Carbs: Friend of Foe? (Are Carbs Making You Fat?) – Nutrition Crash Course Part 4 of 7
This is Part 4 of a 7 Part Nutrition Series. You can find the other parts here:
- Part 1: https://grahamtuttle.com/2021/02/the-big-3
- Part 2: https://grahamtuttle.com/2021/02/nutrition-101
- Part 3: https://grahamtuttle.com/2021/03/fats
- Part 4: https://grahamtuttle.com/2021/03/carbs
- Part 5: https://grahamtuttle.com/2021/05/cholesterol
- Part 6: https://grahamtuttle.com/2021/07/gut-health
- Part 7: https://grahamtuttle.com/2021/07/what-to-eat
In this part we are going to discuss the highly debated Carbohydrate. While it’s become part of the cultural lexicon to blame carbs for everything from causing diabetes to those extra 20 pounds of bodyfat on your midsection,how much of that is actually factual? In this article/podcast I’m going to break the entire conversation down into something that is hopefully palatable and full of useful information so that you can have a better understanding of the role that carbohydrates play in the body.
To paint the big picture up front for you, I’ll try to summarize the entire article here. Carbs do not cause diabetes, do not make you fat, and are not the sole cause of metabolic dysfunction. Carbs are also not essential for survival – while there are essential fatty acids and essential amino acids, there is no such thing as an essential carbohydrate. Ultimately, pathological insulin resistance, metabolic dysfunction, and cardiovascular disease are caused by caloric overfeeding from processed carbohydrates and excess Poly Unsaturated Fatty Acids in the presence of a sedentary lifestyle.
I’ll break that down much further over the course of this article, but if there was one thing you can take away from this it’s that the Unholy Triad of metabolic disease is processed carbohydrates, refined fats (mainly Omega 6 Poly Unsaturated Fatty Acids (PUFA’s)), and sedentary lifestyle. My goal in this is to help you understand that carbs are not “bad” and the solution is not as simple as “eat a low carb diet”!
Let’s first start by defining what we even mean when we’re talking about carbohydrates.
Carbs are one of three macronutrients. Essentially, they are simple sugars grouped into different combinations. Think of it like Legos. While you can stack a bunch of Legos together to make a more complex configuration, the building blocks are the same. When it comes to carbs, each “Lego” is a monosaccharide, or the basic simple sugar. Complex carbs are just bigger “Lego” structures. Ultimately, all carbohydrates are eventually digested down into these single “Lego” units to be absorbed and metabolized in the body. They are then directed for use in certain tissues or packaged for storage.
The big distinction I want to make up front is that there is world of difference between processed carbs and the carbs that are found in whole foods. Processed carbs have been refined or manipulated to strip away the intrinsic components that would otherwise make them less palatable. In other words, carbs found in whole food sources are packaged with fiber, protein, or a form of grain that slows or limits digestion. Refined flour or sugar, for example, are highly digestible. While that may sound like a good thing, your body did not evolve with these food sources. As a result, the normal satiety and digestion signaling pathways that would typically limit over consumption and direct proper absorption are disrupted, resulting in increased insulin activity and weight gain.
Put simply, while refined carbohydrates taste good and can play a potential role in athletic performance that uses glucose as a substrate for energy, these foods have no place in your diet. Whole food sources of carbohydrates are a different matter. They are fine to eat in moderation assuming they do not cause negative side effects or otherwise limit your ability to get nutrition.
The bigger issue is that most people do not understand the root causes of pathological insulin resistance, metabolic dysfunction, cardiovascular disease, and systemic inflammation. As a result, carbs get the blame.While an excess consumption of carbs is part of the equation, it’s not that simple. Let’s break it down.
First, let’s tackle pathological insulin resistance. Before we jump in, let’s get a better understanding of what Insulin is. Commonly referred to as the “hormone of storage”, Insulin has several other roles in the body. Primarily Insulin functions as an anti-catabolic signal in that it prevents the breakdown of tissues. Insulin is tasked with ensuring that there is always some form of energy available.
Insulin is released in response to rising levels of glucose in the blood. This generally happens when carbohydrates are broken down, but it also occurs at a lower level when you eat enough protein (certain amino acids are glucogenic, meaning they are metabolized similarly to carbohydrates).
