Fat and meat increases insulin resistance. The best paper for this is by Michael Brownlee who won the Banting award in 2004 for the unifying theory of diabetes complications (The Pathobiology of Diabetic Complications: A Unifying Mechanism by Michael Brownlee, Banting Lecture 2004). It's a great paper. I think it's the best paper written on diabetes.

Fat causes insulin resistance. IR for Insulin Resistance which increases insulin levels in the blood trying to compensate for the insulin reistance. The cells are not sensitive to insulin as they normally would be, it still retains its mitogen function, meaning that it induces other cells to divide and replicate. Things that speed up cell division and cell replication are often associated with cancer. Hyperinsulinemia is associated with increased risk of cancer.

Obesity leads to insulin resistance, and our blood sugars start to go up, so our pancreas starts pumping out more insulin to try to force more sugar into our muscles, and eventually the fat spills over into the pancreas as well, killing off the insulin-producing cells, and we’ve got diabetes–in which case we may have to start injecting insulin at high levels to overcome the insulin resistance, and these high insulin levels promote cancer. That’s one of the reasons we think obese women get more breast cancer. It all traces back to fat getting into our muscle cells, causing insulin resistance. Fat from our stomach, or fat going into our stomach.

Diabetes, which can be induced by a high meat diet on a chronic basis, can lead to hyperglycemia. Chronic hyperglycemis is associated with providing more glucose in this context on a continuous basis, is associated with an increased risk of cancer.

A high meat diet is associated with high levels of Insulin Like Growth Factors (ILGF) in the blood. Sometimes you'll see the 1 after ILGF: ILGF-1, which is associated with accelerated cell growth and replication. And is thought to potentially be one of the mechanisms by which a high meat diet increases the risk of cancer. ILGF-1 also decreases the likelihood of a cell going into apoptosis. It's preferable that a cell goes into apoptosis (programmed cell death) than it become cancerous. What I'm talking about here is the metabolic theory of cancer.

There are two main theories of cancer. There is the genetic theory of cancer: vulnerable predispositions exposed to some form of a toxin and thus inducing cancer. Then the second thing is: there are cells simply predisposed to increased risk of cancer by hypoxia and the classic work on that was done by Otto Warburg (see Warburg Hypothesis). He won the Nobel Prize in about 1930 and the gist of it being: a normal cell is part of an organ system: part of the liver, part of the kidney, part of the lung, and it does whatever cells do for that organ. And they work together as a team and their context with the adjacent cells tells them not to divide. These are highly specialized, differentiated cells. The metabolic theory of cancer is that when these cells become hypoxic, for example, they can't get enough oxygen, that drops their ability to produce ATP energy by 18-fold. Sometimes, these cells will de-differentiate and become more primitive and simplistic like a bacteria that's simply out for itself trying to grow and it will no longer pay attention to the cues and signals from the adjacent cells; it will no longer do what it is supposed to do as part of the liver or the lung or the kidney or the pancreas or the bresat or the prostate, and just become cancerous; it grows just for the sake of itself to replicate and it tries to spread and divide (metastasize).

Okay, so things that cause hypoxia are going to increase that risk of a cell becoming cancerous. You know, quite often, a cell that is deprived of oxygen — it just dies. Okay, that's apoptosis when it happens gradually; it's an infarction when it happens suddenly. But these are important concepts. There are lots of things that are associated with increased cancer risk by inducing hypoxia, for example. And then, when it goes into anerobic metabolism, the de-differentiating cancer cell now functioning like an anerobic bacteria, it will extrude lactic acid from its glucose metabolism. They can metabolize 100 times the glucose than the adjacent cells. And by putting lactic acid around in their extracellular matrix, it helps to make its generalized area, making its extracellular mileu more acidic and that favors cancer growth. So things that cause acidosis will have a tendency to increase cancer risk.

The purpose of milk is to help a baby cow grow very quickly. Milk will increase Insulin Like Growth Factor — that's also mitogenic. Insulin Like Growth Factor is like insulin; they are both mitogenic. Mitogenic means: to increase the likelihood of mitosis: cell division.

