Monthly Archives: May 2015

Inflammasomes – a Primer on Inflammation

Inflammasomes: a Primer on Inflammation

Reference:   World Jr Diabetes, Scientific American May 2015,

Diabetes, gout, Alzheimer’s, asbestosis, erectile difficulty, heart attacks all have something in common. They are primarily diseases of inflammation. Yup, inflammation is the problem. (Redness, swelling, pain, warmth) All of these “diseases” share a common pathway. They may affect different organs (fat tissues, liver, joints, brain lung, heart) but they share a common pathway on how the illness comes about.   That changes the way we think about them. Instead of treating the organ, it’s time to start thinking about treating the underlying pathway.   That means we have to understand the underlying pathway. Inflammation.

What is inflammation?   Everyone is familiar with “stranger” inflammation. When a bacteria invades your body because you cut your finger, your innate immune system recognizes that it is a stranger, just like a virus, a parasite or a fungus, and your innate system puts out signals that danger is at hand.   Besides “stranger” initiated inflammation, there is also “danger” initiated inflammation. If you crush a cell with trauma, pieces of DNA, or ATP or fatty acids show up in the space between cells where they aren’t normally present. Your guardian immune cells assume that “strangers” must be around for damage to be there, and also set off the initiation of inflammation.   Beta-amyloid in your brain, uric acid in your joints, cholesterol in the wall of your arteries can all the set off the same sequence – without a stranger being there to start it all. See the common pathway? The core concept is that seemingly common things, in the wrong place in your body can also inadvertently set off the fire alarm.

For the last decade or so, we thought there was a hopeless maze of signaling that was complex beyond comprehension. Not so. There is a common pathway.   Certain cells called macrophages have the responsibility to eat up “danger” and digest it. They are our body’s garbage trucks.   Here is where it gets interesting. These macrophages respond to broken bits of DNA, or RNA or other DAMPs (Danger associated molecular patterns) with two patterns. One is to initiate the production of danger signals. The other pattern is to assemble a factory to process those signals. That factory is called the inflammasome.

The job of the inflammasome is to process the chemical signals of inflammation and activate them. Finally, it ships them out of the cell to call for help and keep the process going.   IL-18 and IL-1β are the two principle signaling molecules. Those two compounds circulate around, increasing blood flow, making tissue swell and all the other processes of what we call inflammation.

Now, if you want to sound particularly savvy, you can say the phrase, “I’m going to suppress my NLRP3 inflammasome today.” the next time you are offered a brownie and you really didn’t want the carbs.   The modulation of inflammasomes is the future of medicine.   The NLRP3 inflammasome may be one of the most influential because it is the one in Alzheimer’s that responds to amyloid and goes about killing off brain cells. And why is it important?   Because your can shut it down and turn it off by a chemical called beta-hydroxybutyrate. And what is beta-bydroxybutyrate? It’s a ketone body, release by fasting and eating a low carb diet.

WWW.   What will work for me?   Hmmm. I can turn off the inflammatory process by fasting? That’s no fun. But a low carb diet is good for me? Yup, this is how it works.   On a low carb diet, your body turns on fat consumption, and that releases the ketone called beta hydroxybutuerate.  And that turns off your inflammasome.   So, practice this phrase with me. “I’m turning off my NLRP3” as a way of giving yourself the willpower to resist that almond extract flavored chocolate chip triple chocolate chewie gluten free brownie sitting in the fridge.   I need the practice, because I had four of them yesterday.

 

Pop Quiz

  1. Inflammasomes are the factories our bodies make inside of cells that start the process of inflammation. T or F

True

  1. Inflammation is when your tissue gets cold, white, quiet and numb. T or F

False. Red, hot, painful and swollen

  1. Your body can respond to “danger” and “stranger” signals in the same way. T or F

Sounds like you are getting it

  1. The particular inflammsome called NRLP3 can be turned off by fasting. T or F

In a nutshell, that’s it. The ketone body called beta-hydroxybuturate is a ketone body you naturally make when you are digesting and releasing fats – and that turns NLRP3 off

  1. Inflammasome explain how many diseases are caused by the same cellular process – just showing up in different cells and tissues. T or F

Yes – this common pathway gives us reason for much more hope at turning those diseases off.

