It’s really good!
I took pretty detailed notes as I was reading, so I thought I would share them in case anyone finds it useful. (I also added a much shorter summary to my book list.)
The main theme of Why We Get Sick is how something called “insulin resistance” (IR) underlies most chronic diseases, including diabetes, heart disease, and many others.
Dr Bikman not only clearly explains what IR is, he also presents a comprehensive and evidence-based plan for combating it.
If you’ve never heard of insulin resistance, you’re not alone. Most people haven’t.
It’s super-common though, affecting well over half of American adults. So it’s probably worth understanding, at least a little bit. 😉
Here’s the simple explanation:
IR means the hormone called insulin doesn’t work as well as it used to, so your pancreas has to make more and more of it to get the job done.
Why does that matter?
Having high insulin makes you more likely to suffer from high blood pressure, kidney failure, diabetes, cancer, dementia, infertility, heart disease, and many other health problems.
But if you understand what causes IR, and how to fix it…you’ll have a better chance of avoiding those diseases and living a healthy, productive life.
(Spoiler alert: The solution to IR includes things like physical activity, cutting out processed carbs, and fasting.)
So check out the book. But in the meantime, feel free to see what you can learn from these notes.
I used some jargon and abbreviations, so certain parts will be easier to understand if you have a medical background. I think you can still get the main points in most cases though.
The notes are also pretty long. But don’t worry…not as long as the actual book (haha). And I used bullet points to make them a little easier to peruse.
Without further ado.
Dr Jason Fung talks about the connection between his clinical observations (about fasting, low carb etc.) and Dr Bikman’s research. Basically, they’re both looking at insulin resistance, but from a different perspective.
Dr Bikman talks about his journey. Gradually discovering that insulin resistance causes or contributes to nearly every chronic disease. Over 80% of American adults may have it. It’s rampant in many other countries as well.
Part I: The Problem: What is insulin resistance and why does it matter?
Chapter 1 – What is Insulin Resistance (IR)?
- Insulin has effects in basically every organ.
- Insulin resistance (IR) means insulin doesn’t work as well and you have to make more of it.
- IR is extremely common, at least half of American adults have it, and possibly more like 88%. It’s also very common in other developed nations.
- IR is a better marker for (and description of) type 2 diabetes than high blood sugar.
- Diabetes is glucose-centric because of the ease of measuring blood sugar, and the more observable symptoms of hyperglycemia (like sweet urine).
- High insulin predates type 2 diabetes by up to 20 years.
Chapter 2 – Heart Health
- IR causes heart disease through various mechanisms.
- Insulin increases aldosterone, which increases blood pressure.
- IR stimulates growth of endothelium.
- Initially increases NO, but later becomes resistant.
- Activates sympathetic nervous system.
- Increases production of small dense LDL.
- (Related: TG/HDL < 2.0 is a good sign for LDL particle size. Statins increase the ratio of small / big LDL, which is bad.)
- Insulin increases oxidative stress, and vice versa.
- (Linoleic acid easily oxidized.)
- Normal levels of insulin reduce inflammation, but excess / resistance increases inflammation.
- Altogether, high insulin promotes atherosclerosis and blockages.
- Also associated with cardiomyopathy, especially dilated (probably due to poor glucose uptake), and also hypertrophic (probably due to excess growth promotion).
- No single factor more strongly associated with CVD than IR.
Chapter 3 – The Brain and Neurological Disorders
- IR is associated with various neurologic diseases.
- After apoE4, IR has the strongest connection with Alzheimer’s, even more than age.
- Probably due to IR in the brain, leading to inadequate glucose uptake and energy problems.
- Vascular dementia is affected by vascular mechanisms in previous chapter.
- IR is associated with Parkinson’s and vice versa – dopamine lowering medications cause IR temporarily.
- Migraines have a strong association as well, possibly due to glucose uptake issues.
- Same for peripheral neuropathy.
Chapter 4 – Reproductive Health
- IR is associated with reproductive problems in men and women, and puberty disturbance in youth.
- IR is normal in pregnancy, but gets out of control in gestational diabetes (& GD 7x more likely to get DM2). It’s a fine line.