Meat tends to have higher levels of leucine. Leucine is an amino acid present in higher amounts in meat. Leucine is associated with increased activation of MTOR. MTOR is Mammalian Target of Rapamycin. MTOR is primarily thought of as a nutrient-sensing pathway. It's like a contractor getting ready to build the building. The contractor will not build until he has all the buildng material's equivalent available. Leucine tends to be a rate limiting step. When leucine becomes available, MTOR is more likely to activate a cell to divide. Leucine is also associated with Insulin Like Growth Factor. Leucine is present in higher amounts in general in meat. So that's another reason why meat is associated with increased risk of cancer.

Animal protein and saturated fat are both associated with an increase in LDL cholesterol. Just about everybody knows that studies any nutrition, that saturated fat — the typical meat fat — is associated with an increased risk of blood cholesterol levels. I learnt something interesting from T Colin Campbell. He's the protein expert: the guy who wrote The China Study. That animal protein will also increase LDL cholesterol. And why would it do that? And again, I got this idea from T Colin Campbell and some other reading. It seems that meat induces this hypermetabolic phase towards building stuff. It's sort of a general idea: a loose concept. But it does seems to do that. So that might explain how animal protein would increase LDL cholesterol. If you're going to start cell replication, those replicating cells are going to need cholesterol. They are also going to need some other things; they are going to need some more iron, for example. We'll come to that in just a moment.

By the way, T Colin Campbell is the world expert on protein. He says that milk in paricular is the #1 carcinogen — the most powerful carcinogen in the world.

… as T Colin Campbell — the world protein expert — said that casein and the proteins in milk are the strongest carcinogen in all the world; stronger than everything else that he's aware of that's been tested and he's been studying it for 50 years.

Your red blood cell (in my recent atherosclerosis video (32 mins, 2022), I go into details as to what makes red blood cells more prone to forming atherosclerosis. In the plasma cell membrane on their outer surface. The more higher percentage of saturated fat, the more stiff that membrane. Saturated fats have no double bonds; they tightly inter-digitate. When they tightly inter-digitate, they are more solid. Saturated fat is in general solid at room temperature. Think about it like a pizza. You get a pizza when it's all hot and it's kind-of gooey but you leave it sitting on the counter overnight and it becomes all solid. That's in comparison with MUFAs and PUFAs. MUFAs are monounsaturated fatty acids, especially olive oils, the classic ones as people think of oleic acid. But that's PUFAs - polyunsaturated fats. They have the ability to stay fluid in the refrigerator, for example, more so than other oils. Anyways, saturated fats are solid at room temperature, relatively stiff fats. And when you got a higher percentage of them from a high meat diet, the red blood cells become stiffer. The capillarie are about 5 microns. Red blood cells are about 7 microns. It has to deform to get through that capillary. When the cell membrane is stiff, it's harder for them to get into the capillary, the blood pressure has to go up. When blood pressure goes up, there is more arterial injury at bifurcation sites, and that leads to atherosclerosis (see atherosclerosis video (32 mins, 2022) for a description of carotid artery atherosclerosis). Atheroclerosis narrows down the diameter of the arteries feeding the tissue. When the arteries are narrowed by atherosclerosis, they get less oxygen. When the atherosclerosis becomes severe, that will increase the risk of hypoxia, and potentially increase the risk of cancer.

Meat changes the bacterial flora. There is basically two types of flora. There is plant flora. And that's because plants provide lots of fiber, so they get a different type of flora. Meat and processed food is pretty much the same in terms of the gut flora. There is no fiber in meat and there is typically low fiber in processed food.

So meat changes the gut bacteria. The gut bacteria associated with meat are more likely to not help the colonocytes maintain their tight junctions. So you're more likely to have leaky gut. Leaky gut means increased permeability of the intestinal barrier and that's associated with more systemic inflammation because larger things get through that intestinal lining. It's only a single cell thick!

The intestinal tract is also called the enteric tract. So the lining cells of the intestinal tract are also called enterocytes. Cyte means cells. Colonocytes are the lining cells. Bigger particles of food stuff and bacteria in the food can get into the blood and that incites an inflammatory immune response which causes some systemic inflammation.

