Metabolic Syndrome

To be completed

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Reminder: Not medical advice, consult doctor before, etc.

What is the general understanding of metabolic syndrome?

Complications for the person, their family, and the public perception

How to think about recovery, management, and responsibility without distributing blame (the emotionally charged aspect of this topic makes it hard to work on recovery without divisiveness). 

Each condition to address:

•  What is it?
• What may cause it and what are the commonalities between sufferers?
  • Endocrine
  • Anatomy/physiology
  • Environmental
  • Evolution/anthropology
  • Fetal development
  • Maternal/paternal health before conception
  • Genetics/epigenetics
  • Immune system
  • Nervous system
  • Psychology
• What are some potential ways of managing symptoms?
  • Breathwork
  • Sleep and Circadian Rhythm
  • Nutrition
  • Trauma recovery
  • Social/Communal integration
  • Exercise
  • Purpose
  • Environment tailored
  • Tools: eustress

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Heart disease and stroke

Cholesterol and Lipid Oxidation

It turns out, half of heart disease patients have normal cholesterol levels yet they have an underlying risk of plaque build-up in the arteries. According to a 2009 study, nearly 75% of hospitalized patients for a heart attack had cholesterol levels that would not put them into the high-risk category.

Cholesterol is an essential molecule needed for healthy cellular functioning. It is also needed in the synthesis of hormones, bile and vitamin D. There are different types of cholesterol with distinct effects:

• Very Low-Density Lipoprotein (VLDL) – VLDL delivers triglycerides and cholesterol throughout the body to be used for energy or for storage.
• Intermediate-Density Lipoprotein (IDL) – IDL helps the transport of cholesterol and fats but its density is between that of LDL and VLDL.
• Low-Density Lipoprotein (LDL) – LDL carries cholesterol through the bloodstream and directs nutrients into the cells.
• High-Density Lipoprotein (HDL) – HDL collects unused cholesterol from the blood and brings it back to the liver for recycling.

It’s not cholesterol itself that’s causing the problems but its oxidation and omega-6 peroxidation that leads to the development of atherosclerosis. Oxidation of LDL cholesterol by free radicals is associated with an increased risk of cardiovascular disease. Oxidized LDL causes direct damage to cells, increasing inflammation and atherosclerosis.

Free radicals and high inflammation damage the endothelium, which the cholesterol then gets stuck to. This leads to the accumulation of plaques and increased risk of heart disease. Additionally, higher VLDL is considered a better predictor of heart disease risk than LDL.

The particle size of lipoproteins also matters. Most of the studies show a positive association between elevated small-dense LDL and cardiovascular disease risk. Small-dense LDL particles can stick into the arterial wall more easily than large particles. They will also stay in the bloodstream for longer, increasing their susceptibility to oxidation. Oxidized linoleic acid located inside LDL particles is one of the primary catalysts for the oxidation of LDL. After linoleic acid becomes oxidized in LDL, that LDL will no longer be recognized by the LDL receptors in the liver but instead it will be recognized by scavenger receptors on macrophages, leading to foam cell formation and atherosclerosis.

Cholesterol bound to saturated fat does not get oxidized that easily because saturated fat is less susceptible to oxidation and is more heat-stable. Saturated fats also decrease the amount of small-dense LDL particles and another type of lipid called lipoprotein(a), both of which are considered better predictors of cardiovascular disease than total cholesterol or LDL alone.

It is true that saturated fat consumption tends to increase cholesterol levels, which is thought to be caused by a reduction in LDL receptor activity in the liver. If there aren’t enough LDL receptors, or they’re dormant, then LDL particles will begin to accumulate in the blood instead of being directed back to the liver. Polyunsaturated fats, on the other hand, increase LDL receptor activity, which lowers the amount of LDL in the blood.

Most of the cholesterol you eat gets esterified and is poorly absorbed. In the short term, cholesterol levels will rise as fats are being distributed around. The body also reduces its own cholesterol synthesis when you consume it from food. Therefore, eating more cholesterol will not raise your cholesterol in the long run. When you look at the mechanism of cholesterol transportation, then higher cholesterol in your blood also means that you’re burning more fat for fuel as well. The body uses very low-density lipoproteins (VLDL) to transport fatty acids, triglycerides, cholesterol, and fat-soluble vitamins around the bloodstream to either burn them off for energy or use in other cellular processes. Once the delivery has occurred, VLDL remodels itself into LDL.

Basically, if you’re using more fat for fuel, then you’ll by mechanism have higher fatty acids in the blood. Cholesterol just happens to be along for the ride.

Intro to lipids & lipoproteins: why there is no ‘bad’ or ‘good’ cholesterol

Here are the current cholesterol ranges in conventional medicine:

• Total Cholesterol – 200 mg/dl (5 mmol/L) or less. However, it’s mostly irrelevant because of not really giving enough detail about HDL and LDL etc.
• Triglycerides – 150 mg/dl (1.7 mmol/L) or less. That’s a good guestimate because you would expect triglycerides to go down when eating fewer carbs and burning more fat for energy.
• HDL Cholesterol – 40 mg/dl (1.0 mmol/L) or more. More HDL tends to be better and if you’re eating a healthy diet, you should see HDL to be actually higher at about 50-60 mg/dl.
• LDL Cholesterol – 100 mg/dl (2.6 mmol/L) or less. However, based on new research on low carb ketogenic diets, the amount of LDL for optimal health can vary greatly between people and is determined by many other things.

If your triglycerides are low and HDL is high, then it means you’re using up those fatty acids. A higher LDL, in that case, isn’t that relevant. Inflammation or C-Reactive Protein (CRP) would then also have to be low.

If your triglycerides are high and you have high CRP, then a higher LDL and total cholesterol aren’t good because you’ll have more inflammation, which will create more scarring of arteries, which then can promote plaque formation.

Some people, around 20%, have a genetic variation that makes them absorb or synthesize so much cholesterol that their diet does influence their blood cholesterol level. Even in these hyper-responders, however, a high cholesterol diet does not generally negatively influence their cholesterol profile.

You can make the argument that high cholesterol leads to atherosclerosis because the plaques are created by cholesterol build-up. However, the root cause of the issue is inflammation and arterial scarring in the first place. If you’d have lower C-reactive protein, then cholesterol would simply be transported around the body by VLDL and if it’s not needed for nutrition, it’d be transited back to the liver by HDL.

The problem with going on a low-fat low-cholesterol diet is that your body would still keep producing its own cholesterol. Arguably you’d be making more of it because of not getting it from food. In fact, a lot of people suffer from low levels of HDL cholesterol, which prevents their body from clearing out cholesterol from the blood. Most Americans don’t have enough HDL to decrease their risk of cardiovascular disease. Crazy enough, low cholesterol levels are actually associated with increased mortality from stroke and heart disease.

Low Carbohydrate ketogenic diets with less than 50 g of carbs a day have been found to be better for long-term cardiovascular risk factor management compared to low-fat diets with less than 30% of calories coming from fat. They can also raise HDL 4x times as much as a low-fat diet. Long-term ketogenic diets reduce body weight, decrease triglycerides, lower LDL and blood glucose, and increase HDL cholesterol without any side-effects.

Here’s how to reduce and prevent the oxidation of lipids:

• Avoid Vegetable Oils and Trans Fats – Canola oil, cottonseed oil, safflower oil, sunflower oil, soybean oil, rapeseed oil and margarine are high in pro-inflammatory omega-6 fatty acids that cause oxidative stress. Because they are PUFAs, they are almost guaranteed to oxidize during manufacturing and after consumption. An exception is olive oil, which is actually a fruit oil, as it reduces low-density lipoprotein uptake by macrophages and decreases the potential of lipid peroxidation. The antioxidants and polyphenols in olive oil protect it from oxidizing during cooking. Unfortunately, most commercial olive oils are either mixed with canola oil or don’t contain the said polyphenols or antioxidants. If you consume olive oil, it should be kept in a cool, dark place and consumed within a few weeks as to avoid spoilage. It should be organic and extra virgin with a manufacture date, expiration date and location where it was made. The greater peppery taste in the back of your throat, the greater likelihood that the olive oil is high in polyphenols and other health promoting properties. You should feel a slight burn in the back of your throat when consuming quality olive oils.
• Vitamin C and E – antioxidants can protect against lipid peroxidation. Vitamin E may reduce deaths from heart attacks by alleviating oxidation of lipids but this should come from food. Supplementing with vitamin C or vitamin E alone can reduce lipid peroxidation to a similar degree but combining them together doesn’t seem to have any additional benefit beyond either vitamin alone.
• Exercise – Intense exercise creates oxidative stress and lipid peroxidation. However, it will result in lower inflammation after recovery. Physical activity is one of the best protective factors to cardiovascular disease thanks to lowering markers of metabolic syndrome, increasing blood flow and improving insulin sensitivity.
• Don’t Over-Cook Food – High-heat cooking, deep-frying, grilling and sauteing promotes oxidation of fats and destroys the antioxidants that would protect against that. Repeatedly heated vegetable oils create lipid peroxidation products. Virtually all cooking oils in restaurants are pro-inflammatory vegetable oils. Even healthy PUFAs, as found in salmon, can promote lipid peroxidation if it’s overheated or fried. That would negate the benefits you get from the omega-3s because they become oxidized. This is why the intake of canned seafood (tuna, sardines, salmon) should be limited, as high heat is used in the canning process, which can oxidize the polyunsaturated fats and cholesterol.
• Excess Iron – Production of reactive oxygen species during iron metabolism causes lipid peroxidation. High iron levels in the body increases the susceptibility to having greater levels of oxidized lipids. Iron overaccumulation promotes oxidative stress and is associated with many diseases like arthritis, cancer, tumors, diabetes, heart failure and liver damage. Too much ferritin also supports lipofuscin formation, which is one of the main age-related pigments that accelerates aging.
• Low copper – Copper deficiency can reduce the function of superoxide dismutase (SOD) increasing oxidative stress and oxidized lipids in the body. Furthermore, copper is needed to strengthen collagen and hence a lack of copper may reduce the health of the arteries and the heart. A lack of copper also reduces the body’s ability to use iron and can lead to anemias commonly thought to be due to iron deficiency.
• Carotenoids from colorful vegetables and pastured animal fat can inhibit lipid peroxidation as well as hemoglobin oxidation. Carrots, turnips, yams and beetroot are great sources for that. Another study found that carotenoids actually increased lipid hydroperoxides in PUFA-enriched membranes. Astaxanthin, however, had the opposite effect and reduced lipid peroxidation. It’s probably due to the oxidation of PUFAs, which astaxanthin can counteract but typical carotenoids can’t. You can get astaxanthin from algae, salmon, and pink/red seafood. Just make sure you’re not overheating it. Eating more saturated fats, as opposed to PUFAs, will also re-compose your cell membranes towards being made of more saturated fats, which are more resistant to oxidative stress. Depending on your past dietary history, it can take several months or years to fully rid yourself of oxidized PUFAs stuck in your cell membranes.
• Spirulina – Spirulina lowers serum malondialdehyde (MDA), which is a marker of lipid peroxidation. This is partly because of the fatty acid profile of algae, as well as its ability to detoxify compounds. Giving oxidized vegetable oil to rats deteriorates their metabolic health, increases oxidative stress and causes liver damage. Spirulina reduces these deleterious effects thanks to its antioxidant properties that inhibit the oxidation of lipids. Taking 2-3 grams of spirulina with meals may lower the oxidation of dietary fats.
• Crushed Garlic – Garlic contains a compound called allicin that gets activated when you crush it. One study found that swallowing whole garlic had no effect on serum lipid levels but crushed garlic reduced cholesterol, triglycerides, blood pressure and MDA. Garlic also has anti-bacterial and anti-fungal properties.
• Turmeric – One of many active compounds in turmeric, curcumin or turmeric itself, can lower lipid peroxidation by enhancing antioxidant enzymes like superoxide dismutase and catalase. This decreases reactive oxygen species and can repair the DNA damage that occurs because of lipid peroxides. Curcumin also chelates iron and thus reduces its potential for oxidation.
• Magnesium – Magnesium deficiency increases the susceptibility of tissues and lipoproteins to oxidation and reduces glutathione levels. Getting enough magnesium is critical for managing overall levels of inflammation and oxidative stress. Because of that, magnesium deficiency is one of the main drivers of cardiovascular disease, because of the increased oxidation of tissues, lipids and chronic systemic inflammation.
• Coffee, Cacao, Olive Oil, Red Wine, Tea, Spices & Avocado – reduce lipid peroxidation in cooked animal foods. Polyphenols in general can lower the oxidation of lipids thanks to their antioxidant content. In adults with type-2 diabetes, pomegranate polyphenols lower lipid peroxidation but not in healthy adults. Consuming either 4 cups of green tea a day or taking a green tea extract supplement for 8 weeks, can significantly reduce body weight, BMI, lipid levels and lipid peroxidation in obese subjects with metabolic syndrome. Both caffeine and coffee melanoidins inhibit lipid peroxidation and reduce the absorption of secondary lipoxidation products.
• Glycine (and potentially glutamine)– Protects against the damage from oxidized seed oils. In alcohol consumption, glycine reduces liver injury and lipid peroxidation. Glycine propionyl-L-carnitine supplementation combined with aerobic exercise lowers lipid peroxidation in subjects with normal lipid levels. Supplemental glycine may be useful for atherosclerosis, heart failure, angiogenesis associated with cancer or retinal disorders and a range of inflammation-driven syndromes, including metabolic syndrome. Glycine alone doesn’t spike insulin or blood sugar. Combining glycine with 25 grams of glucose lowers the blood sugar response by > 50%. Glycine is typically consumed at a dose of 3-5 grams 1-3 times per day.

The most important thing for ensuring good metabolic health and reducing lipid peroxidation is to avoid the consumption of proinflammatory omega-6 fats and vegetable oils. Unfortunately, chronic stress, exposure to environmental pollutants and inflammation in general causes the oxidation of lipids, regardless of what diet you’re on.

Nitric oxide (NO) lowers inflammation and platelet aggregation, which improves the transportation of lipids. Thanks to increased blood flow, it reduces the time all particles stay in the bloodstream, making their oxidation less likely. That is why regular exercise, sauna sessions and eating NO-boosters like beetroot can help with endothelial function.

Instead of using vegetable and seed oils, a much safer alternative is to cook with pastured animal fats like butter, ghee, lard or tallow. They are comprised of mostly saturated fat, which is much more heat-stable and won’t easily become oxidized. Cooking with extra virgin olive oil at moderate and even high temperatures is also fine because the antioxidants and polyphenols protect against lipid peroxidation. However, you would have to know that the olive oil you use actually has those polyphenols because most conventional products don’t.

BEST to WORST COOKING FATS

1. Coconut oil, pastured butter, ghee, lard, tallow and extra virgin olive oil (BEST)
2. Avocado oil
3. Argan oil
4. Macadamia nut/peanut oil (LIMIT)

DO NOT COOK WITH THE BELOW

• Canola
• Rice bran
• Sunflower
• Grapeseed (WORST)

These “heart healthy” vegetable oils (canola, soybean, corn, sunflower, peanut, and safflower) are heated at unnaturally high temperatures, which makes the fats oxidize and go rancid. Oxidized fats accelerate aging, promote inflammation and damage the cells of your body when consumed. In addition to that, before the oils get put onto store shelves, they get processed even more with different acids and solvents to improve the composition of the product. As a bonus, they get deodorized and mixed with chemical colorings to mask the horrible residue of the processing process. If you take it a step further and hydrogenizes the vegetable oil, then it will eventually become more solid and intact.

A Medical Research Council survey showed that men eating butter ran half the risk of developing heart disease as those using margarine. Consumption of trans fats has been linked to obesity, metabolic syndrome, increased oxidative stress, heart disease, cancer, and Alzheimer’s.

It’s not the saturated fat or cholesterol that is driving atherosclerosis but it’s mainly caused by inflammation and sugar that’s making the arteries become inflamed in the first place. Cholesterol is just going there to do its job and tries to heal the injuries but if you keep causing damage to the blood vessels it doesn’t matter how little cholesterol you eat from your diet as your body will still manufacture it from within.

Omega-3 Fatty Acids are an integral part of cell membrane and they regulate many other hormonal processes. They have great anti-inflammatory benefits that protect against heart disease, eczema, arthritis, and cancer. Omega-3s are polyunsaturated fatty acids, which refers to their multiple unsaturated double bonds. Great sources of omega-3s are salmon, grass-fed beef, sardines, krill oil, algae, and some nuts.

There are 3 types of omega-3s:

• EPA (EicosaPentaenoic Acid) and DHA (DocosaHexaenoic Acid) are animal sourced long chain omega-3 fats both essential for the nervous system, brain, and general health. They’re found especially in seafood.
• ALA (Alpha Linolenic Acid) is mostly a plant-based short chain omega-3 fatty acid. Most animals, including humans, can’t directly use ALA so it gets converted into DHA first. Humans can convert only about 8% of ALA into DHA, which is why animal foods like salmon and oysters are much better sources of omega-3s and DHA.

Omega-6 Fatty Acids are also essential polyunsaturated fats. They differ from omega-3s by having 6 carbon atoms at the last double bond instead of 3. Omega-6s are primarily used for energy and they have to be derived from diet. Unfortunately, most people are getting too many omega-6s. The most common omega-6 is linolenic acid (LA). Another omega-6 is conjugated linoleic acid (CLA) with some health benefits. Vegetable oils, processed foods, salad dressings, and some nuts are the highest sources of omega-6 fatty acids.