- Preeclampsia has a strong association with IR also, probably because IR increases BP in various ways (see ch. 2).
- IR in pregnancy leads to oversized babies, 40% more likely to become obese as teens.
- Oddly, undernourished babies are also more likely to become obese (like in the Dutch famine study).
- The father’s health matters too.
- PCOS results from IR preventing estrogen release from ovaries, androgen conversion to estrogen, and probably LH in brain as well. So hormones are not moving as normal, and one egg does not become dominant (hence multiple ovarian cysts).
- Lower insulin means clomiphene is more likely to work. Female infertility often reverses if IR is corrected.
- In men, IR contributes to lower testosterone, sperm dysfunction, and ED.
- Body fat produces aromatase, converting testosterone to estrogen.
- Lower testosterone contributes to fewer sperm, or poorly functioning sperm.
- Lower testosterone and vascular effects of IR contribute to ED.
- IR is probably also a major contributor to earlier and earlier puberty, as fat storage and leptin send signals to start puberty.
Chapter 5 – Cancer
- Out-of-control growth, Warburg effect.
- Breast, prostate, and colon have strong associations with insulin.
- Breast cancer has 6x as many insulin receptors, the prostate is similar. (BPH also 2-3x more likely with IR.)
- Colorectal cancer 2-3x more likely with IR. Cancer is also random, but changing what we can control is a rational approach.
Chapter 6 – Aging, the Skin, Muscles, and Bones
- IR associated with various skin problems, including acanthosis nigricans, acne, and psoriasis.
- Strong association with Ménière’s disease, tinnitus, and hearing loss as well.
- IR negatively impacts muscle growth and maintenance.
- Fibromyalgia association.
- Bones tend to be more brittle, have more fractures.
- Chondrocytes and synovial cells are also affected and don’t produce cartilage or synovial fluid as effectively.
- Glucosamine seems to cause IR.
- Kidneys retain more uric acid in gout patients.
Chapter 7 – GI & Kidney Health
- IR contributes directly and indirectly to GERD & gastroparesis.
- Liver: IR promotes hyperlipidemia and hyperglycemia.
- It also contributes to fatty liver, which is worsened by fructose, including fruit juice (in children and adults).
- Eating your fruit is not nearly as bad as drinking it.
- Fatty liver is very common now, about ⅓ of adults, and leads to liver failure.
- IR also makes Hep. C get worse more quickly.
- IR contributes to gallstones directly, and also slows gallbladder emptying.
- (A low-fat diet also slows gallbladder emptying, making things worse).
- Kidneys: IR makes kidney stones more likely by stimulating PTH to raise calcium, and also making the urine more alkaline.
- IR is also associated with kidney failure, indirectly (HTN, high BG, etc) and perhaps directly as well.
- ESRD patients are much more likely to die in general, so it would be worth measuring insulin to catch this earlier.
Part II: Causes: What makes us insulin resistant in the first place?
Chapter 8 – Metabolic Syndrome & Obesity
- ⅓ of adults now have metabolic syndrome, so it’s getting more press.
- IR is not only one of the criteria, but a major contributor to the other features.
- There is typically no insulin shortage in people with type 2 diabetes. Giving them more insulin is nonsense, and makes them gain more weight and become more insulin resistant.
- Obesity and insulin are kind of a chicken/egg argument. IR probably precedes obesity more often than not, but there is a threshold beyond which people stop becoming more obese just from insulin.
- Leptin normally reduces insulin secretion (and insulin stimulates leptin), but people tend to be leptin resistant now.
- If you eat the same number of calories but have more insulin, you’ll get fatter. This is evident with diabetic patients and certain types of diets.
- There was an understanding of hormones’ influence on obesity in early 1900s, but starting in mid 1900s the “calories in calories out” dogma started catching on. This approach is oversimplified and ignores the roles of hormones in weight gain, insulin chief among them.
Chapter 9 – How Age & Genetics Influence Insulin
- Let’s start by talking about the things we can’t control, and hopefully get more motivated to take care of the things we can control.
