Top Tips to Optimize Your Mitochondrial Health

STORY AT-A-GLANCE

• Cancer is a metabolic disease, not a genetic one. The genetic mutations observed in some cancers are a downstream effect of defective energy metabolism in the mitochondria (the energy stations inside your cells)

• As long as your mitochondria remain healthy and functional, your chances of developing cancer are slim

• Ketogenic therapy calls for restricting net carbs to 50 grams per day and limiting protein; I recommend a limit of 1 gram of protein per kilogram of lean body mass. Fasting glucose needs to be below 70 mg/dL

If you want to avoid becoming a cancer statistic (and who doesn't?) you'd do well to familiarize yourself with the metabolic theory of cancer. In August 2016, we presented the Mercola.com Game Changer Award to Thomas Seyfried, Ph.D.,1 a professor of biology at Boston College and a leading expert and researcher in the field of cancer metabolism and nutritional ketosis.

Following is a rerun of this popular and important article and interview with Seyfried, in which we discuss his book, "Cancer as a Metabolic Disease" — an important contribution to the field of how cancer starts and can be treated.

Each day, some 1,600 people die from cancer in the United States alone. Worldwide, we're looking at a death toll of about 21,000 people daily. So many of these deaths are unnecessary — they're preventable and treatable.

Seyfried is one of the pioneers in the application of nutritional ketosis for cancer, a therapy that stems from the work of Dr. Otto Warburg, who was undoubtedly one of the most brilliant biochemists of the 20th century. Warburg received the Nobel Prize in Physiology or Medicine in 1931 for the discovery of metabolism of malignant cells.

Besides being a medical doctor, Warburg held a Ph.D., and was personal friends with Albert Einstein and many of the most prominent scientists of his time. His life's mission was to find a cure for cancer, and he actually did. Unfortunately, few were able to appreciate the importance of his findings.

Seyfried has followed in Warburg's scientific footsteps, and is conducting important research to advance this science. He has in fact exceeded Warburg's initial supposition, shedding important light on the metabolic underpinnings of cancer.

Cancer as a Metabolic Disease

The traditionally held view or dogma is that cancer is a genetic disease, but what Warburg discovered is that cancer is really caused by a defect in the cellular energy metabolism of the cell, primarily related to the function of the mitochondria, which are the little power stations within each cell.

The mitochondria were not well understood in Warburg's time but, today, we have a much better understanding of how they work.

In my view, this information is the game changer that not only treats cancer but virtually every single disease known to man, because at the core of most serious ailments you find mitochondrial dysfunction. As noted by Seyfried:

How the Metabolic View Alters Cancer Treatment

As Seyfried notes, the problem today is not that scientists and doctors cannot understand the science; it's that they cannot accept that this could be the truth behind the nature of the disease, because it changes how you approach treatment.

If defective mitochondria are responsible for the origin of cancer, and defective energy metabolism is responsible for the majority of the phenotypes, i.e., the observable characteristics of the disease that you see, then how do you treat the disease?

In my view, one of Seyfried's most magnificent contributions to this science was his compilation of research from independent and well-respected scientists within various disciplines, who conducted valuable experiments but had no clue how to interpret the results.

Seyfried put all of their work together, forming a strong scientific foundation for the theory that cancer is indeed a metabolic disease, not a genetic one, and that genetic mutations are a downstream effect of defective energy metabolism in the mitochondria.

What the Nuclear Transfer Experiments Showed

The nuclear transfer experiments in question basically involved transplanting the nuclei of a tumor cell into a healthy and normal cytoplasm (the material within a cell, excluding the cell nucleus), which include the mitochondria, the energy-generating organelle of the cell.

The hypothesis is that if cancer is nuclear-gene driven and the phenotype of cancer is dysregulated cell growth, meaning if genetic mutations are responsible for the observable characteristics of the disease, then those abnormal genes should be expressed in the new cytoplasm. But that's not what happened.

Again and again, what was observed was that when the nuclei of a cancer cell were transferred into a healthy cytoplasm, the new cytoplasm did NOT form cancer. It remained healthy and normal.

Additional evidence has been produced by Benny Kaipparettu, Ph.D., and colleagues at Baylor University. When they transplanted normal mitochondria (with its nuclei intact) into cancer cell cytoplasm, it caused the cells to stop growing abnormally. It downregulated the oncogenes that were alleged to be driving the tumor and made the cells grow normally again.

On the other hand, when they took the mitochondria from a tumor cell and moved it into a very slow-growing type of cancer cell, the cancer cells began growing very rapidly. As noted by Seyfried, "When you bundle all these experiments together, you come to the conclusion that nuclear mutations cannot be the drivers of the disease."

