Tuesday, April 26, 2022

Your Digestive Tract and your Nervous System

 Your Digestive Tract and your Nervous System:


This week we are going to discuss the digestive tract, how it works with your microbiome, and your nervous system.


Starting at the beginning of your digestive tract your mouth provides accommodation to hundreds of species of bacteria, including a fairly rough crowd of Streptococcus and Staphylococcus, bacteria known to cause disease. In a healthy person these are generally not troublesome, being held in check by other bacteria. In a person with gut dysbiosis the bad bacteria are no longer in check causing sugar cravings, which will create short term bliss, but long term sugar centered microbiota can potentially make you anxious and depressed. Jumping back to your mouth, we have home-brewed antibiotics in there! This is a part of your innate immune system, and many pathogens are immediately killed right here in your mouth thanks to the copious flows of saliva. Another system in your body is called the enteric nervous system (ENS)—the gut’s nervous system, which is large and complex enough to be called the second brain. We’ll talk more about that in a bit. Did you know people with anxiety are three times more likely to have GERD, so from a psychobiotic point of view, this connection to mental health is important. Going back to your GI tract as food and the microbes that come with it travel down your esophagus they enter the stomach where most species die. Only a select group of microbes, including Candida, Helicobacter, and Lactobacillus species, can handle the acidity in your stomach. This points to a problem not just with psychobiotics, but also with probiotics in general: Each species can have quite different effects, and those effects may even change with their surroundings. When it comes to microbes, easy answers are elusive. From the time you start to eat solid food, you develop a core set of bacteria that may stay with you for life—or at least until you take antibiotics and kill them off. Even then, many microbes in your custom microbiota will usually return because they are able to hide deep in the crypts of your intestines. The standard American low-fiber diet, coupled with a steady drumbeat of antibiotic treatments, has come close to wiping out certain bacterial species in the Western world. It is possible that we are driving some microbial species to extinction. If some of these have psychobiotic properties, we could be affecting our collective mood without realizing it. The disappearance of beneficial microbes could, in fact, be a major contributor to the alarming rise in anxiety and depression seen around the world. But fiber is manna for the microbes living in your large intestine, and they squeeze out a surprising amount of useful fuel that can then be absorbed by your gut. Both Crohn’s and UC involve inflammation, which is often associated with anxiety and depression, highlighting a gut-brain connection. Moving down the GI tract to your colon. The extra size of your colon means that there is plenty of time and room for the chyme to slowly inch by, bubbling and fermenting as it goes. This is the source of flatulence, which is actually a sign of a properly functioning microbiota. Your colon pampers the bacteria that produce vitamins that humans cannot normally synthesize. Bifido, Lacto, and Propionibacteria can all produce B vitamins, including B12, thiamine, riboflavin, niacin, biotin, and folic acid. A shortage of these vitamins can lead to depression, so here is yet another major psychobiotic contribution made by these microbes in your large intestine. And that’s not all: Bacteria like E. coli help produce various forms of vitamin K, important in blood clotting. You can find it in green vegetables, but the bacteria in your gut make the bulk of what you use. Babies without a good bacterial system in place may not be able to get enough vitamin K, and it is common to give newborns a shot of it to get them started. There is also some evidence that vitamin K can reduce anxiety. The fact is: Your bacteria naturally produce neurotransmitters in a volume that rivals that provided by prescription drugs. For instance, Lacto and Bifido, two of the bacteria genera abundant in your colon, both produce GABA (gamma aminobutyric acid), a key neurotransmitter that can have a tranquilizing effect, dialing down your anxiety. In the colon, Streptococcus and Escherichia species produce serotonin—the “happiness” neurotransmitter that is an important player in mood and provides the guiding rationale for selective serotonin reuptake inhibitors (SSRIs), a class of drugs designed to maintain serotonin levels in the body and now the most popular type of drug prescribed for mood disorders. Some 90 percent of the body’s serotonin is found in the gut. That’s because your gut—the second brain —uses the same neuroactive chemicals to compute and process information as the first brain does. Accumulating data now indicate that the gut microbiota communicates with the central nervous system (CNS) through neural, immune, and endocrine pathways—and thereby influences brain function and behavior. There are three main communication channels between your brain and your gut: your nervous system, your immune system, and your endocrine system. The circulatory and lymphatic systems also play supporting roles, but these first three are dominant. The nervous system relays information to and throughout your brain. It communicates using chemicals called neurotransmitters. Its communication style is fast and point to point, but short-acting. The immune system is at the ready to rally a defensive response against threats to healthy homeostasis. It uses the protein molecules called cytokines to signal distress. It can communicate quickly, but its urgent chemical effect can be harsh enough to cause tissue damage. The endocrine system monitors and manages growth and metabolism. Its component glands communicate by secreting hormones into your blood and thus sending signals throughout the body. Its operations are slower, more moderate and systemic, but longer-acting than those of the other two systems. The nervous system has two major divisions: the central nervous system (CNS), composed of the brain and spine, and the peripheral nervous system, less well known but just as important. The peripheral nervous system divides into four parts: somatic, sympathetic, parasympathetic, and enteric. To achieve optimal gut-brain health, all four parts are operative, in balance, and in communication with one another and with the CNS. You use the somatic nervous system whenever you voluntarily do anything. In the context of psychobiotics, the somatic system matters because you maintain voluntary control over what you eat (or don’t eat)—and thus, you exert some nervous system control over your microbiota. The sympathetic nervous system is the part often nicknamed “fight or flight.” when it’s activated, in other words, all other systems get put on the back burner. The stresses that activate this system can be external—or internal—tension held in muscles or, pertinent to psychobiotics, food habits that trigger continued inflammation in the gut. The parasympathetic nervous system has a nickname, too: “feed and breed.” When the parasympathetic nervous system is chugging along, you achieve a state of health, happiness, and balance we all strive for. The enteric nervous system is the one that operates in your gut, your second brain. This system, including your microbiota, holds the keys to dismantling any chronic stress responses you may be experiencing, and to returning your body to a healthy homeostasis. All three of these systems operate on autopilot, so typically you don’t even think about them.