Systemic inflammation is thought to be associated with increased risk of atherosclerosis.

You've heard talk about elevated CRPs and that's a whole other subject. But one thing I would tell you: there's a nice book on atherosclerosis by Dr Haverich. He's a cardiac surgeon and he makes the point that in his opinion, he thinks the vasa vasorum — the outer layer of the arteries is the main site where atherosclerosis begins. I actually think he's wrong overall. But he's right in particular. He's right in the sense that I think it does sometimes start there and it does start there in certain vessels. But the reason I'm mentioning all this is: increased systemic inflammation is associated with vasa vasorum — you know, also called tunica adventitia — outer layer atherosclerosis of an artichoke wall.

The problem with getting atherosclerosis in the outer wall not in the center of lumen is that you can then occlude the vas vasorum and infarct the wall of the artery. That can over time have that plaque grow because you'll get neovascularity into the plaque through angiogenesis. Those are fragile vessels. Sometimes they'll hemorrhage and bleed and you get rapid expansion of a plaque which can occlude a vessel and lead to tissue hypoxia.

So this is a mechanism by which inflammation can increase tissue hypoxia .

There's other ways that it could as well through increasing oxidative stress for example. But the point I want to make is meat associated with more inflammation, associated with more atherosclerosis, thus potentially more hypoxia when the atherosclerosis narrowing stenosis becomes severe.

The bacteria in the gut now associated with meat have more of an enzyme called glucuronidase. When your body wants to get rid of estrogen what happens is: the estrogen goes to the liver. The liver conjugates the estrogen with a glucoronic acid; it makes it more soluble in the bottle. Then it's excreted into the bile. The bile goes into your intestinal tract and then you poop it out. That's what normally should happen.

But if you have a bacteria down there, that bacteria from meat it has an enzyme called glucuronidase. It'll deconjugate — take the glucuronic acid off the excreted estrogen and then the estrogen is reabsorbed into the body. So meat eaters will have higher blood levels of estrogen because they can't defecate it out is as effectively.

And by the way, the question arises why do meat-related gut bacteria do all these bad things? And here's the answer:

Because we have been around for who knows how many thousands or millions of years. We've always primarily ate plants! We've got herbivore physiology for intestinal tract and our metabolic system. Because of that over all these years, the plant bacteria have become symbiotic with us. That's an important point. Plant bacteria are symbiotic with humans, meaning that they want to live together with us; they help us out we help them out. Living in our colon is a good apartment for them.

So what that means is the plant bacteria benefit from keeping us alive and healthy whereas the meat-related gut bacteria they could care less if we're alive or not. They haven't been with us long enough to have evolves to be favorable to us. They don't give a rat's tail if we are healthy or not. So that's why they'll often do so many pathogenic things.

We're designed to live with plant-related gut bacteria in our intestinal tract and they do a lot of good things for us. The meat-related gut bacteria are sort of on their own don't really care about us. There's actually a lot of things they do that are harmful to us.

The bacteria and the colon associated with a meat diet include some that will feed on carnitine and they'll convert some of that into something called TMA (trimethylamine). The trimethylamine then goes through the portal vein up to the liver and once they're in the liver they get converted to TMAO (trimethylamine oxide) and that's associated with increased risk of atherosclerosis which can lead to tissue hypoxia, hypoxia then being a risk factor for cancer.

One of the researchers who did this work with Stanley Hazen at the Cleveland Clinic.

The cooking of meat especially when it's cooked at high temperature like grilled meat and like those grill marks have tend to have increased amount of something called heterocyclic amines and those are associated with increased risk of colon cancer. A commonly researched heterocyclic amine is fennel imidazole pyridine.

Meat — red meat by the way — has been declared officially (you know, in sort of like the official circles where it takes forever for anything to happen) a carcinogen.

When you have all the meat fat, you need bile salts to digest fats. So there's more bile salts present in a high fat diet: a high meat diet. And these will accumulate in the colon and they'll get converted from primary bile salts to secondary bile salts and these are carcinogenic: increase the risk of colon cancer.