Omega-9 Fatty acids are monounsaturated fats with a single double bond. These ones aren’t necessarily essential as the body can produce its own. In fact, omega-9s are the most abundant fats in cells. They’ve been found to lower triglycerides and VLDL as well as improve insulin sensitivity. You can get omega-9s from olive oil, and some nuts.

To keep your omega-3 to omega-6 ratios in balance without obsessing over them, eliminate all processed vegetable oils, avoid high-temperature cooking of oils and fats, eat plenty of grass-fed meat, get pastured eggs, mercury-free fish that’s not fed grains and avoid packaged foods. You’d also want to be careful with supplementing fish oil. It’s true that the omega-3s from fish oil supplements can help to lower inflammation but they’re also quite high in polyunsaturated fats and thus easily oxidized. Most of the commercial fish oil supplements out there have been exposed to some heat, sunlight or have simply gone rancid. This actually makes them pro-inflammatory if you take them consistently. Instead, you should focus on eliminating the inflammatory vegetable oils and eat some wild oily fish.

Coconut oil and olive oil that have been used for centuries, however, don’t require nearly as much processing. These fats get extracted by pressing whole olives or dried coconut kernels and then they get bottled. This doesn’t include processing at high heat or exposure to different chemicals. Olive oil and coconut oil are much more vulnerable to temperature and they can go rancid more easily, which illustrates their natural manufacturing ways. Their fatty acid content and ratios are also more favorable for your health.

Saturated Fat

Dr. Weston Price found that saturated fat, such as butter, cream, lard, tallow, bone marrow etc., was a staple in the diets of these very healthy natives. There’s a huge discrepancy with the research done in Western countries where butter is seen so bad that its fat content has to be reduced and swapped out with vegetable oils instead.

Butter actually has many anti-oxidants, such as vitamin A and vitamin E, that protect against the free radical damage that inflames the arteries. It also contains selenium, which is another important anti-oxidant and mineral. The short chain fatty acids of butter, like butyrate, heal the intestinal lining of your gut that prevents inflammation and autoimmune disorders. Medium-chain, as well as short-chain fatty acids, have strong anti-tumor properties.

When Price was doing his research, he described a “vitamin-like activator” that played a central role in the utilization of minerals, vitamins, growth, and protection against heart disease. He called it Activator X, which he found in the butterfat, organs, and fat of animals who consumed green grass, and also in some fish and eggs. Unfortunately, Price died before knowing what this mysterious compound really was. Nowadays we know that Activator X is Vitamin K2, which is a fat-soluble vitamin produced by animal tissues from Vitamin K1.

• Vitamin K1 is mostly found in plant foods and greens. It supports blood clotting and healing.
• Vitamin K2 is divided into many specific forms called menaquinones (MK), ranging from MK-4 and MK-7 etc.
  • MK-4 is found the most in animal foods and it protects tissues against calcium formation and cancer development. It also supports hormones
  • MK-7, MK-8, and MK-9 are mostly found in fermented foods like sauerkraut and miso. They support bone health and hormones much more effectively than K1

K2 is important for mineral absorption and general health. In the context of atherosclerosis, Vitamin K2 also directs calcium into the right place, namely the bones and teeth, instead of keeping it in the bloodstream to cause plaque formation. Vitamin K2 works synergistically with two other fat-soluble activators Vitamin A and D. Vitamin A and D signal the cells to produce certain proteins and vitamin K then activates them. Other minerals such as zinc and magnesium, as well as dietary fat, are needed for the absorption of these fat-soluble vitamins.

Based on current research, you’d want to get at least 100 mcg-s of K2 a day and aim up to 150-200 mcg-s in total. Although humans can convert some K1 into K2, the biggest effect comes from MK-4 utilization, which is most bioavailable in animal foods. Nevertheless, you’d want to be eating foods high in both to cover your basis. Given you don’t need that much K1 from vegetables and K2 is much more difficult to come by, here is a list of foods richest in Vitamin K2, starting with the highest:

• Natto is a Japanese fermented soybean dish with a foul smell. It’s the richest sources of vitamin K2 with a whopping 1103.4 micrograms of Vitamin K2 MK-7 in 100 grams.
• Goose Liver Paste – a pateé type of cream used a lot in French cooking and similar cultures. It’s an easy way of making organ meats more palatable and tastier. MK-4 content 369 mcg/100g.
• Hard Cheeses – cheese should be fermented and unpasteurized for the greatest health benefits. A lot of the vitamins and minerals get lost during processing. MK-7 content 76.3 mcg/100g.
• Soft Cheeses (Brie) – maybe one of the reasons the French didn’t get atherosclerosis had to do with the K2 rich cheeses and pateés that protected them against plaque formation. MK-7 content 56.5 mcg/100g.
• Egg Yolks – specifically the cholesterol-rich egg yolks which where the entire egg gets its nutritional value from. MK-4 content 32 mcg/100g.
• Dark Poultry – meat that’s darker in color such as goose and duck. Much richer in vitamins than white chicken. MK-4 content 31 mcg/100g.
• Butter – MK-4 content 15 mcg/100g.
• Liver and Organ Meats – probably the most nutrient dense foods on the planet are liver, heart, and other organ meats. One of the best sources of dietary vitamin A and D, which are essential for vitamin K utilization. MK-4 content 14 mcg/100g.
• Sauerkraut and Fermented Foods – another form of bioavailable vitamin K1 as well as K2. Paradoxically, the K2 and B vitamin content of fermented foods comes from the live bacteria in them, not the cabbage itself. So, sauerkraut is still actually an animal-based food. MK-7 content 5 mcg/100g.
• Raw Milk and Kefir – more unprocessed food that’s rich in vitamins and some live bacteria. Pasteurized milk just kills all the juice, figuratively speaking. MK-4 content 2 mcg/100g.

Consuming trans fats blocks the actions of Vitamin K2, which would make everything even worse regards to arterial health and inflammation. The reality is that it’s not the butter that’s causing heart problems – it’s the bread that you’re spreading it on. Even worse, if you’re making fried toast with eggs and oil, then you’re literally driving up inflammation through the roof. With a few minor adjustments, such as not using oxidized oils or avoiding the gluten-heavy grains, butter would be one of the healthiest fats in your diet.

Meat Kills?

Eating processed meat such as hot dogs and burgers increases risk of coronary heart disease, stroke, and diabetes. Those meats include many other ingredients such as sugar, chemicals, as well as the gluten-laden wheat bun it’s consumed with. Furthermore, people who eat processed meat tend to follow other poor lifestyle habits, such as not exercising enough, over-eating calories, too much stress, not enough sleep, etc.

Those who eat more red meat also have a tendency to smoke, drink, eat fewer vegetables, and engage in other unhealthy behaviors that increase their risk of cancer.

People who follow a vegan diet already are simply more mindful of their health if they’ve taken the dietary path they’ve chosen. Likewise, a person eating meat and fat can be equally as healthy if they pay attention to these things. Studies that compare vegetarians and omnivores with the general population see both groups living longer than the average person.

Meat is high in protein and eating too much protein is thought to cause kidney disease. Kidneys excrete nitrogen by-products from digesting protein, thus too much protein over-taxes the kidneys. High protein diets may be harmful to those who already have kidney disease but there’s no evidence they damage healthy individuals.

Neither nitrates or nitrites get accumulated in the body. Nitrates from food get converted into nitrites after coming into contact with our saliva. About 25% of the nitrate we eat gets converted into salivary nitrite, 20% gets converted into nitrite, and the rest gets excreted in the urine within 5 hours of ingestion. Studies show no association between nitrites in diet and stomach cancer. What’s more, nitrates may also help boost the immune system and protect against pathogenic bacteria, which is why arugula is a good ingredient to add to your diet.

Combining protein with carbohydrates spikes insulin and makes the entire meal more insulinogenic. Furthermore, you can promote oxidative stress in the body by consuming oxidized fats and cholesterol or if you end up glycating them with glucose.

Any diet you follow, whether that be Paleo, vegan, keto, SAD, or omni-lacto-vege-pescetarian, can be equally as unhealthy and dangerous if you fail to understand the underlying metabolic reactions that occur. What foods you eat, what ingredients you combine them with, when you consume them, how much, at what frequency, your methylation status, and overall biomarkers will determine the final nutritional result. It doesn’t matter what diet you’re on. What matters is how you choose to manipulate nutrient signaling, hormonal profile, and meal timing.

Insulin is the main regulator of energy storage and body weight homeostasis. It promotes weight gain but also makes you become hungrier and more eager to eat. Whenever your glucose drops you want to eat again to prevent hypoglycemia. If a person eats a low-fat high carb diet, then that’s going to end up with another rise in insulin, keeping them in a state of chronically elevated insulin (hyperinsulinemia). High meal frequency is as bad as high carb intake both because of hyperinsulinemia and no opportunity to enter autophagy.