- IR tends to increase with age, including postmenopausal with lower estrogen, as well as lower testosterone.
- IR is strongest among Hispanics, followed by Asians, Africans, and then Caucasians. (That study did not include Native Americans, who have even more IR.)
- In general, as ethnicities get exposed to a Western diet they have a fairly dramatic rise in IR (and probably that’s a better explanation than the “thrifty gene” hypothesis).
Chapter 10 – How Hormones Cause IR
- Too much insulin (from disease, or just from food) makes you insulin resistant.
- Beta cells don’t necessarily die, they just stop working. In many cases, when they get a break on a low carb diet for about eight weeks they may recover. (Cited two studies, one was more successful than the other. I suspect with additional fasting there would be a higher success rate).
- The stress hormones, cortisol and epinephrine, both increase blood glucose and increase insulin resistance (among other effects that prepare you to run away from a predator etc).
- Fatter people have more thyroid hormone, a type of thyroid resistance. It goes down if they lose weight.
- Low thyroid means you’ll have fewer insulin receptors on your fat cells, and vice versa.
- With hypothyroidism, your fat cells won’t take up as much glucose, but insulin will prevent them from burning fat and shrinking.
Chapter 11 – Obesity & IR, Revisited
- Subcutaneous fat vs visceral fat:
- The former is more common in women due to estrogen, latter more common in men.
- Check your waist to hip ratio, less than 0.9 in men and 0.8 in women is a good measurement.
- Fat cell growth:
- Normally fat cells would grow (hypertrophy) to a certain point, and then make more fat cells (hyperplasia).
- Certain medications (TZD), as well as oxidized PUFA’s (and another molecule he mentioned) can prevent proliferation, leading to overgrown fat cells that dump fats and other inflammatory materials back into the bloodstream.
- That’s one reason vegetable oils (by far the most common type in processed foods) can be harmful.
- There’s a formula (insulin x FFA) that reflects the health of your fat cells.
- Ectopic fat:
- Fatty liver from fructose or alcohol, creates insulin resistance in the liver which means the liver breaks down glycogen and keeps pumping glucose into the bloodstream despite hyperglycemia and elevated insulin.
- This results in persistent hyperglycemia, leading to insulin resistance in other body areas.
- The connection between fatty pancreas and insulin resistance is not as clear-cut, but in one study the pancreas fat went away around the same time that insulin sensitivity improved.
- Lipodystrophy is a rare disorder when people can’t make normal fat cells, but they end up with a lot of ectopic fat because the body still needs somewhere to put it.
- Muscles can also become fat or IR.
- (Ceramides are more harmful than triglycerides.)
- Muscles can get IR even before fat does.
Chapter 12 – Inflammation & Oxidative Stress
- Inflammation tends to make IR worse.
- He mentioned various inflammatory conditions including autoimmune, infectious, etc, which are associated with IR.
- Obesity is associated with inflammation, especially visceral fat which tends to hypertrophy and start leaking inflammatory materials.
- Macrophages come and create foam cells which attract more inflammation.
- ROS seem to contribute to IR, or perhaps the other way around, it’s kind of equivocal.
Chapter 13 – Lifestyle Factors
- Air pollution contributes to inflammation, increases risk of IR. This includes PM 2.5 and larger particles.
- First, second, and third hand smoke contribute to IR.
- Nicotine directly stimulates IR in fat, and muscle, and other molecules cause harm as well.
- Things we eat:
- MSG is associated with IR.
- Petrochemicals including BPA are ubiquitous, and contribute to IR.
- Pesticides also correlate strongly.
- Sugar, especially fructose, contributes to IR dramatically.
- Evidence on artificial sweeteners is more sparse, but there’s a very strong correlation with IR and DM2.
- Stevia, erythritol, and monk fruit appear to have less of an effect.
- LPS (from bacteria) is also harmful through immune mediated effects.
- LDL helps convey LPS out of the body, one reason why low LDL can raise the risk of serious infection.
- Low-salt raises risk of IR through elevated aldosterone.