Insulin works in a 4-part sequence:
- At low levels Insulin inhibits Glucagon release from the pancreas (a hormone that promotes the breakdown of stored glycogen in the liver to glucose).
- As levels increase, Insulin inhibits gluconeogenesis at the liver (the creation of glucose from free fatty acids or glucogenic amino acids).
- Then Insulin moves out into circulation and acts as an anti-catabolic agent for muscle and fat tissue (essentially it prevents break down of muscles into amino acids and adipose tissue into fatty acids).
- Finally, once levels are sufficiently high, Insulin acts to promote glucose uptake into fat and muscle cells. This is when the glucose floating around in the blood is pulled out for storage.
In low carb diets where glucose is not supplied from food sources, the body responds by switching into a state of physiological insulin resistance, or glucose sparing. It’s important to understand that this is not the same thing as the pathological insulin resistance that leads to hyperglycemia (chronically elevated blood glucose levels) and increased risk of diabetes and cardiovascular disease.
Glucose sparing (physiological insulin resistance) is generally a positive phenomenon that occurs when carbs are scarce, as in a fast or low carb diet. Certain organs and tissues prefer carbs as their main fuel source, like the brain, testes, and red blood cells. Our body has the capacity to create glucose from non-glucose fuel sources like fat and protein through a process called gluconeogenesis. When dietary sources of glucose are low, cells (mainly the muscles) that can function from non-carb sources will do so in an effort to spare this newly created glucose for the cells that require it. Hence the name glucose sparing. This physiological insulin resistance is an adaptation that allows greater resiliency in periods of food scarcity.
On the other hand, pathological Insulin resistance is a negative situation that occurs from two major pathways – widespread systemic inflammation and the unholy triad I mentioned earlier (refined carbs, excess PUFA’s, and sedentary lifestyle).
In the case of prolonged systemic inflammation, the body switches into glucose sparing mode to divert as much glucose as possible to the immune system. While this is helpful for short term infections and disease, this becomes a recipe for disaster when it comes to autoimmune disease, environmental toxin exposure, chronic stress, or metabolic dysfunction. Essentially the body is in overdrive mode, creating excess glucose to deal with a prolonged situation that is not evolutionarily consistent.
This eventually leads to weight gain, sick adipose tissue, and a self-propagating scenario where the cells become less and less responsive to insulin. Essentially, the hyperglycemia and type 2 Diabetes that can happen in response to this is an unfortunate consequence of the body’s best efforts to fight off an enemy caused by our modern diet and lifestyle.
Don’t worry, if that doesn’t quite click, I’ll break that pathway down in more detail for the second cause of pathological insulin resistance – our problematic eating patterns.
If you recall my best attempt to explain the Reactive Oxygen Species Theory of Obesity in the last part, this will build off of that. I’d highly recommend going back and reading/listening to part 3 of this series if you haven’t already. But I’ll quickly summarize the theory again here.
Fat cells are metabolized by a process called Beta Oxidation in the Mitochondrion. Because of their physical structure, saturated fats are oxidized slightly differently than unsaturated fats. Essentially, they create more Reverse Electron Transfer that results in more Reactive Oxygen Species (ROS). These ROS are an important and powerful satiety signal to the fat cells and brain. Put simply, when you digest saturated fats, you get fuller faster, are less likely to overeat, and develop insulin resistant fat cells.
Unfortunately, mainstream medicine encourages people to avoid saturated fats because they produce more ROS. While Reactive Oxygen Species do cause damage to proteins and DNA, your body has several ways to handle them easily via the oxidative stress of heat and cold, exercise, sleep, and sunlight exposure to name a few. When you consume unsaturated fats, specifically excess Poly Unsaturated Fatty Acids, you do not get this ROS production and start down the pathway of metabolic disease. We’ll touch on that in a moment.
You might be wondering why you would want Insulin resistant fat cells… Isn’t the goal to be more insulin sensitive?While insulin sensitive fat cells do pull more glucose out of the blood cells and create a short term improvement in blood glucose, this comes at the expense of long term health and function.
Only saturated fats create the Reactive Oxygen Species that signal for insulin resistant fat cells. PUFA’s don’t have this effect, meaning that the fat cells stay insulin sensitive. Remember that the third function of insulin is to prevent catabolic activity at fat and muscle cells. This means that if a fat cell is sensitive (responsive) to insulin, it will stop releasing fatty acids. It’s still absorbing glucose, but it is no longer releasing fatty acids via lipolysis. This means the fat cell is getting bigger. You don’t want that.