Tuesday, April 19, 2022

Gut Dysbiosis and the Microbiota Throughout Your Life

 Gut Dysbiosis and the Microbiota Throughout Your Life: 


This week we are diving deeper into your gut microbiota throughout your life and gut dysbiosis which we touched on last week. 


Your microbiota is as unique to you as your fingerprints. This is why it’s unlikely that any single probiotic or psychobiotic will work for everyone. You will need to experiment to see what works best for you. There are 100 trillion bacteria in your gut, composed of at least 500 species. The bulk of them, some 98 percent, come from about 40 species divided into just four big groups (phyla). The two main groups are Lactobacillus and Bifidobacteria. Gut microbes produce all manner of chemicals to talk with each other and to your gut; that information is relayed to your brain primarily via the vagus nerve, which is a long wandering nerve from the brain to all your bodily organs. The problem with this communication is that it has very few words. It’s mostly “okay, okay, okay, hungry, hungry, full, okay, okay…”. Here’s an example of how that works. Some microbes, especially our friendly Bifido species, produce butyrate, which feeds and heals the lining of your gut. Butyrate can make its way to the brain, where it can induce a good mood, dampen inflammation, or encourage the production of a brain-growth hormone. All these changes can improve your mood and even help you to think better. Sugar cravings can be seen as a consequence of a dysbiotic gut. That is likely related to the sugar cravings of people in mental hospitals. Sugar cravings have also been seen in people who are stressed. These are pathogens, but the same principles seem to apply to commensal bacteria as well. If they don’t get what they want, they can make a fuss. When that happens, you may not know it directly, but they have ways of making you uncomfortable until you give them what they want. It’s that funky feeling that makes you suddenly crave a candy bar or other snack. You may not know why, but you know there is a bonbon-size hole in your gut, and it quickly becomes your job to fill it. If your gut is healthy, there will be a cosmopolitan bustle of microbes with no one species dominating. That means that no one species can exert too much control. A dysbiotic gut, on the other hand, has less diversity. Let’s look at a dysbiotic gut through life starting with mom and baby. A dysbiotic gut may not respond properly to the estrogen, which can lead to problems down the road for both mother and child. Meanwhile, at this stage of pregnancy, your mother’s gut microbiota is changing to accommodate feeding you. Remarkably, these changes look a lot like metabolic syndrome, a kind of prediabetes, inducing weight gain and insulin resistance. Between the first and third trimester, the number of bacterial species drops and those that remain seem to favor putting on fat. This means that there must be some kind of mechanism that prods the gut microbiota toward extracting extra energy from food to take care of you. The same mechanism, triggered at the wrong time, could lead to obesity, gut dysbiosis, and even type 2 diabetes. You are swathed in this bacterial blanket before you ever poke your head out of the womb. Unless you get violently ill or end up on an antibiotic regimen in the first days of your existence, your body will form a memory of this first bacterial initiation that will likely last for the rest of your life. This bacterial appetizer is there, among other reasons, to teach your immune system what to expect. If you were born by cesarean, you missed a lot of that messy stuff. Instead, you were whisked away to a nursery where you picked up a bacterial population unique to your nurse’s skin and your hospital. Some studies have shown that children delivered by C-section may lack important Bacteroides species for up to the first 18 months of life, making them more likely to suffer from asthma and allergies. New studies suggest that babies born by C-section react differently to stress, and may even be more susceptible to depression and anxiety—all hypothetically correlated to gut and microbiota health. Not all studies are so downbeat, though: New research has shown that at around six weeks, the microbiota of most of these children has normalized, with some of that due to breast-feeding. Jumping quick to why having bacteria is good and that includes a balance of both the good and the bad. If you grew up or choose to now live in a germ free environment you may have some differences in your brain. Studies have also shown that a germ-free mouse may have an unusual hippocampus, a seahorse-shaped part of the brain that is involved with both memory and emotion, and amygdala. We noted some dramatic changes in nerve cells, including different kinds and shapes of neurons as well as the growth of more new nerve cells than in normal mice. Somehow, the microbiota is controlling the growth of important memory and anxiety centers of the brain. We have also demonstrated that extra myelin is formed in the brains of germ-free mice. We found that myelination—especially in a region of the brain known as the prefrontal cortex —is regulated by the microbiome. The prefrontal cortex is an important area for top-down regulation of the stress response and is involved with depression and schizophrenia. We found that these changes could be reversed by providing the mice with a conventional microbiota after weaning, suggesting that the microbiota is a potential target for myelin-based psychiatric disorders. This observation, which came to be called the hygiene hypothesis, implies that cleanliness actually has a negative influence on normal development, and it has had a big impact on how people look at bacteria. Rather than being pathogenic or at best marginally useful, a certain set of bacteria may actually be essential for the proper development of your body’s defenses. It is the job of these microbes to train your immune system, and without them, your system stays naive and prone to overreaction.