- “Starvation” versus fasting – from his POV, main difference is whether muscle starts decreasing. That mainly happens after you run out of body fat.
- Movement and Sleep:
- Being sedentary even for a short time increases IR. This involves the inflammatory pathway. It’s selective, like when one leg is in a cast. The effect persists for a while even if you exercise again.
- Sleep deprivation also increases IR, and it doesn’t take very much. The effect is larger with light exposure at night.
Part III: The Solution: How can we fight insulin resistance?
Chapter 14 – Get Moving: The Importance of Physical Activity
- The most important thing is to do any exercise (it doesn’t have to be difficult or arduous), but ideally doing at least about 2.5 hours per week.
- It also helps to include some intensity (though reducing intensity for a while makes sense if you’re starting a low carb diet, give your body time to adapt).
- Exercise takes glucose up into muscles independent of insulin, which lowers insulin levels.
- Both aerobic and resistance training are effective, but if you can only do a little bit of exercise, resistance is probably better.
- Keep in mind muscle weighs more than fat, so you won’t be losing as much weight when you do resistance training.
- Cold exposure also improves IR, and activates brown fat. It also increases adiponectin secretion. 64.4 degrees against the skin activates brown fat without making you shiver (at least initially, heh).
Chapter 15 – Eat Smart: The Evidence on the Food We Eat
- Back in the 1950s, a weak correlation between fat and heart disease was “embraced”, later considered to be causation, and turned into dogma, (as documented in “Good Calories Bad Calories” [Gary Taubes] & “The Big Fat Surprise” [Nina Teicholz]).
- Reducing calories temporarily helps lose weight, but weight-loss comes from both fat and lean tissue including muscle.
- Starvation actually induces IR, as seen in patients with anorexia, probably because of stress hormones.
- Overall fiber seems somewhat beneficial, but has limited impact in insulin sensitive people, and it depends on the type of fiber.
- Overall, eating less frequently lowers insulin.
- Some intermittent fasting studies have mixed results. In one study involving 24 hour fasts 1-2x a week several DM2 patients were able to get off insulin quickly.
- With prolonged fasting, hydration and minerals can be important.
- Refeeding syndrome results from a spike in insulin (and movement of certain electrolytes, etc.), so breaking a long fast with processed carbs is a bad idea.
- Circadian rhythm:
- Increased IR in the morning due to cortisol, GH, etc. Therefore, eating starchy foods in the morning is a bad idea.
- Interestingly, fat cells follow an opposite rhythm of being more insulin sensitive in the morning. From that POV, you may store less fat by eating in the evening.
- Studies about people skipping breakfast are kind of equivocal. But he says it would depend on what type of food you’re eating for breakfast. Most people eat a bunch of sugary and starchy food.
- Protein raises insulin, but it depends on your blood glucose levels. In general it raises it about two times fasting level.
- If you’re someone who eats a lot of carbs, protein raises insulin more, because you don’t need it for gluconeogenesis (GNG). However, on low carb insulin doesn’t go up very much in response to protein because insulin would suppress GNG.
- Low-carb (LC)
- LC was the standard of care for diabetes in the 1800’s and early 1900’s.
- Starting around 1950 we shifted away and advised diabetic patients to eat more starches and avoid fat. Since that time, IR has gotten much more common and severe.
- Intuition suggests low-carb is a good option for people with IR.
- He reviews several studies (mainly interventional) on low-carb which support it being an effective intervention for IR or DM2.
- The evidence for LC is so overwhelming that the ADA finally added it as an option.
- Glycemic load vs glycemic index. The former is more important, but often ignored.
- In the A-Z trial, insulin sensitive people could lose weight on a carb rich diet, but IR people did not. They did better on LC.
- Gut bacteria also influences glycemic response to sugary foods.
- People are scared of saturated fat, but if you try to avoid it you tend to replace it with polyunsaturated fat from seed oils.
- Carb restriction has various benefits in the context of IR, including lowering insulin levels, lowering triglycerides, and lowering saturated fat in blood (ironically, eating more saturated fat does this as well).
- Ketones used to be considered metabolic waste, now we understand they’re an important alternative energy and have many signaling properties.