But if a fat cell is insulin resistant, it will continue to release fatty acids regardless of whether or not glucose is present. The fat cell is still taking up glucose, but it’s not getting bigger because the fatty acid release is matching or exceeding the uptake.
Think about it like a sink. The water is running but as long as the drain is open, everything is good. Insulin acts like the plug – if the fat cell is insulin sensitive, the plug stops the outflow of water. The sink overflows. If the fat cell is insulin resistant, the drain stays open, and water flows out.
Now, this is where things run off the rails. In the scenario where the adipose tissue (fat cells) are insulin sensitive and are not releasing fatty acids (remember, the sink is plugged up!), these fat cells get bigger and bigger. At a certain point, they “pop”. Just like the button on a pair of jeans that’s getting stretched further and further, the cell can no longer absorb more and starts to spew out fatty acids. The problem is that the fat cell is now “sick” and is also interfering with normal hormone signaling. Adipose tissue is hormonally active in that it can create signals that dictate hunger, satiety, and metabolic activity. When these cells become ill, these normal mechanisms are disrupted too.
The fatty acids that leak out of these fat cells are delivered to the liver which operates on a supply driven basis – if substrate is showing up, it needs to be dealt with! Instead of accumulating amino acids and free fatty acids, the liver converts these into glycogen or glucose (a less toxic form of energy).
Now, it’s important to remember that this is all happening in the unholy triad – generally in sedentary individuals. If the body was moving and actually burning stored glycogen, available glucose, or free fatty acids, the liver would convert these available substrates into glycogen to replace the energy that had been used. But since this isn’t happening when you’re sitting on the couch, the liver has no choice but to ship off the newly created glucose back into the blood.
So where does that glucose go? Well, it triggers even more insulin to be released from the pancreas, which directs that glucose into the fat cells. Those fat cells do their absolute best to take in more glucose, but they’re already overstuffed and keep leaking out more free fatty acids. These fatty acids go down to the liver and the cycle continues.
The death knell happens slowly as the liver starts to turn some of into fat through a process called de novo lipogenesis. This is stored in the liver as hepatic fat and eventually leads to Non-Alcoholic Fatty Liver Disease. This excess fat damages the Beta Cells of the pancreas (the cells responsible for releasing insulin), causes a lowering of HDL cholesterol, increased triglycerides, and widespread inflammation as the liver functions less and less. (And yes, this is a direct lead into cardiovascular disease, which we’ll move to in the next portion of this series.)
The entire time this is happening, you are getting fatter, your fat cells are expanding, and you are becoming more and more pathologically insulin resistant. Eventually this can result in Type 2 Diabetes onset. The higher blood glucose that diabetics experience is only partially from the diet, it’s mostly from the glucose that the liver is creating in their body. Fat cells are actually absorbing more glucose in a diabetic setting, but the leaking fatty acids from this sick tissue are forcing the liver into gluconeogenesis at an ever-greater rate. This creates a snowball effect that’s self-propagating.
Notice that I didn’t mention dietary carbs or sugar once in that? That’s because they aren’t the cause. While they certainly can play a part, the ultimate criminal that sparks this whole thing off is the excess consumption of poly unsaturated fatty acids in the presence of a caloric surplus and sedentary lifestyle. The biggest problem for refined, processed carbs is that they are highly palatable, low in nutrient density, easily trigger insulin release, and significantly increase the likelihood of a caloric surplus.
And a final note on this, the fat you eat is the fat you store. If you eat saturated fats or carbohydrates, your body will store that as saturated fats. This means that when you metabolize these fats later on, you’re using saturated fats, creating reactive oxygen species, signaling satiety, and creating insulin resistant fat cells – all good things. But when you consume PUFA’s, you store PUFA’s. This means you’ll metabolize PUFA’s for that same number of calories. And this means that you’re not creating ROS and normal adipose tissue is disrupted (i.e. you will store more fat for a given amount of calories!)
Your body cannot create PUFA’s. Therefore, the solution to preventing this situation is simple – avoid excess poly unsaturated fatty acids! These are required by the body, of course, but only in small amounts (ancestrally about 1-2% of total fat calories.) So, in practicality, the best thing you can do is to avoid any excess that doesn’t come from a naturally occurring source like eggs or meat. Generally speaking, as long as you avoid vegetable and seed oils, you’re winning the battle.