What About BRCA1 and Other Inherited Cancer Genes?

A common argument for the genetic theory is that cancer can be inherited; therefore it must have genetic underpinnings. Li-Fraumeni syndrome,2 which raises your risk of developing cancer at a very young age, and BRCA1, which raises your breast cancer risk, are two examples.

If genetic mutations are not the primary cause of cancer but rather a secondary, downstream effect of dysfunctional cell respiration, why and how do mutations occur? As explained by Seyfried, once the cells' respiration is damaged, that damage then leads to a compensatory fermentation, which requires the upregulation of oncogenes (cancer genes).

Damaged respiration also produces large amounts of reactive oxygen species (ROS) and secondary free radicals that damage DNA proteins and lipids (fats inside your cellular membranes). The ROS also cause mutations in the nuclear genome. So the mutations are the result of defective respiration and subsequent exaggerated ROS production.

Why the War on Cancer Has Not Yet Been Won

At present, the cancer industry is focusing on the downstream effects of the problem, which is why the "war on cancer" has been such a miserable failure.

Why Being an Efficient Fat Burner Is so Important

The ROS also target the actual mitochondria themselves, where respiration occurs, which brings us to a very important point. ROS are mostly generated through the co-enzyme Q couple in the electron transport chain. Both glucose and fatty acids produce FADH2, which can generate ROS.

In contrast, fat-derived ketone bodies produce only NADH, which increases the redox span of the co-enzyme Q couple and reduces production of ROS. Hence, ketone bodies are considered a more "clean" fuel than is either glucose or fatty acids Today, most people are burning glucose as their primary fuel, thanks to an overabundance of sugar and processed grains in the diet and a deficiency in healthy fats.

If you have less ROS being generated in the mitochondria, you end up with less mitochondrial damage and less DNA damage. So not only is switching the fuel you're feeding your body the key component of cancer treatment, but in my view it's the primary way that you prevent cancer from occurring in the first place.

Do Not Confuse Nutritional Ketosis With Ketoacidosis

Nutritional ketosis should NOT be confused with diabetic ketoacidosis (DKA), which is not a concern unless you have Type 1 diabetes. It's rare for a person with normal physiology to elevate their ketones above 7 or 8 millimole (mmol). If you have DKA, your ketones will be about 20 mmol. Additionally, your blood sugars will be very high, while in nutritional ketosis blood sugars are very low. These are clearly two entirely different states.

And whereas ketoacidosis can be life threatening, nutritional ketosis is a healthy state that helps you maintain maximum energy efficiency and reduces ROS production in your body. As noted by Seyfried, "Mitochondria actually get very healthy when ketones are metabolized as opposed to some of the other fuels, especially glucose."

For the last few decades, most natural health enthusiasts would attempt to circumvent the ROS challenge by taking antioxidants, either through foods high in polyphenols and other natural antioxidants, or supplements. I now believe this is a fatally flawed strategy that has significant drawbacks.

Rather than trying to quell the ROS after they're produced, it's far more effective to address the ROS generation at its source, which is the fuel your body is primarily burning for energy. Change the fuel, from sugar to fat, and you will generate fewer ROS.

Ketones Prevent Dysregulated ROS Production

It's not that ketones don't generate any ROS; they do, just not as much. And this brings us to yet another crucial point. ROS are not merely agents of destruction; they're also powerful signaling molecules. If you suppress them indiscriminately, you'll create biological dysfunction.

So you do not want to eliminate them. You just want to control them to optimal levels so all the signaling can occur without damage. That's what happens with ketones. When your body is burning ketones as its primary fuel, you more or less ensure that you're in an ideal therapeutic window with regard to ROS generation, so you have neither too much nor too little ROS.

Indeed, toxicity is one of the biggest failures of current treatment protocols for cancer. The majority of treatments for cancer are extremely toxic, which further exacerbates the problem. Many cancer recurrences are likely due to the initial treatment.

On the other hand, when you view cancer as a metabolic disease, you can target and manage the disease without creating systemic toxicity. As explained by Seyfried, you do this by targeting the fuels the cancer cells are using, primarily glucose and glutamine.

Most Disease Is Rooted in Mitochondrial Dysfunction

Cancer is not the only outcome when mitochondrial respiration goes awry. This kind of dysfunction also plays a role in neurodegenerative diseases such as Alzheimer's, Parkinson's and amyotrophic lateral sclerosis (ALS).