Meat travels slowly through the intestinal tract. The lack of fiber means: fiber pulls water into the stool and helps speed it along so you poop it out. Meat sits in our colon longer and gets dried out and it tends to putrefy a bit. It's associated with increased risk of colon cancer.

There's another chemical that tends to get made in the colon on a high meat diet called pcaa: polycyclic aromatic hydrocarbons.

You also tend to accumulate N-nitroso compounds in the colon which are associated with increased risk of cancer okay.

Sodium in salt is very often used to flavor meat or to preserve the meat. Sodium is a vasoconstrictor. It inhibits the production of endothelial cell arterial lining cell nitric oxide. This leads to vasoconstriction. Vasoconstriction leads to you'll get hypertension you'll get atherosclerosis. This leads to hypoxia of the tissues. Anything that decreases oxygen supply to the tissues increases the risk of cancer.

Otto Warburg showed that just by decreasing the oxygen supply to cells he could induce them to become cancerous, so hypoxia is bad.

Meat: they're often in association with high sodium but another thing about meat foods: they tend to be low in potassium and magnesium.

Potassium and magnesium which are common in plant foods but low in meat and processed foods are vasodilators they're like the opposite of sodium as as regards to this. And because you lose your vasodilators, your arteries become constricted. So instead of being wide open, they become constricted. Decreases blood supply to the tissues. More hypoxia; increased risk of cancer.

High meat diet is associated with decreased DNA repair system function. And it's another thing I learned from T Colin Campbell (author of The China Study) — he's the number one expert in the world on protein and its relationship to cancer.

Meat is associated with decreased function of the immune system with regard to the NK cells again per T Colin Campbell.

The meat cattle, for example, they're often given estrogen compounds sometimes multiple estrogen compounds to accelerate growth. High estrogen levels in the blood induce a person to gain weight. So they can induce an animal to gain weight. Cattle farms (CAFO) are those cattle operations to rapidly feed them they will give them estrogen to make them grow faster that they then can use them for beef sooner. Concentrated Animal Feeding Operations: CAFO. They will give them estrogens and then that estrogen is still in the animal — some of it, when we eat it and so we eat more estrogens.

Estrogens activate something called the PPARγ switch and that confuses our brain: makes us think that our body's pregnant if you will and it needs to gain weight: to save weight in case the body the baby the future "baby" will need that nutrition.

That's called the PPARγ fat switch and that's also associated with the hypothalamus arcuate nucleus hunger center if you will for gaining weight in the brain.

Meat is high in fat, and it's typically around 40 to 50 percent fat. Even the leanest meats at the leanest you'll get would be about 25 fat. So that's really fat. A typical low-fat vegan diet is 80-10-10; 80% carbohydrate, 10% protein and 10% fat. Just eating a regular piece of meat you're typically eating something that's 40 to 50 fat — that's extraordinarily high and that's why most meat eaters are overweight, especially as they get older.

So obesity is associated with increased estrogen levels. When a person's fat, their fat tissue makes estrogen. Anything estrogen causes cells to proliferate in the breast, in the uterus and in the male prostate. The male prostate is sort of like the male equivalent of the uterus, so it increases cancer.

Higher estrogen levels increase cancer in the breast, the endometrium, of the uterus and in the prostate. Okay, so you don't want that.

In addition to having more obesity besides making more estrogen, you also lower the transport protein in the blood: the steroid hormone binding globulin SHBG and that also increases the activity of the estrogen in the body.

Cows are engineered to be pregnant while they're making their milk. They're making milk while they're pregnant and this means that they have high estrogen levels. A pregnant animal has higher estrogen levels. Remember think about birth control pills. Typical one is EE2 (ethinylestradiol) with vinyl estradiol. So the point of that is the high estrogen's signaling pregnancy so the person doesn't ovulate. And you're now drinking uh a milk a substance with high estrogens. Let's say you're drinking whole milk, for example; associated with increased risk of cancer: breast, endometrium, prostate.

Milk is associated with increased risk of prostate cancer.