While this perfect storm of excess PUFA’s, caloric surplus from processed carbs, and sedentary lifestyle would have been close to impossible to achieve at any point in human history, it’s all too common now.
I’m sure you’re reading this and thinking “Just stop eating or go workout or something!!!” And you’re not wrong. The problem is that we don’t have the luxury of this cellular play by play as it’s happening. Additionally, we’re not all dealt an even hand genetically. Different people have different levels of tolerance for how much fat they can accumulate before becoming pathologically insulin resistant. For example, Caucasians are able to handle a significant amount of body fat before their adipose tissue become dysfunctional. People of Asian descent, on the other hand, have a much lower tolerance.
Also, because food is so emotional and easily available, it’s become far too easy to dig a hole that’s difficult to get out of. Especially when the very foods that we are told are healthy (vegetable and seed oils) are actually the root cause of this whole scenario!
So why isn’t the mainstream narrative on these PUFA’s in vegetable and seed oils changing? Great question, and unfortunately, I don’t know the answer. The reality is that most of the dietary guidelines we are given are the result of questionable epidemiological survey studies, backroom deal making, and ideological thinking that’s plant biased. These vegetable and seed oils are a replacement for the saturated fats that typically come from animal foods. Admitting that these refined oils aren’t healthy would mean supporting a narrative where animal foods are actually useful and nutritious… I’ll talk more on that in the future, but for now, just remember that there was also a time where mainstream medicine supported cigarette use as healthy.
So, if you find yourself in this downward spiral, or you at least understand that you’re not handling insulin well, what can you do?
First, understand that this process didn’t happen overnight. It will take time for your body to heal. But the good news is that in most cases, you absolutely can recover! The first step is to stop digging yourself into a hole. My recommendation is to cut out the excess PUFA’s so that your adipose tissue can start to function properly.That means absolutely no vegetable or seed oils, no corn and soy, and minimize pork and poultry that have been conventionally raised. I’d also stay away from nuts and seeds to start too. What do you replace these with? Saturated fats! You know, the type that comes naturally from animal foods…
Then, you absolutely have to get rid of the processed and refined carbohydrates. I’m talking sugars, wheat, sodas, juices, and all of the processed junk that you know shouldn’t be in your pantry. This not only removes the most insulin triggering foods from your diet, but it also will go a long way towards getting you out of the chronic caloric surplus. What do you replace this with? Real food! I’m a big fan of animal-based foods like meat, fish, and organs, but even basing your diet off of mostly vegetables and fruit would be a huge step forward.
Finally, you have to start moving. Literally, get off the couch and go for a walk. While the biggest battle is fought in the kitchen, you have to start using the stored glycogen and energy excess in your body or else you will stay stuck in the cycle of high blood sugar and overstuffed fat cells. Note that this does NOT mean you have to start crushing high intensity workouts day one. Your goal is to incorporate movement consistently throughout the day that gets your blood flowing without pushing you to exertion that will hike your hunger and lower metabolism.
While I’m sure this may sound like a lot, it’s a necessity if you want to prevent irreparable damage. And yes, this will take time. While you’ll likely start feeling much better after you bust through the cravings and desires in the first few weeks, it will take months (potentially years) for your body to fully heal and reclaim your ideal level of metabolic health. The most important part is that you stay consistent with whatever you do. Even if you “mess up”, keep showing up daily and you’ll see results eventually!
So, why do we eat so many carbs today anyways? Well, the simple answer is that they are cheap and easy to produce. While the ability to farm and produce food that is scalable and easy to store solved the problem of starvation and famine that has haunted humanity for all existence, this convenience came with its own problems. Over the years we became more efficient at harvesting these crops, developing huge swaths of land for growing one single crop, and creating pesticides that fight off insects and rodents. The pressure to make more for less stripped the soil of nutrients and ushered in the advent of genetically modified organisms resulting in an ever-increasing availability of low-quality foods.
This abundance opened the door for new scientific projects like high fructose corn syrup, vegetable and seed oils, and cheapened alternatives to real foods. In the last few hundred years, these options have slowly replaced whole foods and animal-based products that had filled our diet for the last several million years. Now, the government recommends 7-11 servings of whole grains each day as if whole wheat bread is an essential nutrient. The food pyramid has become an absurd suggestion that has led millions of people down the path of metabolic disease and insulin resistance.