Remember bacteria are important! Back to mom and baby let’s look at breastmilk. Breastmilk is both a prebiotic and probiotic drink—a combination of microbes and the food microbes want—a sort of homemade kefir. These prebiotics not only feed the starter microbiota, they also reduce the release of the stress hormone cortisol, keeping you happy and content. The first milk, produced right after delivery, is called colostrum and is packed with hundreds of species of bacteria. It is also full of maternal white blood cells and antibodies to establish a newborn’s foundational immune system—kind of an immune system transplant, designed to provide instant protection for your defenseless body. For such an innocuous-looking substance, milk packs an astounding immunological punch. The milk is filled with regulatory cells called T-regs. They are important players in the baroque world of immunity. As a baby, your thymus is highly active while you build up your unique collection of antibodies and T-regs. As you get older, your thymus shrivels, and you might find it harder to fight off pathogens. That can lead to chronic inflammation and depression as you age. After around six months of breast-feeding, the bacteria in your mother’s milk start to change. Instead of bacteria that are expert at digesting milk sugars, the new milk microbiota starts to look a lot like your mother’s own oral bacteria. This transformation helps prepare you for solid food, because a lot of the work of digestion starts in the mouth. Mucus in the gut comes in multiple formulations. First a network of sugary strands stuck tight to the enterocytes provides an excellent physical barrier against microbes. On top of that is a second, less dense mucus layer full of a microbial buffet of sugars. Embedded in this second mucus layer is your most important defense against pathogens: other bacteria. During the early years of your life, your immune system needs to be educated to leave these protective bacteria alone. If your immune system kills your guardian bacteria, pathogens can directly attack your gut. They can eat holes in your gut lining, letting bacteria into your bloodstream and provoking a systemic immune response. Although the basic framework of your microbiota is set by age two, it is still a dynamic situation. As you grow, there will still be changes, and there is an overall drift away from Bifido species. Teenage diets, typically laughable, lead to a rash of gut problems. And stress affects the teenage brain and microbiota alike. There’s good news and bad: You can make a difference, because this may be the last time in your life that you can make durable changes to your microbiota. But if a bad set of microbes gets established, you may have to fight for the rest of your life to keep the upper hand. It’s never too late: A good diet can keep your gut happy, increase your health span, and improve your mood, all at the same time. 


Tuesday, April 12, 2022

Intro to Gut Health: The Psychobiotic Revolution

 Intro to Gut Health: The Psychobiotic Revolution by John F. Cryan, Scott C. Anderson, and Ted Dinan


This week we will discuss the intro to the book “The Psychobiotic Revolution”. This book really dives into the gut flora and fauna and how to keep them happy and working properly to avoid disease, improve mental health, and to aid in better digestion. 


