Monthly Archives: March 2018

Fast Mimicking Diet 4: Reversing Diabetes

Fast Mimicking Diet 4, Reversing Diabetes

References: Whitehall StudyCirculationAgingDiabetes CareCell,

This is a big deal. If you read no email this year but this one, you will be well served. The reversal of diabetes is so important, it is a game changer for all of medicine. Why? Two reasons.

The first is that it is so destructive, effecitively being the cornerstone for all our diseases of modern society. We have defined diabetes by committee and decided that it really wasn’t a disease until you got to a blood level of 124 or so, measured twice, or a Hemoglobin A1c of 6.2 or 6.4 (Remember: the A1c is the percent of hemoglobin molecules with a glucose stuck on them. Red cells live 100 days, about, which makes the A1c a nice surrogate marker for your average glucose over the last 100 days.. But that is looking at a disease you might think about treating. What would happen if you decided to consider what blood sugar results in optimal function? I would refer you to the Whitehall Study from England, It showed that for every point of glucose above 86, you have a 5% increased risk of heart disease. And there is wide acknowledgement now that we need to lower blood sugar, which modern medicine does by treating with drugs. That means an optimal blood sugar should be 86. Bredesen shows abundant evidence that a HgbA1c of 5.5 is what you want if you are anxious about Alzheimer’s.

The second is that everyone has it. There are all sorts of papers saying how many millions of people have it, but that is the DISEASE. If you want optimal function, the picture is much gloomier. The simplest explanation of how your body progresses to diabetes is as follows: your fat cells become insulin resistant in relationship to their size. As you get fatter, your fat cells get bigger. You don’t make ore. And your insulin receptors get further apart, So you become insulin resistant. You raise your insulin to keep that blood sugar in control, which you can only so for so long. After a while, you run out of the ability to keep raising your insulin level. It’s as though you were only given so much insulin in a lifetime. As long as you were only burning a tiny amount a day, you can live a very long time. But it has become pretty apparant that once we get overweight, we are burning up our insulin supply faster than we can maintain for a lifetime of 100 years. And that is what we see today in modern medicine. As we age, being a bit plump gradually turns into our blood sugar slowing rising, and your being put on one pill after another until you get to age 55 or so, and then you flunk out and get put on insulin. Your islets in your pancreas look shaggy with fewer healthier insulin producing cells. And then your kidneys fail and you get on dialysis, and then you flunk and get Alzheimer’s. Till now, the key to reversing diabetes has all been about losing weight, making fat cells smaller and getting the residual ability you have to make insulin in line with your reserve of insulin producing capacity. Imagine having an insulin level of 35 when you weight 190, but a level of 2 when you weight 132. That’s what we see clinically happening.

Here is where the Fast Mimicking Diet (FMD) comes in. What would you think if I told you that the FMD turns on the genes that literally wipe out old, dead, decaying tissue and starts rejuvenation of new insulin producing cells? Yes, produces new insulin cells. We have never seen anything quite like this before. This is like the holy grail of medicine, and it’s right there in front of our faces. The FMD turns on genes that support resiliency, getting rid of old garbage that’s in the way and turning on the growth of new stem cells. This is dieting for your genes sake. And all we are asking of you is 5 days a month until you have got yourself fixed.

WWW.What will work for me. I’ve been getting older and I have a family history of diabetes. To my alarm, this year my A1c ticked up from it’s usual 5.2-5.4. I’ve already done one cycle. I’m starting cycle number two. I just came back from a trip to see old friends I grew up with in India. I’m going to send them copies of Longo’s book. My advice to you is to not trust me, or your own doctor on this topic. Trust your own lab results. Watch your own response. The data is there. This diet will eventually become the “human diet”. We will all be on a variation of it. The good news, if you don’t have any risk factors, is that you only need to do it twice to three times a year, provided you exercise properly.

Pop Quiz

 

  1. Diabetes starts at a Hemoglobin A1c of 6.2. T or F                                         Answer: true, if you call it as the disease and use current medicine’s standards. Optimal is a whole different story. If you have worries about heart disease, Alzheimer’s. autoimmune disease.. or just want to age gracefully into your 90s, you want an optimal A1c: below 5.5
  2. You can lower your A1c by losing weight. How does that work?                    Answer: your fat cells get smaller and the residual insulin you have left become in line with the amount you need to control those fat cells.
  3. If I’m getting a little older and a little heftier, what is happening to my insulin producing cells in the islets in my pancreas?                                                                                 Answer: They are getting fewer and making less insulin.
  4. How many days do I have to do this diet thing?                                                Answer: 5. Four, as best we know, isn’t sufficient.
  5. What is an optimal blood sugar?                                                                         Answer: Your family doctor will tell you under 100 or so but won’t call you diabetic until you are 126, or if they are just checking your urine, you will be normal when you have a sugar below 180 because your kidneys can reabsorb anything below 180. (I kid you not, I talked to a person this week whose doctor was still checking urine for diabetes.)

