Feeling Tired All The Time: Blame Ceramides

April 19, 2021

Energy a Bit Low? Blame Ceramides

Do you feel washed out and tired after a meal, or at the end of the day? Dragging around, wishing you had a pick-me-up to get some get-up-and-go? Is your energy level curiously just rotten? Read this.

We are beginning to get a better understanding of how our energy flow works through understanding core metabolic processes right down in our mitochondria, our local energy factories. (Remember, you are 10% mitochondria! Your heart and brain are closer to 30%.). Mitochondria make energy in the form of the molecule ATP. So far, so good. But here are some guiding principles in making energy I bet you weren't aware of. Did you know that your mitochondria are really happiest if they can switch back and forth between running on fat or running on glucose? Did you know that they do better when you are on just one pure source of energy (glucose - carbs) or fat ( beta-hydroxybutyrate.) and not mixed. When you mix sources of fuel, it's like having two hoses filling your gas tank on your car. Something overflows. You get more reactive oxygen species (ROS) and that makes for more damage? Did you know that you start to drift into ketosis if you don't eat for 12 hours? Yup, and more ketones at 14 and even more at 16. But too much of fat, carbs, protein all at once, a typical American big meal, and your mitochondria get overwhelmed with too much fuel. And some of if is just plain bad.

Bad fuel #1 is fructose. Now, through most of human history, we got ripe fruit (hence fructose at about 5-6% of ripe fruit) only in September for a few weeks. Or, for any of us with a mulberry tree in their yards, you can imagine snarfing down mulberries all day long for about a week in July. We only got sugar, half glucose, and half fructose, in about the year 1500 or so, and only ramped up to 120 pounds a year each in the last 40 years with the addition of high fructose corn syrup. Fructose at such quantities is a new phenomenon to our mitochondria. The problem with fructose is that we don't have a way to slow it down. It goes straight to your liver, kabam! Your liver cannot turn it away. We exhaust our liver cells that frantically try to protect themselves by making fat and scavenging ADP into AMP and then uric acid. If you have fatty liver or high uric acid, you are probably well-served if you seriously examine your sugar intake because you are tip-toeing along the edge of liver failure. If you don't believe this, watch the movie "Super Size Me" and see someone who almost died from eating at MacDonald's three times a day for a month.

We now know how your liver cells protect themselves. They make ceramide fats and palmitic acid (16 carbons long) from all that fructose. Ceramides are stiffer molecules than most fats, making your cell walls more rigid and less capable to taking up arriving nutrients. Ha! Short-term strategy works. It saves the cells. But another, more insidious event happens. Ceramides block the insulin receptor, in part because of their stiffening effect on the cell membrane. And that, my friend, is how insulin resistance gets started. Your rising level of insulin corroborates with inflammation, and you now have adult-onset diabetes off to the races. With high levels of insulin in your blood, your fat cells get the message not to open up and share their fat. You have the perfect double whammy to blocked glucose uptake (so less energy) and locked fat cells (less energy).

You are in a dilemma. You have plenty of stored energy. Just check out your fat tissue. But you can't get to it. And the only, only way to feel good is to eat enough glucose to get huge swings in blood sugar and then plunges thereafter. See-saw, see-saw. And you are exhausted to boot.

Once you understand the mechanisms, you can find the way how to climb down off this cliff and get your mitochondria back to working. You can measure your ceramides if you are curious. You can certainly measure your A1c to see how "diabetic" you are. You can measure your insulin level. It should be below 7 at the worst. Five would be better.

Key principles to fixing yourself is stopping the fructose and slowing way down processed carbs. Then, focus on rebuilding your mitochondria's ability to be metabolically flexible by stretching out the time between meals, particularly at night. That way you burn up all your carbs and get practice at switching over to fat. Add more green vegetables that also make beta-hydroxybutyrate and you ease away from glucose carbs. Add olive oil. Reduce your protein down too. And all those together will get you back to metabolically flexible, with more energy and fewer ceramides. You can do it.

Did you know that ceramides predict your risk of heart disease more accurately than LDL cholesterol? Yup...but that's for another day.

www.What will Work for me. How to lower ceramides? Well, well....that's the question. Start with cutting the sugar out of your diet. If you wanted to really cut the sugar, that means you have to take on ketchup and peanut butter too! Eating extra olive oil in a Mediterranean diet has been shown to reduce heart disease commensurate with its ability to lower ceramide blood levels. More green vegetables in your diet delivers more beta-hydroxybutyrate to your mitochondria, slowly. Intermittent fasting, compressing your calories into 8 hours does it too. Hmm. I'm fasting for 5 days a month. Perhaps I need to learn to navigate past breakfast too. I found a ceramide blood test on Goodenowe's plasmalogen test. Mine was higher than I like. Bummer.

References: JAHA, Nutr Met CV Dis., Nature Metabolism, FASEB, American Coll Cardiology, Mol Nutr Food Res. , Circulation, Biochem Biophy Acta,

Pop Quiz

1. What are ceramides? Answer: they are a rigid fat that makes membranes firmer, or stiffer. (Not good)

2. What is the key means by which you make them? Answer: Eating fructose in the form of too much HFCS, table sugar, hidden sugar, fake names for sugar (like dehydrated orange juice), and forcing your liver to make palmitate, which then hits your mitochondria hard.

3. What would your mitochondria prefer? Answer: Mitochondria want to get back to metabolic resiliency and the ability to flex between carbs and fat. You can do that by compressing calories into 8 hours a day. You naturally do it when you exercise to exhaustion. You get there faster if you eat more vegetables and more olive oil.

4. If your mitochondria get overwhelmed and your cell responds by making ceramides, what happens to your ability to make ATP energy? Answer: It goes down. So do you.

5. Can I measure ceramides? Answer: Just emerging. Not yet in the major labs and certainly not in your regular clinic. The Mayo Clinic is all hot on it and has it. Goodenowe measures them with his blood panel. (www.Prodrome.com).