Why has this plant forward ideology become the major narrative from the so-called health experts? There is a strong anti-animal bias that is pushed from proponents of a plant-based diet that use health and sustainability arguments to further their cause. At the risk of sounding conspiratorial, google “Health Foods” and tell me how much red meat you see on the image search…
The reality is that the Standard American Diet is plant based. People have cut out meat, especially red meat, at higher and higher quantities. Americans are eating their whole grains and whole wheat bread. And what has it gotten us? Close to a trillion dollars each year in spending on preventable diseases. The science and research do not back up the perspective that animal-based eating is unhealthy or a tax on the environment, regardless of how much data massaging goes into the studies.
At the end of the day, whatever diet you choose to follow is a big step forward from the usual junk food and mindless eating that most engage in. There is nothing “wrong” about a high carb diet. But that doesn’t make it an ideal eating pattern. Even if you’re one of the rare individuals who don’t suffer from food sensitivities, it’s hard to get all of your nutrition in. Point in case here is the fact that you need fat to absorb several key vitamins! If we look at our human evolution in relation to the foods we relied upon, plant foods are truly fallback foods that we consumed when animal foods weren’t available.
And if that statement offends you, I’d like to point out that our current experience with food is highly unnatural. At no point in time before now could we walk into a food store and find a full selection of vegetables and fruits available year-round. What did humans do before the miracle of worldwide transportation and monocrop agriculture?They certainly didn’t have access to mangos in Canada in the winter. This is not to say that carbs can’t play a valuable part of a whole food, nutrient dense diet, but this luxury is a modern convenience compared to our evolution as hunters and meat eaters.
So how many carbs should you eat? And what does “excess” mean? These are great questions that are best defined at the individual level. While there are many examples of individuals who eat a high carb diet from whole food based sources, I am of the opinion that carbs are best earned. If you are carrying 15 pounds or more of unwanted body fat, are sedentary, or are pathologically insulin resistant (the bad kind), then simply put, you don’t need carbohydrates. Now, before I sound too dogmatic, let me put some nuance on that.
Option 1 – High/Low Macronutrient: You can eat a high (saturated) fat, very low carb diet, OR a high carb, very low fat diet and see big improvements in your blood lipids, insulin tolerance, and overall visceral fat levels. If this is in a caloric deficit, you will achieve these health improvements while also losing weight. If this is in a caloric excess you will still gain weight (muscle if you are exercising, subcutaneous fat if you are sedentary). But from a metabolic standpoint, your body processes these high/low macronutrient diets well in that the metabolism increases to use up the excess effectively either as energy or for storage.
Please note that if the high fat diet is based predominantly off of PUFA’s, you will likely overeat and still have problems with your insulin sensitivity, visceral fat profile, and body composition. In excess these are the root problem of dysfunctional adipose tissue. And if the high carb diet is based predominantly off of processed/refined carbs, you’ll likely run into problems with inflammation in the gut, brain, and skin while also overeating and putting on significant subcutaneous fat.
The added benefit of these types of diets (and why they typically get recommended for weight loss seekers) is that by cutting down on the variety of foods you can choose from you tend to limit the total amount of calories consumed. When people have fewer options, they are less likely to overeat, leading to an easily maintained caloric deficit, leading to weight loss. This simply means that a low carb or low fat diet does nothing special for weight loss other than make it harder to overeat.
Option 2 – Mixed Macronutrient: If you are eating a balanced diet of carbs and fats, this is where you really have to be mindful of the type and amount of calories you’re eating. If kept in a caloric balance or deficit, you can have whatever ratio you’d like. But in a caloric surplus without some type of muscle engagement to actually burn off stored glycogen, you’re going to start putting on weight quickly here. Basically, you are asking your body to both metabolize and store two different types of energy sources at the same time.