The reason excess cortisol makes you fat has to do with high blood glucose and elevated insulin. If you’re stressed out or have entered the ‘fight or flight mode’, you’re more prone to store fat because of shutting down digestion and raising insulin. The body wants to supply its muscles to run away from danger and fat loss becomes a secondary goal.

Chronic stress promotes chronically high blood sugar and hyperinsulinemia. We also know that insulin resistance walks hand in hand with leptin resistance, that makes the brain desensitized towards satiety signals from food. This is often accompanied by emotional binge-eating, stubborn fat loss plateaus, and less satiety signaling.

Only after the introduction of processed foods from the West do traditional diets become fattening. This you can see happening in China and India who traditionally eat more carbohydrates but now get access to different indulgences and more added sugars.

Avocado a day lowered LDL: https://www.foundmyfitness.com/news/stories/xzcx4l

Early onset atherosclerosis in those with low omega-3 intake: https://www.nature.com/articles/s41430-019-0551-5

Omega-3 cardio protection: https://www.sciencedaily.com/releases/2020/09/200917084102.htm

Vitamin D for blood pressure: https://academic.oup.com/ajcn/article/112/3/527/5857647?login=true

Diabetes

Type-1 diabetes is an autoimmune disorder with a genetic basis wherein the pancreas produces almost no insulin. Without treatment, blood sugar can stay continuously elevated in Type 1 diabetics. Type 2 diabetes is where the body becomes resistant to the effects of insulin. In other words, the body can make insulin, but it doesn’t respond to it as well.

Diabetes increases the risk of cardiovascular disease and stroke by up to 1.8 to 6-fold. Nearly 50% of diabetics die due to cardiovascular disease. Diabetes is also the leading cause of kidney disease and kidney failure.

Diabetic retinopathy can cause blindness and impaired vision, whereas diabetic neuropathy in the limbs can lead to a lack of feeling in the extremities resulting in untreated wounds, which can lead to amputation. Furthermore, diabetes is associated with impaired cognition and neurodegenerative diseases like Alzheimer’s disease.

The first sign of Type 2 diabetes is hyperinsulinemia. However, this can only be picked up by measuring insulin levels after an oral glucose tolerance test, which most doctors do not order. Thus, by the time someone is diagnosed with having impaired glucose tolerance and/or impaired fasting glucose, they have already lost ~ 50% of their beta-cells that are needed to produce insulin. Both Type 1 and Type 2 diabetes are diagnosed as a fasting blood glucose ≥ 7.0 mmol/l (126 mg/dl) or when plasma glucose after a glucose challenge is ≥ 11.1 mmol/l (200 mg/dl) two hours later. Glycated hemoglobin (HbA1c) of ≥ 48 mmol/mol (6.5%) is another diagnosis method. Symptoms of diabetes include dry mouth, increased thirst, fatigue, hair loss, blurred vision, peripheral neuropathy and frequent urination.

Magnesium deficiency has been implicated in pancreatic beta-cell function, reduced DNA repair capacity, insulin resistance, cardiovascular disease, type-2 diabetes, osteoporosis, hyperglycemia and hyperinsulinemia. Copper, zinc, potassium and sodium are also needed for proper glucose metabolism.

Here are the main causes of Type 2 diabetes and/or impaired glucose intolerance:

• Overconsumption of added sugars and sugar-sweetened beverages
• Overconsumption of omega-6 seed oils
• Overconsumption of hydrogenated fats
• Overconsumption of refined carbohydrates
• Physical inactivity
• Obesity and excess body fat
• Visceral fat accumulation
• Low magnesium
• Low chromium
• Smoking and tobacco
• Persistent organic pollutants and plastics
• Lack of sleep and sleep deprivation
• Testosterone deficiency
• Low vitamin D levels

Antioxidant in broccoli for diabetes prevention: https://www.sciencedaily.com/releases/2017/06/170616083130.htm

Older women with type 2 diabetes have a different pattern of brain blood use: https://www.sciencedaily.com/releases/2020/09/200908131132.htm

Patients with type-2 diabetes have been shown to have higher serum and urine copper levels due to molybdenum removing it from tissues and eliminating it through urine. Those with severe nephropathy have a higher urine level of Cu/Mo. Thus, excess molybdenum, when combined with sulfur, may promote the excretion of copper through urine or bile via binding with protein-bound and free copper.

Insulin Resistance

Symptoms of insulin resistance or glucose intolerance include uncontrollable hunger, increased thirst, high blood sugar, high blood pressure, brain fog, lethargy, lightheadedness, easy weight gain around the stomach, stubborn belly fat, elevated triglyceride and cholesterol levels.

You don’t want to ever combine high-carb foods with high amounts of fatty acids because it’ll not only increase insulin much higher but also promotes more inflammation, oxidative stress, and metabolic disorders.

Low carb diets, avoiding processed sugar, and prolonged fasting have been found to be very effective in healing the pancreas and reversing insulin resistance.

• Carbohydrate restriction helps with everything that causes metabolic syndrome, such as high blood sugar, weight gain, elevated insulin, and hypertension.
• Diabetics who ate a normal diet were put on a ketogenic one for 2 weeks and they lowered their triglycerides by 35%, dropped total cholesterol by 10%, ate 30% fewer calories, dropped 4 pounds and improved their insulin sensitivity by 75%.
• Compared to a low carb ketogenic diet, a low-fat diet for four weeks has been seen to raise fasting glucose and insulin.
• Ketogenic diets have been shown to be very effective at losing body fat in dozens of studies.
• Beta-Hydroxybutyrate (BHB) has been found to inhibit histone deacetylases (HDACs) which lowers blood glucose and decreases insulin resistance

However, going very low carb for too long may cause peripheral insulin resistance. If you’re not eating that many carbs, then you don’t need extra insulin either. Decreased insulin signaling itself is still a good thing for increased longevity and the insulin resistance induced by carbohydrate restriction is an adaptive mechanism.

Here are more ways of protecting yourself against insulin resistance:

• Exercise – Working out and physical activity is one of the biggest determining factors to how insulin sensitive you are. The main cause is thought to be muscle contractions causing the glucose receptor GLUT4 to translocate to the membrane. GLUT4 can improve the uptake of glucose through a distinct mechanism that of insulin. This will lower blood glucose and insulin, preventing hyperinsulinemia.
• Get Enough Sleep – Sleep deprivation has been shown to trigger insulin resistance in healthy subjects. Even just a single night of not enough sleep makes you borderline pre-diabetic in the short term. After a bad night’s sleep, your glucose tolerance for the next day is going to be drastically lower.
• Avoid Smoking – Smoking also induces insulin resistance and causes atherosclerosis. It’s causing similar damage to the arteries as does excess glucose in the bloodstream. Eating low carb high fat while still smoking is as bad as eating junk food.
• Lower Your Stress – Chronic stress and cortisol are known to raise blood sugar, blood pressure and insulin, which over the long term will definitely lead to insulin resistance. Cortisol impairs the uptake of glucose by reducing the translocation of glucose transporters such as GLUT4. It also keeps that stubborn visceral fat around your belly. Mindfulness-based stress-reducing activities like meditation and yoga have been shown to improve insulin resistance.
• Get Enough Sunshine – Vitamin D deficiencies are associated with insulin resistance. It’s an essential steroid hormone that influences every cell in your body, including insulin secretion. Vitamin D is also important for protecting against heart disease. The best way to synthesize vitamin D would be to get it straight from the sun but taking a D3 supplement can also be helpful.
• Lower Inflammation – In rats, insulin resistance can be alleviated by fish oil supplementation. This may be partly due to the anti-inflammatory properties of omega-3s that help to fight the inflammation caused by sugar.

Advanced Glycation End-Products (AGEs) are compounds that get formed when sugar molecules react with proteins or fats. AGEs are related to accelerated aging, diabetes, increased inflammation, and mitochondrial dysfunction. AGEs can also interfere with insulin signaling by decreasing insulin secretion, thus promoting insulin resistance.

Inflammation from food and AGE formation creates oxidative stress, which increases gut permeability as well. ‘Leaky Gut,’ allows bacteria, undigested food particles, and unmetabolized toxins to enter the bloodstream and inflame different tissues of the body and lead to obesity.

When it comes to other foods, cooking and processing food in general increases the number of AGEs and other free radicals, such as heterocyclic amines (HAs), and polycyclic aromatic hydrocarbons (PAHs). HAs and PAHs get formed when you cook, grill, fry, or smoke food at high heat. That’s why it’s never a good idea to char your bacon super crisp or let the vegetables turn too crisp – it causes glycation that’s bad for your skin and long-term health.

One study found that omnivores tend to have higher dietary AGE intake than vegetarians, but vegetarians actually end up with higher AGE concentrations in their plasma. The authors figured that this was due to the increased fructose intake of vegetarian diets, which induces oxidative stress to the liver. Leafy vegetables also have a lot of PAHs, comparable to the levels in smoked meat even.

