For this week’s blog, we are covering interesting evidence published in one of the most important medical journals, The New England Journal of Medicine. This article was published in December 2019 and had some findings that I know will be of interest to you.
Introduction to Intermittent fasting (IF)
Who has not heard of intermittent fasting? Everybody’s heard of it. It refers to an eating pattern that cycle between periods of eating and fasting.
But what about the impact of intermittent fasting on metabolism markers, such as FOXO and AMPK? Well, what is FOXO or AMPK? What are these biomarkers?
Most people think intermittent fasting may be a way of decreasing calories. When you look back at a lot of the old caloric restriction studies, especially the ones done with lab animals, it turns out they were more intermittent fasting studies than caloric restriction.
It’s not always what you think. Maybe you can lose weight, but what about the biomarkers and some things we would get with fasting?
Let’s review an article: “Effects of Intermittent Fasting on Aging and Cardiovascular Disease”. This was a science review article, from December 2019. Dan Longo was the editor, Rafael Cabo and Mark Matson were the authors of this specific article.”
https://pubmed.ncbi.nlm.nih.gov/31881139/
Studies in animals and humans have shown that many of the health benefits of intermittent fasting are not simply the result of reduced free radical production or the development of weight loss. Still, an adaptive cellular response improves glucose regulation, stress resistance, and suppresses inflammation in the cell.”
Energy Related Markers
The article went into some good detail on the cellular mechanism of Intermittent Fasting “Total energy intake, diet composition, and length of fasting contribute to oscillations on levels of bioenergetic sensors”.
I often call them markers, but these are specifically energy related. This is the currency of energy within the cell. NAD (nicotinamide adenosine), ATP (adenosine triphosphate), and acetyl CoA.
These are the currencies of the Krebs cycle, the glycolysis cycle. They are the equations and the metabolic processes that create energy for the cell. It’s the energy we live off.
FOXO regulates cell function and stress resistance, transcription of “Fork Head Box Os”. You may have heard of FOXOs.
AMPK (AMP-Activated Protein Kinase) is a highly conserved sensor of low intracellular ATP. Have you heard of sirtuins?
Sirtuins are a type of protein that regulates cellular processes, including the aging and death of cells and their stress resistance. David Sinclair was very involved in sirtuins. He’s also been involved in other biomarkers that focus on energy. He says the most popular examination of the mechanism of aging has to do with the energy production system. It’s those mitochondria.
I’ve got 65-year-old cells that have 65-year-old furnaces in them. A 65-year-old furnace can still burn and create energy if you’ve ever seen it. It still oxidizes wood, coal, wood chips, or oil.
In these cases, not so many carbs anymore, but carbon input from a low-carb diet. They are primarily fats and proteins. My little furnaces inside my cells are burning those.
Like a 65-year-old furnace, you start getting holes in this casing and get little embers out, leaving smoke and injuring other organelles in the cell.
This causes low levels of amino acids, glucose, and insulin. It represses the activity of mTOR. It results in the inhibition of protein production and stimulation of autophagy.
Intermittent Fasting and Cellular Metabolism
What are the essential activities to accomplish Intermittent Fasting? Building cell materials. We do want to have levels of amino acids, glucose, and insulin to build. But think about it.
Read a little bit more of Valter Longo’s work. He talks about it. Look at his diet. He uses low levels of amino acids in the diet and low glucose levels. Part of our goal is that we want to put the growth mechanisms of the cell to sleep.
Another necessary process is autophagy; it refers to shutting down the growth mechanisms of the cell and having the cells start recycling those old beat-up furnaces, those old beat-up mitochondria that I talked about.
There are other organelles, such as damaged parts of the endoplasmic reticulum and damaged parts of other cell components. You want the cell to start saying, “Hey, I’m hungry, or I need fuel. I’m going back to the junk pile and burning up junk.”
Intermittent fasting may help to clean things out, survive as a cell, to get energy, what happens is that they start to clean things up; we get some genetic stimulus to begin using the actual proteins that help us accomplish the repression activity of mTOR(the mammalian target of rapamycin), which is a crucial component
What does Intermittent Fasting look like?
For most people, when they say they’re intermittent fasting, they’re usually skipping breakfast.