- They increase mitochondria and reduce inflammation.
- They also let energy escape through breath and urine, which is good if you’re trying to burn more calories.
- Ketosis is distinct from ketoacidosis (10-20x ketosis level, and inadequate insulin).
- Ketones also activate brown fat, while insulin inactivates brown fat.
- Several studies including one by Dr David Ludwig have recently shown increased metabolic rate from ketogenic diet. Insulin / carbs actually slow your metabolic rate (this has been known about insulin for many years).
- Other benefits of LC:
- Insulin makes more small dense LDL, and LCHF does the opposite. It also lowers triglycerides and blood pressure. (He cited specific research about each of these and the next several.)
- LCHF also has been shown to improve dementia symptoms, Parkinson’s (limited research), and even migraines (also limited research).
- Low-fat lowers testosterone, LCHF helps restore it.
- A study on PCOS showed dramatic improvements in about eight weeks.
- Possible skin improvements, including acanthosis nigricans, acne, and possibly inflammatory conditions like psoriasis.
- GERD often improves rapidly, multiple studies have shown.
- Lower insulin also slows aging.
- Tons of benefits, but would you rather just take a pill?
Chapter 16 – Conventional Treatments: Drugs & Surgery
- Most people just want something quick and easy, like a pill. Or a “simple” operation. That’s what the medical community mostly leans on.
- Doctors spend a lot more time learning about drugs than learning about lifestyle interventions.
- In the book/PDF he has a list of medications with ratings of how effective he thinks they are.
- Bariatric procedures have side effects, and about 25% of people regain the weight, along with IR and other conditions.
- (Depression or addictive tendencies suggest people are more likely to regain weight.)
- Overall, lifestyle intervention can often completely get rid of the root cause, while these drug and surgical interventions generally do not.
Chapter 17 – The Plan [How to Fix Insulin Resistance]
- Some of the other harmful substances he has mentioned are pretty obvious how to fix. Like quitting smoking.
- Correcting insulin resistance (IR) requires changing food and exercise habits, which is a more dramatic change than just taking a pill.
Measuring / Tracking
- First, check your starting point. Take the IR quiz at the beginning of the book. Get your fasting insulin level checked if you can (via doc, or online lab). Under 6 is good, 8-9 is average but associated with higher DM2 risk.
- Glucose tolerance insulin levels are also useful, as some people have normal fasting but abnormal w/ response to food.
- If your insulin peaks at 30 minutes, that’s good. If it peaks at 60 min, worrisome, 120 indicates definite IR (and much higher risk of DM2).
- Measuring ketones is also useful, if they’re elevated insulin is probably reasonably low, pros and cons of each measuring method.
- DM2 patients can also track daily insulin requirements (which will likely drop within a day if they cut carbs).
- Once you know where you are, you can decide where to go. If your fasting insulin is < 6, you’re probably doing well. If you’re 7-17, you need to make some improvements.
- Resistance training has a bigger bang for your buck with IR, but the most useful exercise is the one you’ll actually do. Consider your limitations and potential excuses.
- Pushing and pulling are a simple but effective combo, even at home. To level up slightly, you could buy some basic weight equipment to use at home.
- Real-life movements are better than isolating your biceps, for example, because they should get stronger in conjunction with your back muscles etc.
- Jerry Teixeira’s YouTube, or Get Strong book are good resources.
- Quantity and duration: Six days a week is ideal, at least two to three hours of total exercise is enough to make a big difference. 20 min minimum and 40 min maximum is his usual approach.
- Intensity is important, but don’t do too much too fast. Let your body adapt.
- If you’re doing aerobic, try interval training. If you’re doing resistance, do sets to failure. This makes aerobic and resistance training more similar to each other.
- Control carbs, prioritize protein, fill with fat, watch the clock.
- “Control carbs”
- depending on your answers to IR survey, rough suggestion: 2+, 5% carbs, 1+, 10% carbs, 0+ 20% carbs (about 50 , 75, or 100 grams of carbs per day. 25% protein for each).
