetes Research in 2014, illustrates this process.
Consequences for People with Diabetes and Recommended Solutions
As chronic hyperglycemia persists, cells get battered by waves of destructive molecules. This environment disrupts insulin secretion, lowers insulin sensitivity and robs tissues of normal functioning. Measuring such damage often shows high levels of oxidative stress in people with poor sugar control, reinforcing that the end result of reductive stress — excess electron carriers — translates into extensive oxidative harm.
• There is a glimmer of hope — If the fundamental problem is that NADH builds up too fast, then reducing or balancing that electron overload might prevent later catastrophes.
• Addressing the root problem of diabetes — While many diabetes treatments focus on lowering blood sugar in general, or on cleaning up ROS after they form, what we really need are strategies to either curb the production of extra NADH or help cells recycle NADH back to NAD+ more efficiently.
• Other strategies that help manage diabetes — Some researchers suggest that strengthening the electron transport chain, or using dietary or pharmaceutical interventions that enhance NAD+ regeneration, can short-circuit the entire cascade before oxidative stress goes wild.
In simpler language, controlling reductive stress means improving the traffic flow of electrons in the cell, ensuring they don’t stack up to dangerous levels. If you manage the electron flow at the front end, you reduce the chance of harmful chain reactions downstream.
Putting It All Together — Why Reductive Stress Matters So Much
Prolonged high blood sugar is definitely toxic to cells, but we now see that the toxicity operates through a two-phase process — first, reductive stress (an electron overload), then oxidative stress (excess oxygen-based radicals) finalizes the damage.
• Oxidative stress is just one piece of the puzzle — The statement above modifies the classic narrative that only oxidative stress is to blame. Recognizing how reductive stress kindles oxidative stress helps us see that lowering sugar might not be enough; we also need to keep watch on the entire electron-handling machinery within cells.
• Reductive stress must be detected earlier — One of the big questions is why reductive stress has been overlooked for so long if it’s so central. Part of the answer is that oxidative stress is easier to detect with standard lab tests and known chemical markers, whereas reductive stress is more subtle, only revealing itself in how the electron carriers build up.
Also, reductive stress was first documented decades ago and then largely forgotten, overshadowed by the simpler story of oxygen-based radicals. Only with improved technologies and a deeper dive into electron transport chain dynamics did researchers rediscover how an oversupply of NADH or NADPH can disrupt everything.
In everyday life, the main message remains consistent — keep blood sugar under control to protect your cells from a damaging cascade.
• Strategies to address reductive stress — Good nutrition, exercise and regular medical check-ups all form part of the frontline in preventing reductive stress from flaring into full-blown oxidative chaos.
• The importance of studying reductive stress — Long term, the real advantage in understanding reductive stress is that it offers a new angle — one that goes beyond the usual talk of high sugar and ROS. By targeting the earliest link in the chain, you can knock out multiple problems at once, safeguarding insulin production, reducing inflammation and preserving healthy organ function.
Supplements That May Help Address Reductive Stress
Several nutritional supplements can be helpful in this regard, including the following:
• Coenzyme Q10 (CoQ10) / Ubiquinol:
◦ Mechanism — CoQ10 is a vital component of the ETC in mitochondria. It acts as an electron shuttle, helping to move electrons along the ETC and facilitate ATP production. In its reduced form, ubiquinol, it can also act as an antioxidant.
◦ Relevance to reductive stress — By improving the efficiency of the ETC, CoQ10 may help to prevent the buildup of NADH and the subsequent leakage of electrons that leads to reductive stress.
• Alpha-lipoic acid (ALA):
◦ Mechanism — ALA is a potent antioxidant that can also regenerate other antioxidants, such as vitamin C and glutathione. It also plays a role in mitochondrial energy metabolism.
◦ Relevance to reductive stress — ALA’s antioxidant properties can help to mitigate the oxidative damage that results from reductive stress. It may also indirectly support the ETC by regenerating other antioxidants involved in the process.
◦ Note — ALA exists in two forms (R-lipoic acid and S-lipoic acid), and the R form is generally considered more biologically active.
• Methylene blue:
◦ Mechanism — Methylene blue acts as an alternative electron acceptor in the ETC, effectively bypassing Complex I and III. It can cycle between its oxidized and reduced forms, shuttling electrons directly to cytochrome c and oxygen, improving mitochondrial function even when the standard electron transport chain is impaired.
Methylene blue’s ability to accept electrons makes it particularly useful in conditions where the standard ETC is overwhelmed or dysfunctional.
◦ Relevance to reductive stress — By providing an alternative route for electron flow, methylene blue helps relieve the electron congestion that characterizes reductive stress. It effectively acts as an “electron pressure release valve,” helping to prevent the buildup of NADH and reducing the likelihood of electron leakage and subsequent oxidative damage.
• Pyrroloquinoline quinone (PQQ):
◦ Mechanism — PQQ is a potent antioxidant that has been shown to stimulate mitochondrial biogenesis (the creation of new mitochondria).
◦ Relevance to reductive stress — By increasing the number of mitochondria and improving their function, PQQ enhances the cell’s overall capacity to handle electron flow and reduce the likelihood of reductive stress.
• Riboflavin (B2), niacinamide (B3) and thiamine (B1):
◦ Mechanism — B vitamins play essential roles as coenzymes in various metabolic pathways, including those involved in energy production and the ETC. Riboflavin is a precursor to FAD, and niacin is a precursor to NAD. Both are electron carriers.
◦ Relevance to reductive stress — Adequate levels of B vitamins are essential for the proper functioning of the ETC and may help to prevent the buildup of reducing equivalents.
Frequently Asked Questions (FAQs) on Reductive Stress and Type 2 Diabetes
Q: What is reductive stress, and how does it relate to Type 2 diabetes?
A: Reductive stress occurs when cells accumulate too many electron-carrying molecules, such as NADH, due to prolonged high blood sugar levels. This overload creates a bottleneck in the mitochondria, leading to an imbalance that ultimately triggers oxidative stress. In Type 2 diabetes, excessive sugar intake overwhelms the metabolic system, causing a cascade of harmful effects that damage cells, tissues and organs.
Q: How does reductive stress contribute to oxidative stress and cellular damage?
A: When NADH builds up in cells, it overwhelms the electron transport chain (ETC) in mitochondria, leading to electron leakage. These leaked electrons react with oxygen to form harmful reactive oxygen species (ROS) like superoxide and hydrogen peroxide. This oxidative damage disrupts cellular processes, impairs insulin function and contributes to complications like neuropathy, retinopathy and kidney disease.
Q: Why is reductive stress often overlooked in diabetes research?
A: Traditionally, scientists have focused on oxidative stress as the primary cause of cellular damage in diabetes. However, newer research shows that reductive stress precedes oxidative stress and acts as the initial trigger. The difficulty in measuring reductive stress and its more subtle effects led to its underappreciation for decades, but advances in mitochondrial research have revived interest in its role.
Q: What strategies can help manage reductive stress in Type 2 diabetes?
A: Managing blood sugar levels through a healthy diet and exercise supervision is key to preventing reductive stress. Additionally, certain supplements, such as coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA) and methylene blue may help manage reductive stress and prevent oxidative damage.
Q: How do supplements like CoQ10 and alpha-lipoic acid help with reductive stress?
A: CoQ10 improves mitochondrial function by facilitating electron transfer in the ETC, reducing the buildup of NADH. Alpha-lipoic acid (ALA) acts as an antioxidant and helps regenerate other protective molecules like glutathione. Both supplements aid in restoring cellular balance, reducing oxidative stress and improving insulin sensitivity in people with diabetes.