Valter Longo has pointed out that skipping dinner is healthier, but there are social components to eating meals. We’re social beings, and most of us do better skipping breakfast because it fits into our lifestyle better.
If you expand the eat/ non-eating window, there’s another way of looking at it. It’s called TRE( Time Restricted Eating).
You can expand the restrictions and decrease your time eating in the window. As I said, the most popular way is to skip breakfast. Eat lunch and dinner between noon and 4–5 pm. That decreases your eating window to around 4,5, maybe 6 hours.
When you compare it to the standard American diet of eating some snacks, maybe eating breakfast in the morning early, like seven o’clock, then lunch and dinner. You have three big boluses of food with snacks in between. Perhaps a snack at night around 9–10 pm. You’re having 6-8 meals. They are six boluses of an insulin reaction.
Out of 24 hours, your eating window changes from 4-6 hours into 18, possibly 20. These are different perspectives in terms of the impact on our bodies.
Metabolic adaptations to intermittent fasting that’s what we’re looking for. Keep doing this daily. Lower the increased time restriction and smaller eating window.
Energy restriction for just 10-14 hours results in depletion of liver glycogen stores. It’s not complete depletion, you’re not going to go immediately ketonic, but you get significant restriction.
As many of you know, it takes a couple of days to get all of the glucose in the liver, or glycogen in the liver, depleted.
We’re talking about a small daily dose of intermittent fasting energy restriction for 10-14 hours that results in the depletion of liver glycogen stores and the transformation of triglycerides to free fatty acids within fat cells.
A few can last for days, as the literature suggests. I’ve personally done a good bit of that for years. I’ve done a 28 to 40, 24 to 48, 36-hour fast, and even 72 two-hour fast. But 24- 48 hours or 36 -48 hours weekly, most often.
I’m not doing that right now. I’m into more of an intermittent fasting stage.
It’s hard when people ask me, what can you do next? Have you done prolonged fasting? It’s something to consider. Get Freestyle Libre or a Dexcom 6-7 and watch your blood sugars. Look at the situations that make it go up. Eat, sleep and exercise to the glucometer.
Don’t look at the limits they set. They set those limits for people that have out-of-control insulin-dependent diabetes. By the time you have that level, you should have received a continuous glucose monitoring device long ago.
I think the FDA should not require a prescription for a CGM. With health, the thing that kills has these blood sugar spikes. People have blood sugars 180-200 hour after hour, day after day, and they don’t know it.
Fat Metabolism During Intermittent Fasting
Let me predict a question, not so much answer it, for those interested and focused on the triglyceride over HDL ratio. The immediate early problem causing a decrease in HDL is losing large fluffy HDLs when you have too much insulin. Then you replace cholesterol with free fatty acids in the large fluffy particles. Next, you lose those large fluffy particles.
The point would be you would think that free fatty acids might be a challenge in terms of a healthy metabolism. No, it’s not. I think the issue we’re going to find is that it depends on where the free fatty acid is. If the free fatty acid is in the sizeable fluffy HDL particles, that’s a problem.
If we’re burning them within the fat cells, it’s a good thing.
Energy restriction for 10-14 hours a day results in the depletion of liver glycogen stores and the transformation of triglycerides in the fat cells to free fatty acids. In other words, you’re breaking down the fat stored in your fat cells.
Free fatty acids released in circulation produce ketone bodies in the liver, which are then used for energy production. Energy restriction stimulates mitochondrial biogenesis, i.e., Making new mitochondria and uncoupling. So, they are the mechanisms of improved organ function.
Let’s go a little bit deeper about the science of intermittent fasting. Cells and organs change from glucose metabolism to free fatty acids and ketones.
What’s the most popular term you hear on the internet? Fat adapted-what you’re doing is stimulating a transition from glucose metabolism to free fatty acid and ketone metabolism.
Yes, your body uses different proteins to accomplish the different types of metabolism.
For example, a car needs a different engine to burn diesel fuel than it needs to burn gasoline, or it needs to burn led versus unleaded. It’s another mechanism if it uses electricity and a battery.
Like cars, we need to retool our engine to change our diet from glucose or carbs to free fatty acids and ketones. This is the low-carb type of diet. During energy restriction, cells adopt a stress resistance mode.