Get a Grip on How Long You Will Live

Get a Grip! Live Longer

Reference:   Lancet April 2015,  Economist May 2015

Want to get an accurate measure of how long you will live?   Give a handshake. Your grip strength will convey your prognosis. This is your most accurate gauge of longevity. How do we know?

Published this week in the Lancet, Darryl Leong from McMaster University in Canada reviewed his data from the PURE (Prospective Urban Rural Epidemiology) study and found the accuracy of this prediction. They measured grip strength in 142,861 people, ages 35-70, in 17 countries who were willing to be followed prospectively for longevity, mortality, cause of death, injuries, falls, fractures, hospitalizations, the works.   They used a very simple and reproducible measurement with the Jamar Dynamometer to measure grip strength.

The study used data from rich, poor and in-between countries.   Canada, Sweden and the Emirates were considered rich.   Bangladesh, India, Pakistan and Zimbabwe were poor and Colombia, South Africa, Poland and 7 others were considered in-between.

They did find cultural differences. Apparently the Swedes take delight in squeezing hard, and Pakistani’s are very gentle but the prognostic value of the strength still pertained.   On average, a person’s grip strength is about 300 newtons.  For every 50 newton drop in grip strength the participants showed a 17% increase in risk of dying, mostly from heart disease.   It also showed an association with stroke and heart attack.   The researchers corrected for age, education, alcohol and tobacco consumption.

Now, grip strength did not predict hospitalization for pneumonia, or mortality from falls.   One would think falls would be correlated, as weakness would seem to be predictive of risk.

Now, this news has raised quite a ruckus on the Economist web site because there are cultural differences between societies. In South Asia, you greet a person respectfully with two hands in front of you – no touching. Shaking hands is a western thing. But the data still holds.

My interpretation is that heart disease is strongly correlated with mitochondrial health. Your heart cells are 33% mitochondria by volume and their health is central to heart health.   As you get fit, the number of mitochondria both increase and get healthier.   Regular muscle cells go from 200 mitochondria to 400 when you get “in shape”. And your fitness overall is transmitted in your handshake.

As research gets down to the nitty-gritty of how fitness benefits us, we will get more details. The topic of taking care of your mitochondria will become the means of coalescing this body of knowledge. For now, you can rest comforted if you supplement yourself with a bit of CoQ10 to help protect your mitochondria, and get fit. This is where statins yield their havoc, they deplete CoQ10 dramatically. I don’t care if you aren’t skinny, I do want you to be fit.

WWW. What will work for me. Because I’m over 50, my CoQ10 is starting to fall. I take 100 mg a day. And I exercise. Mostly walking, but some running, and some gardening, some tree lopping, some mulching.   I need to find a means of getting sweaty more often so that I get a bit more fit. And I’m going to start measuring your hand strength in my office.   Come on down, crush my fingers.

 

Pop Quiz

  1. Grip strength is the best predictor of how long I will live? T or F

That’s it in a handshake

  1. Fitness all over probably correlates with strength of handshake. T or F

True

  1. Exercise increases the mitochondria in our cells. T or F

Exactly right. See where I’m leading you?

  1. Number of mitochondria means my cells can produce more energy and do their function better, aka, squeeze harder. T or F

Bingo

  1. The strength of my hand squeeze isn’t what’s making me live longer, it’s the fact that I’ve gotten fit all over, and that is just plain good for me. T or F

Bingo

Triglycerides/HDL Ratio – the Best Measure for Heart Disease Risk

The Best Cholesterol Predictor for Artery Disease

Reference: Gaziano Circulation 1997 Lemos de Luz Clinics Wan PLOS April 2015

You want to know how to predict your risk for heart disease, right? Half of us die from it, so having a bit of a warning is a useful thing.   You go to your doctor and get told that you should be on a statin. You don’t know what to say.   Should you, shouldn’t you.   That’s the conundrum.