In nature, carbs and fats are rarely present in the same food sources. One of the few exceptions is mammalian milk which is inherently designed to override satiation signals and help babies gain weight. In our modern world, if you’re eating excess PUFA’s, this is exacerbating the problem by creating insulin sensitive fat cells that are simply storing more PUFA’s. The glucose increase from the carbs will cause an insulin spike that shoves the blood sugar into adipose tissue while the insulin sensitive fat cells stop releasing fatty acids. This leads to inefficiency, energy crashes, cravings, and hypoglycemia. Combine this with a sedentary lifestyle that leaves adipose, muscle, and liver cells overstuffed with stored energy and you end up with the worst case scenario!
However, if the mixed macronutrient diet is built around saturated fats and whole food carbohydrates (i.e. fruits and vegetables), this is not a problem. The saturated fats create the reactive oxygen species that keep the fat cells insulin resistant (meaning that they don’t stop releasing fatty acids just because of an insulin spike). The whole food carbs are harder to overconsume since they are packaged with fiber to slow down digestion and increase satiety. This means that you’re less likely to overeat and your body can utilize these substrates efficiently without energy crashes and metabolic dysfunction.
Please keep in mind that it’s all about context! If you are lean, active, and eating real foods, you can afford occasional “splurges” of varying magnitudes. If you are metabolically broken, inflamed, overweight, and sick, you simply haven’t earned this yet. It’s no different than being in debt and wanting to buy a new car. Having nice, new things is fun, but if you don’t pay your bills off before indulging, you’re going to have bigger problems on hand.
At the end of the day, the most important decision you must make is what type of eating style is most realistic for you to stick with consistently. If you hate counting calories and struggle with moderation, then a low fat or low carb diet will likely be best. If you are more disciplined and value variety in your diet, then a mixed macronutrient diet will work well. Put plainly – No, you do not need to be on a keto/low carb diet to be healthy, lose weight, or function optimally! You also don’t have to have a starch or grain at every meal. You get to create your own eating guidelines!
Outside of calories, you also have to factor in nutrient density and bioavailability (i.e. getting the vitamins and minerals you need). While high carb diets can work, my fear is that you won’t get enough of the fats required to actually absorb many of those nutrients, like the fat soluble vitamins A, D, E, and K. When it comes down to it, my recommendation for overall health, weight loss, and healing is an animal based, low carb, high fat eating style for simplicity, nutrient density, and satiety. But you probably already knew that!
Another note of importance is that insulin is not a bad thing! While striving for mostly consistent blood glucose and insulin levels is a good goal, living life through the lens of “avoid insulin spikes at all times” is not healthy or necessary. Ideally, you’re able to enjoy sweet treats like ice cream or a pizza in moderation in life! When you eat these, a healthy response is a sharp insulin spike that clears out excess blood glucose and then goes away over the span of an hour or less. This is your body’s built-in mechanism for managing sugar.
*If you are interested in really diving deep into your health, the absolute BEST thing you can do is get a continuous glucose monitor to wear for a 2-4 week period. This allows you to track your blood glucose in real time as you respond to meals, sleep, exercise, and cold showers. For example, I learned that a 15 second cold shower has a dramatic response on lowering my blood glucose over the rest of the day! Nutrisense is my recommended company for this. The information and service you receive makes this a no brainer and a bargain. I cannot encourage this decision enough!
The issue happens when you make a habit out of these insulinogenic foods. While all carbs get broken down to the same substrates, the refined/processed carbs do so much more quickly than whole food carbohydrates. Many of these have been created in a lab to highjack your satiety and craving mechanisms. Outside of the impact that this repetitive insulin spike has, these foods are really problematic for your gut and digestion, cause inflammation in the brain, and have a negative impact on blood pressure and cardiovascular endothelial function (Stuff we’ll talk about in a future section).
Finally, I’ll wrap this up with the most important take home notes. Carb “addiction” is a real thing for many people. While the brain might not structurally change, the insulin spike mitigates cortisol in the body and functions as a natural stress reliever. That’s why the late-night sweet tooth or glass of wine is such a hard habit to kick. Ultimately, if you really want to lose weight or optimize your health, you must incorporate lifestyle changes. You have to address the stressors in your life. You have to get better sleep. You have to get more nutrient dense foods in your diet. The easiest way to start this is to cut out corn, wheat, soy, processed sugars, and vegetable/seed oils. If you do that in the context of adding activity to your daily routine (start with small walks), you are well on your way to a brighter future of vitality and optimal health! And yes, while these changes are not easy, it truly is that simple.
Read part 5 here, all about cholesterol and cardiovascular disease.