Let’s talk about your gut microbiota. A single bacterium, given enough to eat, could multiply until its brethren reached the mass of Earth in just two days. That’s a big clue to their superpower: They are excellent at reproduction. They are also profligate interbreeders and think nothing of swapping genes with whoever is nearby. In your gut today, you are host to trillions of bacteria. They are online 24/7, duking it out with rogue microbes and even helping you nutritionally by producing vitamins and eking out the last few calories from every speck of fiber. The community of microbes living in your gut—your so-called microbiota—is not just made of bacteria. Your microbiota is also home to ancient life-forms related to the colorful creatures that tint hot springs, called Archaea. It includes the kings of fermentation, the yeasts. It hosts swimming single celled protozoans, constantly on the prowl. It also includes an even more insane number of viruses. Your gut microbiota is spectacularly cosmopolitan, making it a challenging beast to study. Your microbiota communicates directly with the second brain. Your second brain is the network of nerves surrounding your gut. A good set of microbes encourages this second brain to keep the feast moving. For good health, including mental health, the food you eat needs to be good for you and for your microbiota. In 2013, we defined a psychobiotic as a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness. As a class of probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act on the brain-gut axis. Preclinical evaluation in rodents suggests that certain psychobiotics possess antidepressant or anxiety-reducing activity. Your microbiota can make you feel better if you feed it what it wants, and it can make you feel miserable if you don’t. One way is through cravings. You may feel that you just have a personal penchant for certain candies, but it might not be up to you at all. Your cravings, it seems, might belong more to the second brain in your gut than the one in your head. Your microbiota can affect your mood as well. For example let’s look at food poisoning: your microbiota recognizes the pathogenic intruders and starts to attack them. It tries starving and poisoning them and —importantly—it alerts your immune system. Now kicked into high gear, your second brain prepares to purge your system. Your mood at that point is acute anxiety. Now imagine that happening day after day. That’s what occurs when you have chronic inflammation, often caused by a breach in your microbiotic defenses. Anxiety and depression can become a constant companion. The microbiota is renewed every hour or so. The turnover is huge, and you may be able to divert it with some surprisingly easy tricks. But the gut-brain connection is a two-way street. Despair, anxiety, and depression can lead to negative changes to your microbiota, called dysbiosis. That disruption can channel anxiety and depression right back into your brain. It creates what most of life tries its best to avoid: a positive feedback loop, otherwise known as a vicious cycle. Research continues to reveal connections between gut health and other diseases, both mental and physical. Depression accompanies many of these diseases, including Parkinson’s, Alzheimer’s, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), obesity, psoriasis, arthritis, multiple sclerosis (MS), autism, and many more. These diseases sometimes start with depression or anxiety—and sometimes they end with them. Your immune system can detect these bacterial molecules at very low levels. This is part of your innate immune system, and it doesn’t require any training. It just reacts, and it does so with alacrity. But you have another immune system that is more subtle and that requires training: Your adaptive immune system is deliriously complex. This adaptive system—working closely with your microbiota—can protect you against pathogens that it has never seen before. A microbiota that is unbalanced and that provokes an immune response is called