Want some guidance?   Of course! You want to know the single best predictor for developing heart and vascular disease.   And you want to know how to change it and manage it.   Well, that’s a tall order, and now we know the answer.   And it’s NOT your LDLs and total cholesterol. We focus on LDLs because we have a 30 billion dollar industry of lowering it with statins.

The number you want is your TG(triglycerides)/HDL ratio.   The reference is above. The authors in the Clinics article took 347 high risk patients, most in their later 50s with total cholesterols over 200.   The examined the extent of their coronary artery disease by catheterization and correlated the findings with their lipids.   Because HDLs are known to be protective, and triglycerides known to be risky, the TG/HDL ratio is an attractive summarization to look it.   What the authors found was that this ratio is more accurate than the Total Cholesterol or LDL measures, which we usually use.   This study confirms the landmark first study by Gaziano that identified this ratio as being the best.

Now we have a follow up confirmation about mortality from Wan in PLOS published just last month.   They found the TG/HDL ratio to be the most predictive ratio for subsequent mortality.   After open heart surgery, they grouped their patients into three groups by tertile, (Top third, middle and bottom) and found a 5.32 fold increased mortality for those in the top third over the bottom third.

Now, here is the kicker.   You can get yourself from the top third to the bottom third in about a month with the right diet.   I’ve done it.   You have to stop eating carbohydrates that flood into your body too quickly.

This confirms the hypothesis that your blood fats are completely dominated by the carbohydrates you eat.   When you overwhelm the ability of the body to burn carbs, your insulin goes up, your liver starts to manufacture fats and your blood fats start going up.   Triglycerides reflect that you have so much fat being made that your LDLs can’t even pick it all up, so your blood starts being filled up with triglycerides. There is no drug for that. But you have choice. You can stop eating those carbs.

What food should you eat instead.   Ironically, exactly the foods that look like what is in your blood is what you should be eating to cure your bad blood fats: fat.   If you switch to a diet of 70% fat and less than 20 grams of carbs a day, you can cure your elevated triglycerides in the twinkling of an eye.

There have been some 20 articles published confirming this concept so it’s not new, but it should be considered the main method by which we confirm your risk.   When you get your cholesterol measured, make sure you know those numbers first, not your total cholesterol or your LDLs. Focus on your HDL and your triglyceride.   And then, aim to get your ratio to ONE.   One.   1.   Yes, ONE.   With that, you will be the safest and the healthiest.   Simple.   Just stop eating carbs and remeasure and you can be safe within a month.

WWW. What will work for me.   I’ve done it. I wanted to lose weight so I went on a 70% fat diet. My HDLs went from 29 to 59 in just three months. (I wasn’t measuring monthly).   My triglycerides went from 103 to 49. That makes my ratio 0.83. (Down from 3.55)   Yippeee!   I am now down 30 pounds and don’t need to lose any more weight so my new challenge is to figure out food that doesn’t make me regain weight.   Last night for supper, I started with 4 oz of cream cheese so I kept my fat up. Delicious.   No bread, no potato, no rice.   Short ribs, floating in fat, and avocado salad with olive oil dressing.   Sorry you couldn’t have it with me.

 

Pop Quiz

  1. Total cholesterol is the best measure for your risk for heart attack and vascular disease. T or F

If you said true, read this column over again. No, false.

  1. HDL is typically considered your “good” cholesterol. T or F

True

  1. The best risk measure for future cardiac mortality is your Triglyceride/HDL ratio. T or F

That’s it

  1. The means you want your triglycerides to be LESS than your HDLs. T or F

Perfect. With that, your risk of heart attack is less than 20% of the rest of us.

  1. The best way to have low triglycerides is to eat less carbs. T or F

Bingo. Eat fat instead.   And lower your risk for heart disease.

  1. That means the best way to improve your heart disease risk is to do exactly the opposite of what we have been telling your for 40 years. T or F

True

What Happens When I Cheat? With Insulin…

Hunger and Insulin, aka: What happens when I cheat.

Reference: Rodin, Health Psychology, Schloegl Diabetes Metab Res Rev

What happens with appetite and insulin when I’m on a low carb diet, high fat diet, and then eat some carbs (cheat)?   If I read the medical literature, there isn’t a clear consensus because it gets so complex, you get lost in a maze of contradictory claims and literature. There are many hormones that affect hunger and appetite, and the maze becomes confusing.