 

Fast Mimicking Diet 3: The Fasting Part

Fast Mimicking Diet 3 The Fast Mimicking

References: Longo: The Longevity Diet, [Science], Science DirectCellCell Metabolism,

I like to eat. I get hungry. What is it about fasting that makes me do better? Let’s review. Valter Longo found that there were two processes in yeast (very primitive organism) and mice (sophisticated mammalian organism) that respond in the same way. RAS and TOR. Those are the two pathways that appear to accelerate aging. Sugar turns on RAS-PKA and extra protein turns on TOR-6SK Growth Hormone Pathway. If you can down regulate the RAS pathway, you increase the rate of clearing out old, dead, malfunctioning tissues and organelles. That’s called autophagy. TOR is an internal monitor of nutrient density and controller of cell growth. Can’t grow if you don’t have enough food. Dial TOR down and cells stop dividing and go into hunker down mode. Alter those two pathways and presto, chango, you have gotten to the root cause of aging in humans. That discovery, that these two pathways are fundamental to all life on this planet, starting with yeast and moving all the way up to humans, is Longo’s key contribution to modern understanding of aging.
Fasting turns both those pathways in the right direction. It takes about 24 hours to use up the glucose in your liver, stored as glycogen. The human body then switches to burning fat from stores in fat cells. The brain and body utilize ketone bodies in a process termed ketolysis, in which acetoacetic acid and 3-β-hydroxybutyrate are converted into acetoacetyl-CoA and then acetyl-CoA. In yeast, glucose, acetic acid and ethanol, but not glycerol which is also generated during fasting from the breakdown of fats, accelerate aging. Not glycerol. Did you get that? There is one carbon source that doesn’t turn on the nutrient recognition pathway. Glycerol is the 3 carbon fragment that holds fats together in tri-“glycerides”.

Fasting for 3 or more days in humans causes a 30% decrease in circulating insulin and glucose, as well as a reduced level of insulin-like growth factor 1 (IGF-1), the major growth factor in mammals, which together with insulin is associated with accelerated aging and cancer. Fasting for five days results in a 60% decrease in IGF-1and a 5-fold or higher increase in one of the main IGF-1-inhibiting proteins: IGFBP1. This effect on IGF-1is mostly due to protein restriction, and particularly to the restriction of essential amino acids, but is also supported by calorie restriction since the decrease in insulin levels during fasting promotes reduction in IGF-1. In humans, chronic fasting does not lead to a decrease in IGF-1 unless combined with protein restriction.
Did you get all that? It’s the protein restriction that matters. Five days appears to be the time period in which maximum reduction of cancer growth factors and insulin occurs. You can trick the system with some glycerol which doesn’t register as a sensed nutrient. And we have some markers of metabolism to show your success. 5 days. Reduced protein, animal in particular. Cut the calories down to low enough to turn on and maintain ketogenesis. Sounds like about 800 a day will work. The goal isn’t to lose weight but to turn on anti-aging genes.

WWW. What will work for me. Well, I’ve finished one cycle for myself and lost 6 pounds while doing it and another two pounds over the subsequent three weeks. Not bad. I’m going to do two more cycles and then repeat my own lab tests. Glycerol makes an interesting little sport drink. It’s slightly sweet and with a bit of flavor added from a tea, it’s not so bad. I’ve bought some hibiscus tea.

Pop Quiz

 

  1. What nutrient can you consume that is slightly sweet and doesn’t trigger calorie sensing? Answer: Glycerol
  2. What amino acid turns on aging, and absence turns off aging? Answer: leucine in particular.
  3. Five day fasting results in a 60% decrease in what? Answer: IGF-1 or our Growth Hormone surrogate marker.
  4. Along with that, you get up to a 5 fold INCREASE in what IGF-1 inhibitor? Answer: IGFBP1.
  5. What lab tests might you want to know if you were getting success in your fasting methods? Answer: Glucose, insulin, IGF-1 and IGFBP-1

 