We talked about fiber preventing leaky gut and how fiber reduces the risk of colon cancer. And the big thing that the good bacteria do is they produce short chain fatty acids: acetate propionate and butyrate. Butyrate in particular is used for over two thirds of the energy of the colonocytes. When you decrease that amount, the clonocytes don't function as well and they're at increased risk for cancer. That's thought to be another association.

Meat has high heme iron. Heme iron is absorbed in much higher amounts than is plant iron. Eventually it takes decades but a person will tend to develop something I call iron overloads syndrome and they're an increased risk to have high blood levels of ferritin especially if cells die in their liver from fatty liver, for example, or other reasons. And they'll get higher free floating iron in the blood.

Iron is very useful because it has a variable valence and let's say it's most commonly Fe²⁺ and it's often Fe³⁺. It can even be other valences. That's why it's called a transitional metal because it has a variable valence. And in the blood, when it's free in the presence of oxygen, it can start cycling between Fe²⁺ - Fe³⁺ - Fe²⁺ - Fe³⁺ - Fe²⁺ - Fe³⁺. That can lead to the production of free radical oxygens — reactive oxygen species are often abbreviated ROS. There's a great paper on that called iron behaving badly by Douglas Kell, Ph D, from England. It's actually like a genius level paper. So you don't want iron free in your blood.

Iron is something like it's useful where you need it. But if you got it where you don't need it, it can cause all kinds of problems. Start catalyzing the production of free radicals that are like super balls bouncing around breaking things. And they're thought to increase oxidative stress in a significant way and increase the risk of cancer.

Meat having more heme iron and potentially eventually leading to iron overload syndrome. The problem with that too is: iron itself when present in the blood or free in a cell (it's supposed to always be bound to something virtually almost always), it can facilitate the transfer of iron to cancer cells for example.

In order to grow, like I said, it's a good way to think of cancer as like a de-differentiated cell becoming like an anaerobic bacteria. In order to replicate, it needs iron. So normally, the body prevents bacteria from growing and also can help minimize cancer growth by making iron not available free in the blood. But when there's more free iron available that also helps cancer to grow.

Viruses: there's some viruses in meat that's not really proven that I'm aware of and they're thought to potentially increase the risk of cancer. So that's a potential consideration.

That's the old sort of joke you know you're not going to get a direct disease infectious disease as likely from a plant source as you are from (yeah I know sometimes plant can be contaminated with feces etc.), but I'm saying in general an animal can get a disease that you might get as well our metabolism is relatively similar to a lot of mammals it is quite different in comparison relatively speaking with plants.

Constipation again! When a person's constipated chronic constipation (I talked about this in a lecture recently — I think it was the Burkitt lecture and the abdominal pressure syndrome lectures from earlier), you're chronically constipated, you're straining at the stool to defecate and that causes the valsalva maneuver when you tighten your gut to try to push the poop out and that can have your esophagus pop into the chest. This is a very common thing: it's called hiatal hernia.

Once the esophagus is partly in the chest, you get reflux of gastric acid up there and that chronic irritation from the acid into the lower esophagus causes something called Barrett's esophagus which is an inflamed esophagus: the cells start to change — that's called metaplasia and that is at increased risk for cancer formation.

Back in the 1980s, most common cause of esophageal cancer was "smoker drinker cancer". We always called it for squamous cell carcinoma. But nowadays most common form is adenocarcinoma because so many people are fat and constipated from eating a high meat, high oil, junk food diet and they got hiatal hernias, gastroesophageal reflux gerds (GERD).

So that's another way that meat is associated with increased risk of cancer.

The salt that we spoke about earlier being used to preserve and flavor meat is typically sodium chloride. The chloride is a negatively charged ion — an anion. And the body has to balance all its its ions anions and cations — positive and negative ions — because it has to maintain its osmotic equilibrium. If you have too much ions outside of the cells, you know, water from the cell will pass across the plasma membrane and the extracellular matrix in the blood and the cells will become dehydrated and vice versa if there's too much ions inside the cell. So because of that, when one ion goes up, there'll be some compensatory ion that goes down.