The bottom line is this: keep your insulin and blood sugar low most of the time and stimulate mTOR at times you’d benefit from being more anabolic. Then cycle in between periods of being predominantly ketogenic with occasional refeeds and insulin signaling. That’s how you’ll prevent any dysfunctional insulin resistance or inflammation.

The Case Against Fat

Eating any kind of food, whether that be carbs, protein, or fat, will be significantly more obesogenic with high cortisol. Cortisol will inhibit digestion, release glycogen, raise blood sugar, and spike insulin. That’s why even a “healthy ketogenic low carb high-fat meal” can be damaging to you in the long-term. What’s more, cholesterol and other dietary fats are more prone to become oxidized if you consume them with high cortisol and insulin. Therefore, the underlying issue isn’t as much carbohydrates or fats but more like stress-induced inflammation and hyperinsulinemia.

Daytime favors better glucose tolerance and insulin sensitivity because the body’s metabolic processes are supposed to be more active whereas at nighttime the opposite is true. Blue light exposure from artificial light sources at night is shown to promote insulin resistance, weight gain, and diabetes. The reason has to do with increased cortisol induced by the highly stimulating wavelengths of most blue light sources.

Other factors that determine insulin release include dietary fiber, protein, fermentation, the addition of vinegar, the thermic effect from spices, gut receptors, consistency and satiety signaling.

DON’T COMBINE CARBS WITH FAT! It’s going to result in much higher insulin response and AGE formation than if you were to eat that fat or protein in a low carb meal.

Some people are also less suited to be consuming saturated fat. This is determined by a specific gene called APOE, which has 3 types (APOE2, APOE3, APOE4). The specific APOE gene we have instructs our body on how to make apolipoprotein E, which combines fatty acids to create lipoproteins. Lipoproteins are used to transport triglycerides and cholesterol around the blood. If you have pre-dominantly APOE4 genes, then you’re going to do worse with increased saturated fat and cholesterol intake. Instead, you’d want to be consuming more monounsaturated fats. APOE4 carriers are said to be at a 20% increased risk of Alzheimer’s disease as well. Having APOE2 makes you more suited for a low carb high-fat diet and APOE3 is suitable for both types of diets.

Here are some additional factors to consider that make the case against too much fat:

• Don’t Combine Fats and Carbs – The single most important thing for your nutrition. Both a low carb as well as a high carb diet can be equally good and bad, depending on the situation. You can be healthy and live long on both diets if you keep the macronutrients separate.
• Don’t Be Stressed Out – Cortisol will still make you gain weight and raise insulin. In fact, eating a keto diet with chronic stress can be as detrimental as eating fast food because you’ll oxidize the fats and cholesterol with elevated blood sugar. 
• Avoid Inflammation – Whether that be from processed food, charred meat, oxidized oils, trans fats, or the AGE formation of eating carbs and fats together. 
• Eat Whole Foods – Processed food promotes obesity for a reason – it’s easier to overconsume and it’s less satiating. You may accidentally end up with eating more calories than you need, which is another driver of insulin resistance and fat storage.

The general principles of metabolic autophagy will still apply to any nutrition plan – eat a lot of plants and vegetables for the polyphenols and antioxidants, don’t eat too much meat and protein because of the mTOR stimulation, practice daily fasting with minimal eating frequency, stay low carb most of the time and then cycle with carb refeeds.

Obesity & Metabolic Syndrome

Hyperglycemia and insulin resistance promote oxidative stress and the onset of cytokine storm through HMGB1 and other pro-inflammatory cytokines. Excess glucose decreases the ability of neutrophils to ingest and kill bacteria. Diabetes and hyperglycemia can cause immune system malfunctioning by increasing the levels of dicarbonyls – some of which are by-products of glucose breakdown like methylglyoxal – that interfere with antimicrobial peptides called beta-defensins.

Some microorganisms can become more virulent and replicate faster in high glucose environments because they have access to more energy while simultaneously increasing their glucose uptake and glycolysis. Both low and high glycemic conditions can affect immunity. Malnourishment can suppress immune function and over nourishment leads to immune disorders.

Metabolic Syndrome and Insulin Resistance

Metabolic syndrome is a condition in which at least three or more of the five are present: high blood pressure, central obesity, high fasting triglycerides, high blood sugar and low serum HDL cholesterol. Metabolic syndrome is associated with cardiovascular disease and type 2 diabetes by causing inflammation.

Visceral fat increases the secretion of pro-inflammatory cytokines like TNF, IL-6, CRP, reactive oxygen species, while having less glucose uptake compared to subcutaneous fat, leading to insulin resistance and chronic inflammation. Abdominal visceral fat is strongly correlated with insulin resistance and type 2 diabetes.

Insulin resistance in adipose tissue impairs the oxidation (or burning) of fat and triglyceride storage, causing an increase in circulating free fatty acids (FFAs), triglycerides and LDL cholesterol. Elevated FFAs reduce glucose uptake into muscles by inhibiting protein kinase activation and can lead to liver/muscle insulin resistance, fatty liver disease and pancreatic beta-cell dysfunction. Liver insulin resistance increases gluconeogenesis, or the creation of new glucose, which further contributes to elevated glucose levels and hyperinsulinemia.

Excess calories + physical inactivity -> visceral adiposity leads to…

• Increased leptin, decreased adiponectin
  • Neurohumoral activation
• Increased ROS, TNF, IL-6, CRP
  • Chronic inflammation
• Increased triglycerides, lowered glucose tolerance
  • Insulin resistance

Which results in metabolic syndrome 

Leptin is an adipokine (a messenger that gets released from fat cells) that regulates energy balance, expenditure and immune function like the Th1/Th2 balance. Leptin is a satiety hormone, which is secreted from fat cells when they have enough energy and signals the brain to stop eating. Elevated leptin levels in obesity signals leptin resistance (leptin is elevated because it doesn’t work as well) which is why obese people are constantly hungry.

Adiponectin, however, is an anti-inflammatory adipokine. It is considered a protective factor against developing hypertension, diabetes and myocardial infarction. In obese adults, as body fat increases, adiponectin decreases and leptin rises, which increases risk of cardiovascular disease.

Obesity impairs memory T-cell function and decreases T-cell response to influenza. These changes are not reversed with weight loss, as adaptive immunity has already been altered.

Obesity creates systemic meta-inflammation, characterized by pro-inflammatory cytokines and chemokines.

Obesity and Viral Infections:

1. Obesity = delayed and blunted antiviral responses
2. Obesity = poorer outcomes
3. Obesity = reduced efficacy of antivirals and vaccines
4. Obesity = increased viral shedding, replication and mutation

In addition to elevated proinflammatory cytokines and HMGB1, hyperglycemia also creates hemoglobin glycation damage. This is associated with systemic inflammation, hypercoagulability and lower oxygen saturation among COVID-19 patients. Increased heme breakdown by heme-oxygenase (HO) creates carbon monoxide, which decreases oxygen saturation, increasing deep vein thrombosis, risk of pulmonary emboli and acute coronary syndrome.

The role of hyperinsulinemia in endothelial/vascular inflammation, red blood cell (RBC) and platelet coagulation, sequestration and/or inhibition of vitamin D activation and its downstream consequences:

• Decreased cholesterol sulfate (Ch-S), heparan sulfate proteoglycans (HSPG) and cathelicidin synthesis.
• Carbon dioxide (CO2), carbon monoxide (CO), deep vein thrombosis (DVT), endothelial nitric oxide synthase (eNOS), reduced glutathione (GSH), oxidized glutathione (GSSG), haemoglobin A1c (HbA1c), haem-oxygenase (HO), manganese superoxide dismutase 2 (MnSOD2), nicotinamide adenine dinucleotide (NAD+), plasma membrane (PM), plasminogen activator inhibitor type 1 (PAI-1), pulmonary embolism (PE), reactive oxygen species (ROS), oxygen saturation (SpO2), sirtuin 3 (SIRT3) and type 2 diabetes mellitus (T2DM).

See book for an amazing diagram that demonstrates the effects.

There is quite a lot of evidence to support the personal fat threshold theory:

• Nearly half of Chinese adults (47%) are pre-diabetic. They eat a lot of carbs, but they are not visibly overweight. Asians and Indians seem to have a genetically lower personal fat threshold, which makes them gain more visceral fat and get sick much sooner despite being relatively “thin”.
• Up to 50% of women with polycystic ovary syndrome (PCOS) are not overweight but tend to have a lower PFT.
• Visceral fat accumulation, not total fat mass, is associated with metabolic disorders, diabetes and cardiovascular disease.
• “The principal allostatic load that leads to insulin resistance in the context of obesity is a failure in adipose tissue expansion”. Basically, you develop disease when your body cannot store more subcutaneous fat and starts storing visceral fat.
• People with lipodystrophy have a small limit for storing subcutaneous fat but they are very efficient at storing visceral fat in and around the liver and pancreas. This is exactly what you do not want.