Fast Mimicking Diet 2: The Human Method Simplified

Fast Mimicking Diet 2 The Human Method

References: Longo: The Longevity Diet, ScienceGut,

Last week we heard about yeast being used to explore what genes are needed to make the right environment for longevity. Valter Longo’s hypotheses was that those same genes exist in mammals, humans included. If he could make the same changes in longevity by diet and its effect on genes in mice that he made in yeast, he would have a huge scientific win. He started looking at mice and their genetic code. Mice live about two years and start getting cancer around a year and a half. That makes a useful model.
What did he find? The exact same thing. Two key ideas. Extra sugar activate the PKA gene. That causes trouble. Mice with lower PKA activity, live longer. That simple. And extra protein activates the growth hormone receptor and TOR-6SK and increases the level of insulin and insulin like growth factor. Certain amino acids appear to be more potent at activating the TOR-6SK complex, like leucine. which then accelerates aging. That’s it. The foundation of aging down to two simple key processes. Too much sugar, and too much protein. That duo is the foundation of what Longo called his “basic juvenology research”, one of his Five Pillars of Proof.
The story is all about the nuance of glucose and protein.

Our body runs on glucose. It is our preferred food for our brain, if present. The story is all about how it is delivered and what happens to our bodies if we get too much, too fast. When you get low glycemic carbs from vegetables, your blood sugar rises very slowly and you hardly get an insulin response. (For example, it takes 19 cups of asparagus to make 50 grams of glucose). If you have a diet of broccoli, spinach and green beans, you hardly get any insulin spike at all. A substantial portion of those vegetables make it to your colon where the biome in your colon changes those coarse fiber rich foods to short chain fatty acids, just like in gorillas (See this column from 2 weeks ago). Just like with gorillas, a high fiber diet actually results in substantial increase in fatty acids, or fat. Adhering to a Mediterranean Diet appears to make this possible, all due to the activity of the biome in your gut.
A high protein diet changes your gut biome and increases many markers of cardiovascular disease,TMAO (trimethylamine oxide). So we have seen these changes from other lines of research as well.

We are even beginning to understand the incredible complexity of our gut biome. Our colon is there to take high fiber foods and digest them for us, releasing short chain fatty acids, turning low glycemic vegetables into short chain fatty acids. Bacteroidetes are more abundant in the stool samples of those eating a mostly plant based diet, while Firmicutes were more abundant in those who eat a more animal products diet. From those major families, the specific bacteria Prevotella and Lachnospira were more common in vegetarians and vegans while Streptococcus is more common among the omnivores with higher meat intake.

Can we take this to humans with specific guidelines? Well yes. This is what Longo has come up with. Protein should be about 0.31-0.36 grams per pound per day, of which about 40 grams for women weighing 130 and 60 grams for men weighing 200. Once you hit age 65, you likely need a little more protein, but not that much. Just a little.

Your diet should be rich in healthy fats like olive oil, fish and coconut oil, walnuts and almonds. These fats essentially do the same process of helping you get more calories from fat, like the gorilla. Trans fats and saturated fats are to be avoided. And there should be plenty of Healthy Carbs – the type that make it to your colon and turn into fat. They generally have a glycemic index under 20, or 45 max which would include beans (if you aren’t lectin sensitive). The carbs that get digested in your small bowel and make sugar spikes look like ground flours of any kind, sugar in particular, high fructose corn syrup in double particular, fruit juices or too much modern fruit (modern apples are nowhere near the original Himalayan apple – ditto for pears, bananas, on and on that we have altered in the last 100 years to be much richer in sugar). Most grains are just too rich in carbs to be too good for you, unless you have changed them to be resistant, usually by cooking and then cooling. Same with potatoes. The original potato from Peru was a fine food with a GI of 40. Now it’s a glycemic index of 80-95, unless you boil it and cool it making it resistant. (Is this enough to confuse you a little?)
Finally, cut your meals down to 2 and a snack. Try to fit all your food into 11-12 hours of eating and not for 3 hours before bedtime. Breakfast is NOT the meal to skip as there is plenty of evidence that that habit correlates with many illnesses.

Ok? Next week, we will discuss how to FAST and do it right so that you kick start your genes into being supercharged. It’s cool, and it works.
WWW. What will work for me. This is evidence based and I get it. I’m so fascinated that I drew my own lab tests and started doing it full bore, as much as can be done living in a modern 8-5 work world. It’s the fasting part that has my attention. I’ve completed my first 5 day session and intend to do it again. It wasn’t so hard. More next week.

Pop Quiz

 

  1. Animal protein appears to shorten longevity? T or F                           Answer: True
  2. We need animal protein to support our healthy brain? T or F          Answer: Again true. Conundrum? Yup. We get B12 only from animal sources. But nature doesn’t care much about you once you have made your babies and passed on your genes.
  3. A high carb diet is bad for you. T or F                                                    Answer: All in the details. High in low glycemic green vegetables, it’s very good for you and is actually a high fat diet.
  4. The über enemy of nutrition is?                                                           Answer: Sugar, fructose in particular when it gets above the 6% found in fruit.
  5. How much protein can I have a day?                                                   Answer: 0.31-0.16 grams per pound when under 65 A little more after. But not much.