- These numbers aren’t “final”, but a good starting point.
- Try to use lower glycemic load (< 15) when possible, 16-30 is moderate. There’s a list on Harvard’s website.
- “Don’t be so sweet”. Lowering carbs means less sugar, keep an eye on condiments among other things.
- “Be starch smart”. Most packaged foods are a type of card to avoid. The more natural the better.
- “Don’t drink your carbs”. Much bigger insulin response from drinking fruit then eating fruit with the fiber.
- Artificial sweeteners: pros and cons of diff options, some have small insulin responses alone and several increase insulin in combination with carbs. Stevia, erythritol, and Monk fruit appear to be among the better options.
- Fermented foods are often a good option, because the bacteria eat some of the carbs. And because of the probiotic effect.
- Raw sauerkraut, kimchee, authentic sourdough bread, and kefir are good examples. Some things like yogurt usually aren’t really fermented anymore.
- “Prioritize Protein”
- Avoid the temptation to restrict protein, even on a ketogenic diet. 1 – 1.5 g per kg body weight is decent, but you probably need more as you get older.
- Animal products make it easier, but you can still be creative if you’re a vegetarian.
- Getting things that are raised or grown locally is better and more sustainable.
- Avoid monocrops.
- Animals that are free and eating their natural foods are also more ethical and sustainable.
- Don’t be afraid of fatty cuts of meat. Watch out for added sugar in jerky and certain other processed meats.
- “Fill with fat.”
- Saturated is good, from animals, eggs, etc.
- Monounsaturated is good, from olive oil, avocados, macadamia nuts.
- Polyunsaturated can be problematic. In natural sources it’s not a big deal but you get much higher amounts in seed oils, and it’s easily oxidized and more likely to be harmful.
- If you’re heating something, use saturated fat like lard, butter, etc.
- Room temperature dressings could be avocado oil or olive oil.
- Nuts vary in fat content.
- Most of them don’t really matter for IR, a few worth mentioning.
- Magnesium seems to help. Chromium does as well, a study showed significant improvement while supplementing that went away after supplementing.
- Cysteine is a nonessential amino acid that can be made from methionine. In a rodent study it was helpful at preventing IR.
- Calcium doesn’t seem to be beneficial independent of dairy (dairy generally reduces the risk of IR).
- Vitamin D deficiency makes IR worse, so getting enough is important.
- Be careful with meal replacement shakes – they often have a lot of sugar, refined carbs, and/or seed oils. Better options exist but not necessarily at your grocery store.
- Watch the clock:
- It’s good to have periods of time when blood sugar and insulin are low. A simple protocol could be 12 hour TRE daily, 18 hour fasting twice per week, and 24 hours every couple weeks or so.
- He usually skips breakfast, it’s the most convenient to change. If not, eat higher fat / higher protein rather than starchy sugary things with breakfast.
- Practical Advice:
- He provides several meal suggestions for breakfast, lunch, or dinner. The general theme is to reduce carbs, especially refined carbs, and to increase healthy fats as well as protein.
- Even dessert is possible but don’t overdo it, sweeteners like monk fruit, stevia, or erythritol can be okay. There are some bakeries and other companies that make low carb products these days.
- It’s important to take what you’ve learned in this book and translate it into action.
- Make decisions based on data, not dogma.
- Start by changing your breakfast tomorrow (or fasting through it).
- Share what you’ve learned with family and friends, they may benefit from it as well.
- Sometimes friends are not particularly supportive, so be mentally prepared for that.
Why We Get Sick covers a very important topic that most people don’t know much about.
Insulin resistance is the most common chronic disease. So it’s worth learning about.
Understanding insulin resistance will also help you understand how fasting and other lifestyle changes can improve your health.
Dr. Ben Bikman is a prolific researcher and an expert on insulin. In this book, he provides remarkable insights based on a thorough review of the literature.
Unlike a lot of health authors, he’s balanced and nuanced in his explanations, and emphasizes what’s actually been researched.
As he puts it: Let’s rely on data rather than dogma to make decisions about our health.
Hopefully these notes have been helpful to at least one person. 🙂