dysbiotic. It can lead to inflammation, which is a significant contributor to depression and anxiety. Worse yet, it is a major predictor of mental decline, making dysbiosis important to everyone, regardless of mood. Depression is associated with brain atrophy. So your depression is not only setting you back today, but could have even worse long-term effects. The gut has its own nervous system, independent of the central nervous system. It isn’t organized in a lump like the brain but rather as an intricate double-layered lacework surrounding your entire gut like a tube sock. You have your own homegrown microbes that are friendly. These are your commensals, from Latin, meaning “together at the table.” If these friendly microbes also keep your mood on an even keel, they are called psychobiotics. Astonishingly, your microbes themselves can talk to both brains using chemicals similar to neurotransmitters (the communication molecules of your brain) and other molecules like hormones, fatty acids, metabolites, and cytokines. This is because the gut is a highly specialized tissue whose challenging job is to suck nutrition out of food without also sucking in pathogens. If pathogens leak through the lining and get out of your gut, your immune cells will follow them into your blood system and spark a systemic inflammation—a condition often called leaky gut. When your gut is out of whack you may get body signals like we explained in the food poisoning example which is called sickness behavior, and it has a lot in common with depression. When it comes to your digestive tract, most of it we cannot feel. You can move your tongue and swallow at the near end, and you can control your sphincter at the far end. Everything in between is pretty much out of your control. That’s one less thing you need to worry about, which is always welcome, but it eliminates a lot of important inside information. Without definitive cues from your gut, you often have to guess what’s wrong with you. If you just feel a general malaise, you may not place the source of your worries where it often belongs: in your gut. The microbiota, they found, plays an important role in the formation of stress circuits. But most antibiotics are broad-spectrum, killing a wide variety of microbes. As long as you think all bacteria are bad, that scorched-earth treatment sounds great. But it turns out that most bacteria are not bad. In fact, your good bacteria rival your own immune system when it comes to killing pathogens. Indiscriminate dosing can damage friendly microbes—and we’re only now realizing how great that damage can be. Yeasts are notorious for stepping in when commensal bacteria are knocked down. Candida is a yeast that loves the intestinal environment. Under siege by Candida, your gut may become poked with holes and start to leak food bits into your bloodstream. Your immune system may then attack the out-of-place food particles, in the process setting up food allergies, which are often linked to anxiety and depression. It is not uncommon to have allergies disappear when yeast infections are cleared up. In the lab, the researchers collected fecal samples from 34 depressed human patients and 33 healthy controls. They found that the microbiota of the patients with depression was less diverse than the controls. They then transferred these samples to rats. The rats that received fecal matter from depressed patients showed symptoms of depression and anxiety, while the controls did not. This suggested to us that the microbiota may play a causal role in the development of depression, and might present a target for treatment and prevention of this disorder. If your immune system is continuously on alert, you’ll develop chronic inflammation, which can lead to depression and anxiety.


Tuesday, April 5, 2022

Obesity and the Regulation of Weight: The Final Part

 In our final blog edition of Good Calories, Bad Calories we are going to discuss how your hormones play a role in obesity, more on carbs and sugar, and the main takeaways from the book.