 

Fast Mimicking Diet 1: Starting With Yeast

Fast Mimicking Diet 1: Starting with Yeast

References: Fabrizio Science 2001Science Translational MedJBCPNASGenetics,

You’ve heard of fasting and how it encourages the body to live longer. Well, sort of. The problem is, you like to eat. And eating is critical to keeping you alive. Let’s turn it around a little and come at it from a different way. Can we make the argument that we can identify the process by which changing patterns of food, including low calorie periods of time, turn on “good genes” and what are those “good genes”?
Turns out no one had looked at aging from that point of view prior to Valter Longo. He set out on his career with the premise that the way to explore healthy aging should be to identify and encourage the genetic processes by which we can build resiliency and healthy aging. He started with yeast because they live just a few days and all 6000 of their genes are known. It’s easy to make mutations and delete a gene and see what happens. Here is what he found.
In yeast, if you take away all nutrients from them except water, they live twice as long. Hmmm. If you add back nutrients, one at a time, the only one that accelerates aging… the ONLY one, is sugar. It activates two genes called RAS and PKA and inactivates enzymes and factors tha protect against oxidation. Boom, there he was. He found a key pathway in the gene signaling pathway that caused aging. And when he came out with it, as the basis of his PhD thesis, it was so new and so far ahead, no one would believe how a lowly graduate student could come up with such a significant finding, and he was ignored and avoided. He teamed up with folks looking at more complicated organisms, worms, and found much the same but to jump from yeast to humans was too big a paradigm shift for folks to believe, and thereby publish his data. It took 6 years for him to get published in Science, and another eight years to get a study on humans showing how down regulating the human growth hormone gene helped humans live longer Sci Trans Med would be published.
He discovered that dwarf yeast and mice lived 2-6 times longer, so he sought out populations of dwarf humans in Ecuador, the Laron Syndrome folks, who are tiny dwarfs that smoke, drink, eat fried food and don’t get any diseases of aging like diabetes and heart disease. Studying that population found that their defect in their growth hormone gene forced their body to go into constant regeneration mode. Studies of their brains showed that their brains were much younger in function than the rest of their bodies. That was the key. Regeneration mode. What on earth was going on? He suddenly found his ideas being accepted. Even the Pope wanted in, and he took some of his Laron buddies off to Rome to review his finding.

Starting with that research, Longo noted that aging is the risk factor that is common to all disease. The older you get, the higher your chances of getting……..you name it, cancer, diabetes, heart disease, Alzheimer’s. Hence, start with that problem. Reduce the aging pathway and those diseases will take care of themselves. That’s why the Laron stayed “healthy”, despite all their bad habits. So, can we duplicate that by changing the way we eat? Yup.
What is the simplified version that we can understand? Easy. There are two pathways that appear to accelerate aging. The Sugar pathwy turns on RAS-PKA and extra protein turns on TOR-6SK Growth Hormone Pathway. If you can down regulate the RAS-PKA pathway, you get autophagy – you gobble up old dead stuff and get rid of it. TOR-6SK is a critical monitor of nutrient density and controller of cell growth. Dial TOR down and cells stop dividing and go into hunker down mode. Alter those two pathways and presto, change, you have gotten to the root cause of aging in humans. That discovery, that these two pathways are fundamental to all life on this planet, starting with yeast and moving all the way up to humans, is Longo’s key contribution to modern understanding of aging.

How can you alter those two? Next week.

www.What will work for me. I’m enthralled with the beauty of creation. From yeast up to humans, we can follow the same biological processes down at the cellular level, and then follow them up through all biology. The Laron People have a terrible mutation in that they end up being only 3-4 feet tall, and then live to 90 with no diseases. And all of this is connected to how we eat. Next week.

Pop Quiz

 

  1. If you feed yeast one food, they die much faster. What is it?                    Answer: sugar
  2. The one process that makes years live twice as long is?                            Answer: feed them nothing but water.
  3. Who are those people in Ecuador that live to be 90 with no diseases, despite eating fried food and smoking like chimneys?                                                                  Answer: The Laron who have a defect in growth home production – and end up 4 feet tall.
  4. What two pathways do we share with yeast, and mice, and worms, and snakes, and monkeys and everything in between?                                                            Answer: TOR and RAS
  5. What do TOR and RAS do (BONUS POINTS)?                                                 Answer: RAS measures nutrients and turns of housecleaning when there aren’t any. TOR measures nutrient density and turns on “hunker-down” mode when there is little.