I am putting forward a hypothesis there in which I will insert the facts, as I understand them, in order to attempt some accurate simplification.   See if you agree or disagree and send me your thoughts.

My hypothesis is that eating a small amount of glucose (or flavor sweet), when you are in ketosis, will make your insulin burst up, and lead you to eating MANY more calories because you get much more hungry right away.   In this situation, insulin increases appetite.

  1. Losing weight reduces the size of your fat cells, lowers your blood glucose and reduces your risk for heart disease, cancer, Alzheimer’s, stroke. Hmmm, I want to lose weight.
  2. To lose weight, you must burn more calories than you consume.
  3. There is good evidence that high fat diets turn off insulin and assists weight loss from fat cells – which neither low fat nor high protein will do.
  4. High fat diets lower insulin and blood glucose levels promptly, resulting in reduced calorie intake, but opening up fat cells. Aka: weight loss.
  5. Ketosis results from high fat intake, with low protein and low carb intake.
  6. Ketosis means you are burning fat, either from diet or fat cells, but your fat cells are open and releasing their stored calories. You can lose weight.
  7. Exercise is a potent form of insulin substitution, so your insulin goes down and stays down, relative to a sedentary person, for at least 24 hours.
  8. The brain can run on ketones just fine, but will switch back to carbs on a moments notice. (Insulin levels < 5)
  9. To get back into ketosis takes a couple of days – up to 10.
  10. Once exposed to carbs, insulin level rises and appetite goes up. (My teleological explanation for this is the brain senses glucose, which in human history meant it was September-October, the season to gain weight to prepare for winter. Time to gorge.)
  11. Once we put on weight, our fat cells get insulin resistant and our signals get all messed up. Insulin then has no effect on appetite, or increased effect, but we have high insulin levels relative to ketosis season. (Insulin > 5)
  12. Modern medicine calls normal insulin 2-24.   Normal is <5. Most modern American’s are badly insulin resistant: hence we are getting heart disease.
  13. Someone in ketosis will instantly switch to “Gorge Mode” when given enough carbs to stimulate insulin. (Chocolate cake) At this point, insulin turns on appetite.
  14. A TINY dose of insulin reverses ketosis (both in dieters and in diabetics in ketoacidosis. Dieters still have an alert, functioning pancreas, so ketosis is healthy and natural.)
  15. You can stay in ketosis longer by eating 20 grams of carbs from spinach (low glycemic index) versus the alcohol in beer (which gets metabolized faster than glucose) or orange juice (pure sugar – bursts into your liver), or bread.
  16. Cheating once a week may be sufficient for you to plateau and stop losing weight.  Cheating with as little as a cashew snack (which you thought was all fat and ignored the carb content) might do the trick and sabotage your efforts.

WWW.   What will work for me.   I find I see all these changes in myself when I follow a ketogenic diet, and then experiment with having some chocolate cake.   I can feel the pull of appetite, which is very hard to resist.   On some days I can, and some days I can’t.   What starts out as a great day, with good fat content, can degenerate into a spasm of gorging on too many calories when I have a chocolate truffle, a piece of cake, a half scoop of ice cream.   Before I know it, I’ve eaten other foods in addition.     I would love to hear from anyone with any evidence to the contrary.

Pop Quiz

There is consensus in the medical literature on insulin and appetite. T or F

False. It’s all over the map, because no one has identified normal insulin.

  1. Normal insulin should be defined by what state of metabolism you are in, with < 5 being normal when you are trying to lose weight, and >5 when you are trying to gain weight to make it through the winter.

T

  1. Exercise confuses everything, but is explained by it’s persistent insulin like effect. T or F

True.   I may be hungrier, but I’ve burned more calories.

  1. Ketosis is our natural state during winter? T or F

True, until 10,000 years ago when we got civilization and started storing carbs to spread around all year.

  1. All of our modern diseases can be traced back to the dysfunctional metabolism too many carbs cause in our blood.

That, my friend, is true.