When you increase chloride more and more, the body excretes some of its bicarbonate. The bicarbonate is a pH buffer. So if you're losing your ph buffer that will induce a low-grade metabolic acidosis. Acidosis favors cancer growth. So that's another reason to limit your sodium intake. People eating a westernized diet eat far too much sodium. Saltless populations that live out in rural areas that don't add any salt to their food eat about 200 milligrams a day, 200 to 500 the most whereas Westerners are often eating you know 5,000 milligrams a day — way way more salt we're talking more than 10 times more than what we're designed to eat.

Even the low salt diet (some people call 2,000 milligrams a day as a low salt diet) is 10 times more than what an indigenous population will be eating.

Meat has a different amino acid composition. Proteins are basically a bunch of amino acids strung together like a string of beads and meat has a different amino acid composition. It has a lot more methionine and cysteine. These are sulfur-containing amino acids and in their metabolic degradation some sulfuric acid is made. This sulfuric acid induces a low-grade metabolic acidosis. Low-grade metabolic acidosis favors cancer growth.

Methionine is an essential amino acid. Cancer needs methionine to grow okay. Essential means that the body cannot make that amino acid. Methionine is present in higher amounts in meat. Cancer needs that to grow. So the more methionine available, that helps the cancer to be able to grow. And that might be one of the reasons why some people think a low protein diet is beneficial, especially no animal protein.

Again, animal protein is quite different than plant protein because there's more methionine, more cystine and more leucine — those are the three main things that are typically mentioned. Some people also say lysine increases cholesterol levels. So maybe those four amino acids in particular often come up in conversations discussing the differences between meat h protein and animal protein.

Meat increases the risk of inflammatory bowel disease and that's thought to be an autoimmune disease. And inflammatory bowel diseases like ulcerative colitis and Crohn's — these are associated with increased risk of intestinal tract cancer.

Meat having increased choline might be a risk factor for prostate cancer. There's a book called Proteinaholic written by Garth Davis, physician. It's a very good book. He's a bariatric surgeon and he knows a lot and he decided to really try to understand nutrition and i thought he wrote a great book.

Now we're getting into something a little more complicated but we'll just go through fast.

Beef and dairy: they've got increased amount of a sialic acid called Neu5GC. Nue5gc means neuraminic acid and the 5gc is a form that's only present in these animals not normally in humans. But it only differs from you know the human ones like Neu5Ac. It only differs by like a hydrogen group such that the cells of the intestinal tract will actually incorporate this sialic acid into their tissues and other cells but the problem is the immune system recognizes neu5Gc as being different than Neu5Ac. Anad it will thus elicit an immune response and cause systemic inflammation. That systemic inflammation is called xenosialitis from the sialic acid. Sialic acid (i drew a picture of it in my last lecture on atherosclerosis): it's basically very similar. Just think of glucose with a carboxylic acid on it. There's a little more to it than that but that's basically the gist of it.

So anyway, xenosialitis inflammation from eating meat is another reason why meat causes increased systemic inflammation and it'll also increase CRP (C-Reactive Protein) in the blood. That's a little tricky though c-reactive protein. I'll talk about that in atherosclerosis level.

There's some controversy about whether C-Reactive Protein small elevations as detected with high sensitivity CRP tests truly are inflammation. They could also be an indicator released from the muscle a myokine (from the muscle) signal indicating that the muscle is not able to maintain its glycogen stores because of the fat induced rouleaux formation. Okay but that's another topic for another time.

The high protein diets are associated with more of a bacterial infection in the stomach called helicobacter pylori and helicobacter pylori is associated with increased risk of gastric carcinoma. High sodium is also associated with increased risk of gastric carcinoma.

So if you're eating a lot of meat with a lot of salt you're increasing your risk of stomach cancer gastric carcinoma. Same thing, some cancer.

Total meat, red meat, processed meat — they're all associated with increased risk of carcinoma.

Non-organic meat especially is higher in herbicides. Let's say than organic meat or you know grass-fed meat, so to speak, so that's another reason why there's increased risk of cancer.