Here are guidelines for measuring your personal fat threshold and metabolic syndrome:

• Fasting Insulin: Normal ranges 3-8 uIU/mL (18–48 pmol/L); moderate insulin resistance 8-12 uIU/mL (48-72 pmol/L); severe insulin resistance higher than 12 uIU/mL.
• Fasting Blood Sugar: Normal ranges less than 100 mg/dl (5.3 mmol/L), prediabetes 100-125 mg/dl (5.6-6.9 mmol/L), diabetes over 126 mg/dl (7 mmol/L).
• Blood pressure over 130/85 mmHg is considered stage 1 hypertension. Stage 2 hypertension is over 140/90 mmHg. Normal blood pressure is below 120/80 mmHg.
• Triglycerides: Normal ranges less than 150 mg/dl (1.7 mmol/L); borderline-high levels 150-200 mg/dl (1.8 to 2.2 mmol/L); high levels 200-500 mg/dl (2.3 to 5.6 mmol); very high levels over 500 mg/dl (5.7 mmol/L or above).
• HDL Cholesterol: Normal fasting HDL is between 40-60 mg/dl. Optimally, it should be between 50-80 mg/dl. HDL below 40 mg/dl can be problematic and a sign of either dyslipidemia or metabolic syndrome.
• Triglyceride to HDL Ratio: Normal ranges 1.0 +/- 0.5; moderate insulin resistance 2-3; severe insulin resistance more than 4.
• HgbA1C: Normal ranges less than 5.6% (<37 mmol/mol); prediabetes 5.7-6.0% (>39 mmol/mol); diabetes higher than 6.4% (>46 mmol/mol).
• HOMA-IR: Normal ranges (0.5-1.5); moderate insulin resistance 1.5-2.5; severe insulin resistance higher than 3.0
• Body Fat Percentage: Normal ranges 5-20% for men and 10-25% women. Anything above 20-25% is an excess amount of fat for men and women, respectively.
• Waist to Hip Ratio: Optimal ratio for women is <0.80 and for men <0.95. Moderate risk for women is 0.81–0.85 and for men 0.96–1.0. High risk for women is >0.86 and for men >1.0. A waist circumference over 40 inches (men) or 35 inches (women) is problematic and promotes metabolic dysfunction.

Metabolic syndrome is diagnosed if you have 3 factors out of the following 5: elevated blood pressure, blood sugar, waist circumference, triglycerides, and low HDL cholesterol.

Causes of Insulin Resistance and Metabolic Syndrome

Elevated levels of free fatty acids and triglycerides in the blood are linked with insulin resistance as well. However, the prolonged elevation of insulin and triglycerides is most commonly caused by the combination of eating refined carbs and fats that increase fat storage and elevate insulin and blood sugar levels.

When you are burning fat, you break down triglycerides into glycerol and three fatty acid chains. However, elevated levels of insulin inhibit the oxidation of adipose tissue fatty acids because insulin suppresses fat oxidation. Since the body is burning carbs, fatty acids remain elevated in the blood for longer, causing dyslipidemia and potential atherosclerotic development. Excess fatty acids will also decrease glucose uptake when eaten together with carbs, keeping the blood sugar elevated for longer.

To prevent this kind of metabolic dysregulation, you should (1) avoid eating refined carbohydrates and (2) eat whole food carbs separately from fat. Calorie restriction, resistance training and intermittent fasting can help mitigate this process to a certain extent but not when you are in an energy surplus.

Humans living in the wild would rarely eat foods high in fats and carbs together. During the summer they would eat more carbs in the form of fruit, vegetables, berries and honey. During the winter, there would be less vegetation and our ancestors relied mostly on animal fats and meat. This is not to say that our ancestors didn’t store plants for winter (i.e., nuts, seeds, berries and other vegetation) but their intake would have gone down. The exception to this pattern is the fall when nuts, acorns and fruit are abundant. All animals will try to deliberately get fat and insulin resistant by eating energy-dense and calorie-rich foods prior to winter.

Physical stress overrides the inhibition of glucose uptake into cells by fatty acids. During physiological stressors, like fasting or exercise, the demand for energy increases but the supply is being depleted. This activates AMPK (AMP-activated protein kinase), which is a fuel sensor that mobilizes the body’s fuel sources and regulates energy homeostasis. AMPK activation causes a metabolic adaptation that protects the heart from a lack of blood flow. With activated AMPK, you can use both glucose and fat for energy production because there’s increased demand for ATP (adenosine triphosphate, which is the energy currency of cells). That’s why exercise and fasting have similar physiological mechanisms in the short-term.

Here are the main contributing factors that cause insulin resistance and metabolic syndrome:

• Excess visceral fat and obesity. Abdominal visceral fat is strongly correlated with insulin resistance and type 2 diabetes. It’s both the cause and effect. A 2015 study from Yale found that the creation of new fat cells was governed by a key nutrient-sensing pathway called phosphoinositide 3-kinase PI3-kinase/AKT-2, which is a part of the mTOR/insulin/IGF-1 pathway. Insulin promotes the storage of nutrients and the growth of new cells through mTOR and AKT-2. It can grow both muscle and fat cells. Visceral fat decreases glucose tolerance and spreads inflammatory cytokines throughout the body.
• High intake of added sugars and refined carbs. Added sugars drive coronary heart disease by inducing insulin resistance and hyperinsulinemia. Sugar, especially fructose, is worse than starch or other whole foods carbohydrate sources. Animal and human studies have shown that replacing starch and glucose with sucrose or fructose, despite isocaloric eating, raises fasting insulin, reduces insulin sensitivity and increases fasting blood sugar. Compared to a diet containing less than 10% of calories from added sugars, a diet that consists of 25% calories or more from added sugars triples the risk of cardiovascular disease mortality. Overconsuming added sugars can also lead to copper deficiency, which further contributes to fatty liver and insulin resistance. The important message is that added fructose, found in things like table sugar and high-fructose corn syrup, are more harmful than starch or glucose when it comes to insulin resistance and impaired glucose tolerance.
• High fructose consumption. The body can store carbs as liver glycogen (about 100-150 grams worth) and exceeding that limit will increase the conversion of glucose and fructose into triglycerides. That disrupts the Randle cycle in a similar way. During a calorie deficit, fructose can also be converted into glucose but some of it will still inevitably become triglycerides. Natural fruit is fine in moderation but it can still promote metabolic syndrome, especially in regards to elevated triglycerides, when consumed in excess. To not cross that threshold, a few servings of low-sugar fruit (i.e., berries) a day is safe. Fructose-sweetened beverages are linked with insulin resistance.
• Sedentary lifestyle. Physical activity is one of the biggest predictors of overall insulin sensitivity and glucose tolerance. It supports glucose uptake by cells and maintains glucose homeostasis in response to carbohydrate meals. Muscle contractions cause the translocation of the glucose receptor GLUT4 to the cell membrane. GLUT4 is able to increase the uptake of glucose through a different mechanism than insulin. So, you can mitigate current insulin resistance or diabetes with exercise-mediated GLUT4 activation. This would help keep blood glucose and insulin lower, preventing hyperinsulinemia.
• Chronic stress and high cortisol are known to raise blood sugar, blood pressure and insulin, which will lead to insulin resistance if chronically elevated. Cortisol inhibits glucose uptake by reducing the translocation of glucose transporters, such as GLUT4. It also directs fat storage more towards visceral adiposity instead of subcutaneous fat. Mindfulness-based stress-lowering activities, like meditation and yoga, have been found to improve symptoms of insulin resistance.
• Sleep deprivation and insomnia have a profound effect on overall insulin sensitivity and glucose homeostasis. Short sleep impairs glucose tolerance, raises blood sugar and cortisol and promotes insulin resistance. Even one single night of partial sleep has been shown to induce the biomarkers of a pre-diabetic in the short term. After poor sleep, your glucose tolerance and uptake for the following day will be severely hampered. That is why you should specifically avoid spiking your blood sugar and insulin with high glycemic foods on days of poor sleep because your ability to metabolize them is impaired.
• Circadian rhythm misalignment increases insulin resistance and decreases pancreatic function. Damaging the master circadian clock in the hypothalamus of rodents makes them insulin resistant in 8 weeks. Shift workers have a higher risk for diabetes, which is due to the reduced glucose tolerance caused by circadian misalignment. Circadian disruption can be caused by travelling across time zones, shift work, irregular sleeping patterns, irregular meal timing and staying up past habitual bedtime. It essentially increases stress and inflammation, making it harder to maintain glucose homeostasis. Studies on time-restricted eating in humans have shown that eating within 8 hours or less shows a higher expression of autophagy genes, sirtuins and better insulin sensitivity compared to eating over the course of 12 hours.
• Blue light exposure at night suppresses the production of melatonin the sleep hormone and can induce insulin resistance. Observational studies have shown a correlation between exposure to light at night with obesity and type-2 diabetes. When food intake and physical activity are controlled, bright ambient light reduces insulin sensitivity in a time-dependent manner in healthy individuals. When optimally aligned with the circadian rhythms, we should be exposed to blue light only during the early parts of the day. In the evening and at night-time, we would primarily see red and amber lights. To protect your circadian rhythms and sleep quality, you want to avoid artificial lights in the evening and consider wearing blue blocking glasses.
• Trans fats and vegetable oils. Things like margarine, corn, soybean, safflower, cottonseed and canola oil promote oxidative stress, inflammation and insulin resistance. They’re highly inflammatory, oxidized and provide zero health benefits. Chronic inflammation also promotes insulin resistance. Giving insulin resistant rats anti-inflammatory omega-3 supplements alleviates their pathology. People who consume high amounts of omega-6 seed oils have a worse lipid profile and markers of insulin resistance.
• Smoking induces insulin resistance and is associated with type-2 diabetes. Both the smoke, and the various carcinogens in cigarettes, contribute to this. In healthy smokers, smoking 24 cigarettes a day can increase 24-hour energy expenditure by about 10% due to activation of the sympathetic nervous system. Smoking also acutely raises lipid mobilization and oxidation of free fatty acids but also very low-density lipoprotein (VLDL), which has a high atherogenic potential. However, smoking cessation is also found to be linked with type-2 diabetes due to weight gain. The greatest risk of developing type-2 diabetes is highest 2 years after smoking cessation. Nicotine and smoking are reported to be appetite suppressing and quitting the habit can mean eating more. To prevent the weight rebound, using nicotine patches or gum can be effective for weaning off cigarettes. Nicotine itself has nootropic effects and regulates AMPK, which is involved with energy balance and fat oxidation.
• Excessive alcohol. Drinking alcohol in moderation is associated with a reduced risk of type-2 diabetes. This appears to be mediated by increased insulin sensitivity, anti-inflammatory pathways and adiponectin. Meta-analyses have found that moderate alcohol consumption may improve insulin sensitivity and decrease fasting insulin in women but not men. However, that would have to apply to alcoholic beverages without added sugars or fructose. What’s more, excessive alcohol and getting intoxicated will cause oxidative stress, which takes away energy from other processes in the body. Alcohol also causes liver damage and promotes the development of fatty liver and visceral fat.
• Magnesium deficiency has been implicated in pancreatic beta-cell function, reduced DNA repair capacity, insulin resistance, cardiovascular disease, type-2 diabetes, osteoporosis, hyperglycemia and hyperinsulinemia.
  • Magnesium supplementation improves fasting blood glucose in people with diabetes and glucose tolerance in those who are at a high risk of diabetes. Supplementing magnesium for 4 months or more significantly improves insulin resistance and fasting glucose in both diabetic and non-diabetic subjects. Magnesium improves insulin resistance in those with low blood levels of magnesium.
  • Hyperglycemia and hyperinsulinemia increase mitochondrial reactive oxygen species (mtROS) production that reduces the antioxidant capacity of glutathione. Magnesium deficiency also reduces glutathione, which is an important antioxidant that helps protect the lungs, especially during viral infections. Insulin resistance and hyperinsulinemia, as found in those who consume high sugar diets, promote renal excretion of magnesium and reduce intracellular magnesium levels.
  • Lower serum magnesium increases thrombotic risk, which makes it important surrounding COVID-19, as COVID-19 increases thrombotic risk. In vivo, magnesium has anti-thrombotic effects and reduces mortality in pulmonary thromboembolism suggesting that magnesium is a natural anticoagulant.
  • Metformin, diuretics, and proton pump inhibitors, which are commonly prescribed to type-2 diabetics, have been shown to cause low magnesium by reducing gastric acidity and magnesium solubility, thus decreasing absorption of magnesium in the gut. Diuretics also increase the elimination of magnesium out the urine.
• Lack of vitamin C may have a contributing role in insulin resistance. Supplemental antioxidants in type-2 diabetes could improve the condition and attenuate diabetic pathogenesis. An imbalance between the declining endogenous antioxidants and increasing production of reactive oxygen species can lead to a state of chronic systemic inflammation that onsets many pathologies. Taking 500 mg of vitamin C twice a day has potential to reduce proinflammatory markers like CRP and IL-6 in obese/diabetic patients. Oral vitamin C increases polymorphonuclear phagocytosis in diabetics and improves glucose tolerance in older subjects with diabetes. A daily dose of 1000 mg of vitamin C (500 mg twice daily) may be beneficial in lowering blood sugar and lipids in type-2 diabetics. Ascorbic acid supplementation improves skeletal muscle insulin sensitivity in type-2 diabetes.
• Lack of chromium can cause poor glucose metabolism and reduced insulin sensitivity. Chromium has been shown to alleviate high glucose and insulin resistance in L6 skeletal muscle by regulating pathways of glucose uptake and insulin sensitivity. Chromium is important for regulating blood sugar. Vanadium deficiency may also be a factor, although more research about the risks vs benefits is needed.
• Insufficient autophagy or cell turnover. Impaired macrophage autophagy causes insulin resistance in obesity because the inflammatory adipocytes produce too many reactive oxygen species, which autophagy would normally clear out. Defective hepatic autophagy in obesity promotes endoplasmic reticulum stress and causes insulin resistance. Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia. Insulin inhibits formation of key autophagy genes. Studies in rodents show that fasting or caloric restriction increases myocardial autophagy in the heart. This helps vital organs survive periods of energy starvation.
• In rats, copper deficiency leads to impaired glucose tolerance. Lower copper intake is associated with increased blood sugar levels in humans as well as rats. Copper deficiency, induced by high fructose intakes, impairs insulin binding and reduces insulin sensitivity. Diabetes can disrupt copper metabolism and copper deficiency can alter glucose metabolism. Accumulation of iron ions in the pancreas, due to copper deficiency and a lack of ferroxidase activity, is thought to cause diabetes.
  • Low copper intake also raises cholesterol and triglycerides and copper supplementation can lower their levels in the blood. In rats, there is an inverse relationship between serum copper and ceruloplasmin and levels of cholesterol and triglycerides. Copper deficiency increases the activity of hydroxymethylglutaryl-coenzyme A reductase (HMGA-CoA reductase), which is the rate-controlling enzyme for cholesterol synthesis, and hence increases cholesterol levels. In rats, a copper deficiency increases hepatic fatty acid biosynthesis two-fold.
  • Copper deficiency also impairs thyroid hormone production. The thyroid is central to regulating metabolic rate and energy balance. There is a positive correlation between serum copper and thyroid hormones in children with congenital hypothyroidism. The ratio of copper and selenium influences thyroid functioning in patients with hypothyroidism. In thyroid disease, the metabolism of zinc, copper, manganese and selenium is abnormal. Low copper status also reduces the conversion of T4 into T3. Serum copper is also regulated by thyroid hormones, which stimulates the synthesis and the export of ceruloplasmin. Less thyroid hormones (hypothyroidism) = decreased ceruloplasmin = copper deficit. In fact, thyroid hormones are known to be needed for kidney sodium reabsorption. Ironically, sodium is needed to bring iodine into the thyroid gland (as well as other tissues such as lactating breast, salivary glands, stomach and intestines) to make thyroid hormones. Indeed, two sodium ions are needed to transport one iodide molecule into these tissues. Thus, thyroid hormone production and sodium status are interdependent on one another.

How to Improve Metabolic Syndrome with Diet

Improving your metabolic health requires improving glucose intolerance, fixing dyslipidemia, losing excess body fat, especially visceral adiposity, overcoming insulin resistance and increasing general fitness.

There is evidence to show that a low carbohydrate ketogenic diet is superior to other dietary strategies for improving lipid profiles in patients with metabolic syndrome that are independent of weight loss. The reason has to do with restricting glucose intake, which lowers basal insulin and blood sugar levels, enabling the body to heal itself.

Ketosis and ketones also provide some unique metabolic effects distinct from glucose metabolism, such as a higher NAD to NADH ratio, SIRT3 activity, inhibition of inflammatory markers like NF-kB, TNF-alpha and COX-2, activation of the Nrf2 antioxidant system and glutathione, suppression of histone deacetylaces (HDACs), which are enzymes that are associated with cancer, aging and oxidative stress and reduced appetite.

• In healthy people, ketones below 7.0 mmol/L have been proven to be safe and even therapeutic. When a low-carb ketogenic diet is implemented, sodium restriction will likely need to be avoided because insufficient sodium induces insulin resistance, creating hyperglycemia.
• Under harsh metabolic conditions, like fasting, carbohydrate restriction or exercise, insulin resistance helps to give the brain glucose that would otherwise be taken up by muscles.
• A period of carbohydrate restriction can be a rapid and effective strategy to fix metabolic syndrome and lower hyperinsulinemia/hyperglycemia. The short-term physiological insulin resistance seen in ketosis is not pathological and not relevant because you are not eating large amounts of carbohydrates. However, for optimal insulin sensitivity and glucose tolerance, it is better to practice cyclical ketosis, so the body doesn’t lose its ability to utilize carbohydrates.