Hormones:

Common obesity is the only manifestation of an endocrine disturbance, so slight that it upsets the balance of intake and output by less than .1 of 1%. Neither eating less or exercising more will lead to long term weight loss as the body naturally compensates. We get hungry and if we can’t satisfy that hunger we’ll get lethargic and our metabolism will slow down to balance our intake. This happens whether we are lean or obese. As food intake drops, the level of thyroid hormone falls and metabolic rate is lowered. Food intake has to be reduced even further to drop below the level of energy expenditure. Hunger mechanisms, including the feeling of an empty stomach lead us to search for food. Obesity may be caused by a hormonal or metabolic defect determined primarily by genetic inheritance but the epidemiology tells us that this defect is triggered by environmental factors. The likely explanation is the effect of diet on this regulation of fat metabolism and energy balance. Since insulin is the hormone responsible for promoting the incorporation of fat into our adipose tissue and the conversion of carbs into fat, the obvious suspects are refined carbs and easily digestible starches which have well documented effects on insulin. In obesity, the cause is an excess of insulin or an inordinate sensitivity to insulin by the fat cells; the result is an overstock of fuel in the adipose tissue and so internal starvation but now the symptoms are weight gain and hunger. Insulin seemed to have a dramatic effect on hunger, that insulin was the primary regulator of fat deposition in the adipose tissue, and that obese patients had chronically high levels of insulin. Other hormones such as adrenaline have been shown to increase the mobilization of fat from the fat cells. Virtually anything that increases the secretion of insulin will also suppress the secretion of hormones that release fat from the fat tissue. Sex hormones determine where fat is stored as evidence by the differences in fat distribution between men and women. Thyroid hormones, adrenaline, and growth hormone accelerate the release of fatty acids from fat depots, as does a hormone known as glucagon, secreted by the pancreas. Female sex hormones do not appear to play a major role in determining where fat appears on the body, women who have their ovaries removed put on fat very much like other women. These hormones do however seem to affect the quantity of fat which would explain the tendency of women to gain weight after menopause. The hormones that promote fat mobilization include: epinephrine, norepinephrine, ACTH, glucagon, TSH, Melanocyte stimulating hormone, vasopressin, and GH;  the hormones that promote fat accumulation include: insulin.


Carbs and Sugar:

Though the obese did not appear to eat more calories on average than the lean they did consume more carbs. There is something about carbs that allows the consumption of such enormous quantities of food and yet still induces hunger as the night approaches. The implication is that there is a direct connection between carbs and our experience of hunger, or between fat and protein and our experience of satiety. In early weight loss diets only a minimal amount of carbs and added fats would be allowed in the diet due to being considered nonessential. The idea was to keep the body in what is called nitrogen equilibrium. Though glucose is a primary fuel for the brain it’s not the only fuel, the body can also use ketones produced in the liver the rest come from glucose synthesized from the amino acids in protein either from the diet or from the breakdown of muscle. This suggested another way of defining a balanced diet, it’s possible that eating easily digestible carbs and sugars increases our need for vitamins that we would otherwise derive from animal products in sufficient quantities. The uptake of vitamin C by cells is globally inhibited when blood sugar levels are elevated. In every case the weight loss after 3-6 months was 2-3x greater on the low carb unrestricted calorie than calorie restricted low fat. Four facts had been established beyond a reasonable doubt: 1. Carbs are singularly responsible for prompting insulin secretion, 2. Insulin is singularly responsible for inducing fat accumulation, 3. Dietary carbs are required for excess fat accumulation, 4. Both type 2 diabetes and obese have abnormally elevated levels of circulating insulin and a greatly exaggerated insulin response to carbs in the diet. Just a few more details are necessary to understand why we get fat. The first is that the amount of glycerol phosphate available to the fat cells to accumulate fat to bind the fatty acids together into triglycerides and lock them into adipose tissue also depends directly on the carbs in the diet. Dietary glucose is the primary source of glycerol phosphate. It may be impossible to store excess body fat without at least some carbs in the diet and without ongoing metabolism of these dietary carbs to provide glucose and the necessary glycerol phosphate. The storage of fat and therefore the production and maintenance of obesity cannot take place unless glucose is being metabolized. Fructose is converted more efficiently into glycerol phosphate than glucose. Fructose is considered the most lipogenic carb. However it does not stimulate the pancreas to produce insulin so glucose is still needed. The 50/50 glucose/fructose table sugar or HFCS does this. The longer the insulin remains elevated the longer the fat cells will accumulate fat and the longer they’ll go without releasing it. There is great biological variation in what they called the insulin-secretory responses. This causes us to secrete more or less insulin to the same amount of carb ingested, could be more or less effective at lowering blood sugar or at promoting fat accumulation, or it remains elevated in the circulation for longer or shorter periods of time. And because variations of less than 1% in the partitioning of calories either for fuel or for storage as fat could lead to the accumulation of tens of pounds of excess fat over over a decade it would take only infinitesimal variations in these insulin-secretory responses to mark the difference between leanness and obesity, between health and diabetes. We can also talk about the supply of nutrients from mom to baby. The nutrient supply from mother to developing child passes the placenta in proportion to the nutrient concentration in the mother’s bloodstream. If the mother has high blood sugar then the developing pancreas in the fetus will respond to this stimulus by overproducing insulin secreting cells. It suggests that once a generation of adolescents and adults start eating the highly refined carbs and sugars now ubiquitous in our diets even their children will feel the effect and perhaps their children’s children.