When there is stress resistance during energy restriction, cells adopt a stress resistance mode by reducing insulin signalling and overall protein production. You have decreased protein production and decreased insulin signalling. So far, you have gotten a decrease in that growth component.
This is considerably different from the previous paradigm of caloric restriction. When it comes to weight loss, it ignores insulin response. Neither of the studies we discussed today is looking at weight loss. They’re looking at the biomarkers of the health of cell metabolism.
The Importance of Muscle Mass
One of the things that we have is a loss of muscle mass. Insulin resistance is the primary cause of death and disability. Metabolically active muscle mass is a significant underlying safety valve for insulin resistance.
You want to decrease body fat, but you want to increase muscle mass. Do you want only to lose weight? A lot of people get too hung up on losing weight.
Don’t get too caught up in having a BMI of around 25. If you’re at a healthy weight, you’re usually going to have a few people telling you that you look skinny and sick. If you’re not hearing people tell you, you’re probably not thin enough.
You don’t need big muscles to have strong metabolically active muscles. That’s what we want. Why do we want metabolically active muscles? What does that have to do with insulin resistance?
Active muscles bypass ailing insulin receptors. I’m more concerned about the muscle, the balance of muscle to fat, and the metabolic activity of the muscle tissue than I am about muscle mass itself.
Bioindicators and Future Challenges
One of the things that you want to look for in decreasing key bioindicators is IGF (insulin-like growth factor). When you’re doing intermittent fasting and improving your fat adaptation, you are getting regular decreases in insulin signalling.
One of the insulin-type signals is IGF (insulin-like growth factor). Upon recovery from fasting,
Eating and sleeping glucose levels increase
Ketone levels plummet
Cells increase protein production and begin growth and repair.
Another challenge I have been asked before is if Intermittent Fasting is affected by cryotherapy. My answer is It’s not well researched. There is science, and good science with heat shock proteins and temperature label proteins.
In those, they looked at saunas and cryotherapy. There is evidence. When you look at some bioindicators such as FOXO and AMPK, there is significant evidence that both cryotherapy and saunas have a positive difference.
I would assume it’s like many other things biologically: is there an additive effect, a multiplicative effect, or a subtractive effect? I don’t know the answer. I wouldn’t be surprised if it were a multiplicative effect, but I’m not going to try to guess that.
More apparent is that intermittent fasting and exercise improve mental and physical performance. Here’s where the article becomes interesting. The authors became a little bit editorial. They started saying,” if this is true in terms of science, why don’t doctors know about it?”
Intermittent fasting is not usually taught in medical school. The training programs for “experts” that are supposed to understand this don’t know yet.
One of the significant components of this article is a plea to go ahead and start changing physician training programs. It positively affects obesity, diabetes, cardiovascular disease, and cancer.
Intermittent fasting prescriptions are lifestyle prescriptions for early intervention. They are handy for those with overeating and sedentary lifestyles.
A patient can be evaluated by experts in nutrition and psychology, plus frequent contact with medical staff for a minimum of four months. They will be monitoring the body weight, glucose, and ketone levels.
The challenge is getting this information in basic science for our doctors; the following step is to guide doctors to take this information to patients.
If you found this article helpful and want to start taking steps toward reversing your chronic disease, Dr. Brewer and the PrevMed staff are ready to serve you no matter where you’re located.
To find out more, schedule a consult here: prevmedhealth.com
REFERENCES:
1. https://prevmedhealth.com/is-a-low-carb-diet-related-to-coronary-artery-calcification/
2. https://prevmedhealth.com/homocysteine-methylation/
3. https://prevmedhealth.com/does-plant-based-diet-cure-diabetes/
4. https://prevmedhealth.com/how-to-stop-ghrelin-the-hunger-hormone/
5. https://prevmedhealth.com/plant-based-vs-sugar-free-whos-right-how-to-use-food-labels-right/
6. https://prevmedhealth.com/can-type-2-diabetes-be-reversed-with-low-carb-diet/
7. https://prevmedhealth.com/the-3-biggest-diet-mistakes-theyre-not-food-choices-part-1/
8. https://prevmedhealth.com/resveratrol-sirtuins-nmn-is-david-sinclair-reversing-aging/