It's also at play in seizure disorders and in diabetes, obesity, hypertension and hypercholesterolemia. Most of the major diseases we're currently treating with harsh and toxic drugs can potentially be solved with proper nutritional intervention that addresses your choice of cellular fuels.

How exactly do you do that? According to Seyfried, in order to achieve nutritional ketosis, you need to reduce net carbohydrates (total carbs minus fiber) to less than 100 grams, probably less than 50 grams. I have a slightly different view on this, which I'll expound on in the next section.

You also need to reduce your amino acid content. Glutamine is the most common amino acid in proteins, and besides glucose, cancer cells can use glutamine for energy and growth as well. The combination of both glucose and glutamine creates a really "supercharged system," Seyfried notes.

In order to lower glutamine, you have to eat less protein. Also, there's a threshold for amino acids, above which you will simply stimulate the mTOR pathway, which in conjunction with insulin may wield a more powerful influence on mitochondrial dysfunction and mitochondrial biogenesis than insulin alone.

How to Assess the Health of Your Mitochondria

How can you assess the health of your mitochondria? There are a couple of ways of doing this. Seyfried has published a paper on the glucose ketone index calculator3 (GKIC) in an open access journal, which can be accessed by anyone. You can use that calculator to assess the health and vitality of your mitochondria.

The GKIC looks at your glucose to ketone ratio. Ketones must be measured by blood, not urine, and your glucose must be entered in mmol, not in milligrams per deciliter (mg/dL). "When you have a glucose ratio of 1.0 or below, you know your mitochondria are in a very healthy zone," Seyfried says.

Now, getting down to a 1.0 is quite difficult. I'm typically between 2 and 3, and my diet is about 80% healthy fats with minimal net carbs. You may need to do a complete fast in order to get that low. However, you don't need to remain in that ultralow zone for very long. On the other hand, if you have cancer, you'll want to hit that mark as much as possible.

Therapeutic Ketosis Made Simpler With a Nutrient Tracker

That strategy will likely be too extreme for most folks, unless you're faced with death or otherwise highly motivated. Rather than doing lengthy water fasting, I believe a more user-friendly strategy would be to restrict your net carbs below 50 grams per day and your protein to below 1 gram per kilogram of lean body mass. Most people eat a lot more net carbs and protein than that.

To make sure you're actually meeting these targets you need an analytical tool to do a detailed nutritional analysis of what you're eating. Otherwise, you really don't know how much fat, carbs and protein you're getting. This was my motivation for working with the developer of www.Cronometer.com/mercola, an online nutrient tracker, to create a Mercola version of the software programmed specifically for nutritional ketosis.

You can sign up and use Cronometer.com/Mercola for free. This software will make all the calculations for you, based on the parameters you enter, such as your height, weight, body fat percentage and waist circumference. You can also enter and track various biomarkers, such as fasting glucose, which is an essential measurement.

You really must keep tabs on your fasting blood sugar. Ideally, you would measure it twice a day; first thing in the morning and right before you go to bed. You want to get your blood sugar below 70 mg/dL, ideally somewhere around 60.

If your fasting blood sugar is significantly higher in the morning than in the afternoon, it's likely due to glucogenesis, which is a sign you're not getting enough protein. You need a certain amount of amino acids or else your body will start to metabolize lean body tissue to generate them. In that process, the excess gets shuttled to your liver, which is what generates the extra glucose (hence the elevated reading in the absence of food).

More Information

If you really want to dig deep into the details of therapeutic ketosis, read Seyfried's book, "Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer." If you want to start with a shorter treatise, you can read through his paper, "Cancer as a Metabolic Disease: Implications for Novel Therapeutics," published in the journal Carcinogenesis in 2014,4 or his 2015 paper in the journal Frontiers.

Hopefully, we've inspired you to consider the nutritional roots of cancer and other chronic disease. I can promise you will hear a lot more about this in the months and years to come, as I am convinced addressing mitochondrial dysfunction is the real key to solving most of our current health problems.

The good news is that optimizing mitochondrial function can be effectively accomplished through diet and lifestyle strategies like exercise. No costly drugs or invasive procedures required.

And, while we still have a long way to go, more doctors are starting to pay attention. "This is the tipping point," Seyfried says. "Many physicians are coming on board. I think things are going to start changing for the best and for the success of people."

Too many people have died and continue to die needlessly. It's time to get back on the right track. It's going to require a lot of education, but the effort is absolutely worth it. The information about how to prevent cancer and other chronic illness already exists. It's just a matter of applying it.

Analysis by Dr. Joseph Mercola – Medically Reviewed byThomas Seyfried, Ph.D.