Main Takeaways:

  1. Dietary fat, whether saturated or not, is not a cause of obesity, heart disease, or any other chronic disease of civilization.

  2. The problem is the carbs in the diet, their effect on insulin secretion, and thus hormonal regulation of homeostasis, the more easily digestible and refined the carb the greater the effect on our health, weight, and well-being.

  3. Sugars, sucrose and HFCS are harmful, because the combination of fructose and glucose simultaneously elevates insulin levels while overloading the liver with carbs.

  4. Through their direct effect on insulin and blood sugar, refined carbs, starches, sugars are the dietary cause of coronary heart disease and diabetes. They are most likely the dietary causes of cancer, Alzheimer's, and other chronic diseases of civilization.

  5. Obesity is a disorder of excess fat accumulation, not overeating, and not sedentary behavior.

  6. Consuming excess calories does not cause us to grow fatter anymore than it causes a child to grow taller. Expanding more energy than we consume does not lead to long-term weight loss, it leads to hunger.

  7. Fattening and obesity are caused by an imbalance in the hormone regulation of adipose tissue and fat metabolism. Fat synthesis and storage exceed the mobilization of fat from the adipose tissue and its subsequent oxidation. We become leaner when the hormonal regulation of the fat tissue reverses this balance.

  8. Insulin is the primary regulator of fat storage. When insulin levels are elevated, either chronically or after a meal, we accumulate fat in our fat tissue. When insulin falls we release fat from our fat tissue and use it for fuel.

  9. By stimulating insulin secretion, carbs make us fat and ultimately cause obesity. The fewer the carbs we consume the leaner we will be.

  10. By driving fat accumulation, carbs also increase hunger and decrease the amo9unt of energy we expend in metabolism and physical activity.

  11. Evolution should be our best guide for what constitutes a healthy diet. It takes time for a population or a species to adapt to any new factor in its environment; the longer we’ve been eating a particular food as a species, and the closer that food is to its natural state the less harm it is likely to do.

  12. The most dramatic alterations in human diets in the past 2 million years are 1. The transition from carb poor to carb rich diets that came with the invention of agriculture, 2. The increasing refinement of those carbs, 3. The dramatic increases in fructose consumption.

  13. Can take the necessary steps to prevent these disorders rather than trying to cure them or ameliorate them after the fact.

  14. We don’t get fat because we’re sedentary, we become sedentary because we’re getting fat. And we’re not lean because we’re active, rather we’re active because we’re lean and our bodies are predisposed to burn off the calories we consume rather than stash them away in our fat tissue.