It’s not just about eating less calories than you burn. There are many factors that affect your body’s energy requirements, such as the amount of muscle mass you have, your age, levels of physical activity, sleep, hormones and general metabolic profile. For example, sleep deprivation increases the proportion of energy being obtained from muscle as opposed to body fat. Therefore, calories do matter but you can’t ignore the other dynamic variables that are based on the individual.

Low-carb, ketogenic diets and high-carb, low-fat diets tend to be quite distinct in terms of food selection and macronutrients. Both have been shown to cause similar effects on weight loss and neither genes nor basal insulin are associated with the results. If protein intake and calories are equated, there is no significant difference between these diets. Discrepancies in people’s subjective experience usually come from adherence, sustainability, satiety and the amount of protein consumed.

The thermic effect of protein is 20-35%, carbs 7-10% and fat 2-5%. Individuals who eat a high protein meal end up burning more calories for several hours after eating. The higher thermic effect of protein also contributes to the higher feelings of satiety and fullness.

Here are the benefits of diets with more protein:

• Protein has many vital roles in your body, such as promoting tissue repair, stimulating enzymatic processes and transporting nutrients. It increases metabolic rate, making it easier to lose weight, and supports the functioning of all organs.
• Eating more protein helps with appetite suppression and satiety by increasing the production of certain hormones like peptide YY and GLP-1. It also reduces ghrelin, the hunger hormone for several hours.
• Higher protein intake during dieting promotes weight loss, helps to maintain more muscle and keeps the metabolic rate up. Compared with standard weight loss diets with normal protein and low-fat intake, high protein diets have been found to be more effective.
• Combined with resistance training, higher protein intake increases muscle growth and strength gains. However, more protein will not make you build exponentially more muscle beyond a certain threshold. Current research has seen that limit being around 0.8-1.0 grams of protein per pound of lean body mass.
• Adequate protein intake prevents muscle loss or sarcopenia, frailty and dependence on care taking later in life. It’s observed that muscle atrophy starts to occur even after the third decade of your life, with a 30-50% decrease between the ages of 40-80. Most of the reduction in muscle mass has to do with a lack of resistance training but a slightly higher protein intake can alleviate some these negative consequences.
• Higher animal protein intake promotes bone health and reduces the risk of hip fractures in old people. Falling and breaking bones is one of the biggest concerns related to aging because it predisposes to physical inactivity and further muscle loss, which in turn predisposes to diabetes and other metabolic disorders.
• Higher protein diets can speed up the healing of wounds caused by surgery, injury or bedsores. In this context, intakes above 2.0 g/kg increases the absolute rate of body protein synthesis.

There is no evidence that higher protein consumption is dangerous for kidney function in healthy people. Kidney damage may occur only in people with already existing chronic kidney damage. Excess protein can be converted into glucose through the process of gluconeogenesis. However, this doesn’t appear to cause the same kind of spike in blood sugar as eating sugar or carbs directly because protein-induced gluconeogenesis is regulated based on the body’s energy requirements.

Mediterranean-style diets have protective effects against the development of chronic diseases like metabolic syndrome, hypertension, diabetes and dyslipidemia. They also reduce vascular inflammation, oxidative stress and endothelial dysfunction, which are involved with atherosclerosis.

• When compared to a low-fat diet, a Mediterranean style diet, rich in extra virgin olive oil or nuts, reduces cardiovascular disease risk by 30%. It also lowers proinflammatory biomarkers like CRP and IL-6.
• The Mediterranean diet is composed of a lot of polyphenolic compounds from vegetables, fish, olive oil, nuts, some meat, cheese and a little bit of fruit.

Here are some nutraceuticals and compounds that have been shown to alleviate metabolic syndrome and improve glucose control:

• Curcumin has been shown to reduce NF-kB, which inhibits pro-inflammatory cytokines and TNF-alpha. It also impedes the Wnt/β-catenin pathway, which is linked to obesity. In obese rats, curcumin reduces insulin resistance and leptin resistance within 4 weeks. It also helps to prevent diabetic neuropathy in rats. Supplementing curcumin combined with aerobic exercise improves glycemic control and lipids more than each alone in healthy sedentary overweight women.
• Cinnamon has compounds that improve insulin sensitivity and glycemic control. It has been shown to improve fasting blood sugar, blood pressure and body composition in people with metabolic syndrome. One of the mechanisms appears to be the activation of GLUT4 and expression of insulin-signaling genes.
• Berberine improves insulin sensitivity by suppressing genes of fat storage and regulating adipokines. It has a similar insulin-sensitizing effect to metformin and thiazolidinediones, mediated by AMPK activation in fat cells. In human studies, berberine has been shown to reduce waist circumference, triglycerides and systolic blood pressure.
• Resveratrol activates sirtuins, which have a beneficial effect on glucose metabolism and energy homeostasis. It appears to mimic aspects of calorie restriction through sirtuins, AMPK and NAD+. In patients with nonalcoholic fatty liver disease and insulin resistance, resveratrol improves glucose and lipid status. Patients with metabolic syndrome have better insulin sensitivity, glucose tolerance, and lower body weight from the use of resveratrol. More data is still needed to fully determine the risks vs. benefits of resveratrol.
• Sulforaphane activates the Nrf2 pathway, which has many antioxidant and anti-inflammatory effects on the body. Animal studies have shown sulforaphane to protect against hypertension, dyslipidemia and diabetes thanks to upregulating glutathione via Nrf2. It also lowers cytokine-induced beta-cell damage by suppressing NFkB.
• Quercetin has been shown to lower blood pressure, cholesterol and insulin resistance in rats, ameliorating metabolic syndrome. Higher doses also have anti-inflammatory effects in visceral fat. In humans, quercetin improves waist circumference, postprandial blood sugar and lipids.
• Garlic improves insulin sensitivity and metabolic syndrome in fructose-fed rats. A meta-analysis of 29 studies found that garlic consumption lowers total cholesterol and triglycerides. Using aged garlic for 12 weeks raises adiponectin levels in subjects with metabolic syndrome.
• Omega-3 fatty acids are known to improve dyslipidemia and inflammation in the context of cardiovascular disease. In patients with metabolic syndrome, omega-3 supplementation improves body weight, blood pressure, lipids and inflammatory markers.

In humans, glucose tolerance tends to be higher in the morning versus the evening. Melatonin, a hormone that is produced with darkness, inhibits insulin production by the pancreas. However, your subjective insulin sensitivity depends on your physical activity, muscle mass and general metabolic flexibility.

Strength training increases insulin-mediated glucose uptake, GLUT4 content and insulin signaling in skeletal muscle in patients with type 2 diabetes. GLUT4 is a glucose transporter that allows glucose to enter muscle and fat cells independent of insulin.

The pancreas responds better to glucose in the morning by producing more insulin. Circadian clocks in the pancreas are synchronized to light-dark cycles via signals from the suprachiasmatic nucleus (SCN) located in the hypothalamus, melatonin release, glucocorticoids and body temperature.

• Eating at night may inhibit insulin production because of melatonin binding to insulin receptors and blocking their release, thus keeping your blood sugar elevated for longer.

In conclusion, fixing insulin resistance and metabolic syndrome are one of the easiest and fastest ways to improve your immune system function. It will not only protect you against most other chronic diseases, but it may decrease poor outcomes from viral infections. The best way to do this is to lose weight, especially visceral fat, lower fasting blood sugar and fix insulin resistance. Avoiding calorie-dense processed foods, building muscle, staying physically active, maintaining good circadian rhythm and avoiding inflammatory foods, particularly refined omega-6 seed oils is a great start to fixing insulin resistance.

Energy compensation and adiposity: https://www.sciencedirect.com/science/article/pii/S0960982221011209

Brain damage found in obese teens: https://www.sciencedaily.com/releases/2019/11/191125100405.htm

Obesity + less lean muscle mass lowers cognitive flexibility via the immune system: https://www.sciencedaily.com/releases/2019/12/191217141531.htm

Weight loss with Mediterranean, fasting, and paleo diet: https://www.sciencedaily.com/releases/2020/01/200123170721.htm

Promotes virulence of influenza: https://www.eurekalert.org/news-releases/876833

The effects of obesity mirror the effects of aging: https://www.sciencedaily.com/releases/2020/02/200225122954.htm

Visceral hurts cognition: https://www.eurekalert.org/news-releases/559944 

Reduced brain plasticity: https://www.unisa.edu.au/Media-Centre/Releases/2020/world-first-study-links-obesity-with-reduced-brain-plasticity/