Walter Kempner is no I don't so he's an interesting fellow kind of a controversial guy from the 1940s and 1950s maybe the 1960s he's a physician who did a bunch of studies with diabetics people that were morbidly obese morbidly obese we're 00:11:59 talking hundreds of pound obesity if your team wants to find like images you can see the study so he has this thing called the rice diet and in the 1950s and 1960s he put people on a very very 00:12:12 high carb very lowfat very low protein diet it was essentially white sugar so sucrose and white rice was the majority of the 00:12:23 diet and they got better they lost I mean some people went from like literally being round to being thin their diabetes got better so he fixed 00:12:36 diabetes with a very high carb very low fat very low protein diet and it was by necessity it was low protein because it was all carbohydrates and the problem is that the human brain doesn't want to do this like so he's controversial because in 00:12:50 order to get his patients to do this he had to like he had to do some crazy things to cajo them and so I'm not condoning his experiments but the science is is interesting and what it says about human physiology to me is is 00:13:03 very compelling that you can give someone a diet of pure white sugar and rice and their diabetes gets better why does their diabetes get better and this is not even short term this is long term 00:13:15 so that in the span of I think it was four to six months he could then liberalize these people's diets and their diabetes did not return so this is really interesting to me and I think it kind of ties into the seed oil 00:13:27 piece and I'm not suggesting that this is a a reasonable therapy for people because what we know about human physiology and the human brain is that if you try to push any of the macros too far our brain really 00:13:39 Rebels humans seem to be able to lose weight by cutting carbohydrates or cutting fat if you cut both of them together you have what's called rabbit starvation and you can lose a lot of weight very quickly but it's very 00:13:52 stressful on the body hormonally if you cut carbohydrates you have a ketogenic diet if you cut fat you have a lowfat diet and if you look at the trials head-to-head of low fat or low carb they both have about the same amount of weight loss so there's some contention 00:14:05 but it doesn't really look like a ketogenic diet is magical for weight loss a like a lowfat diet is magical for weight loss relative to Kido they both work but when you cut both when you cut 00:14:17 the the fat really really low that's interesting to me and this is what happened in the rice diet and they the the fat was so low that these Pro people were probably becoming fatty acid deficient and there's a fatty acid that 00:14:30 you can measure in the human blood it's called me acid Mead and that's an indication of fatty acid deficiency essential quote unquote fatty acid deficiency and so the hypothesis is that one of the reasons this diet might have 00:14:43 worked is because when you restrict fat that much the cell has to turn over those cell membranes in a different way and that probably causes a lot of these polyunsaturated fats that are stuck in the cell membranes to become mobilized 00:14:56 and turn over the human body doesn't make polyunsaturated fats but if you feed someone carbohydrates the human body can make saturated fats and monounsaturated fats but this is essentially an accelerated way to get 00:15:10 rid of what were potentially excess polyunsaturated fatty acids in these people's cell membranes again I don't think this is a good therapy for humans because it's so hard on the brain humans don't want to do this we sort of 00:15:22 gravitate toward like a third fat third carbohydrates and maybe a third protein depending how you're looking at it maybe a little less if you're doing grams or calories but there's some balance of those things that kind of is what our body tends to if you go too low fat your 00:15:35 body will Rebel and you know if you go too low carb your body's like I want some carbohydrates so the indication here is there's something going on in these cell membranes and there's a massive shift that happens in the cell membrane when you get very very low fat 00:15:47 and I think that's having to do with this turnover of these omega-6 fatty acids so there's a couple of ways to do this without going solo fat you can also just get them out of your diet like extremely intentionally and then do more 00:16:00 fats that are saturated in their place and so this is the part where it gets a little bit cumbersome for people to think about but I think that you can get similar results by just having a low linolic acid diet so let's back up for a 00:16:13 moment talk about linolic acid Omega 6 which means that six carbons from the end of the molecule is the first double bond it's an 18 carbon molecule it's polyunsaturated which means it has multiple double bonds and there's a 00:16:28 small amount in ruminant fat so things like cows or goats or bison or lamb sheep deer small amount one to 2% but animals like humans or pigs or 00:16:43 chickens that are monogastric accumulate linolic acid so the more of this fatty acid we eat the more we store we don't have a way to get rid of it like cows do cows can transform it so where do we 00:16:55 find linic acid in the human diet we find it in chicken and pigs that are fed corn and soy so evolutionarily inappropriate diets and you find it in nuts and seeds plant foods and we have a massive 00:17:08 input of this linolic acid into the human diet now because we're feeding our animals corn and soy things that they've never eaten historically and all of our processed food is combined is added with these 00:17:22 seed oils things like corn canola sunflower safflower soybean grape seed these are all seed oils and they contain between 25 and 65% linolic acid so what you have I 00:17:35 think is an evolutionarily inconsistent amount of linolic acid coming into the human diet and just like pigs just like chickens when we eat corn and soy when we eat Foods when we eat seed oils that 00:17:48 have a lot of this linolic acid we store it and I think that over time it accumulates in our cell membranes and in the membranes of our mitochondria these little powerhouses in the cell and causes problems and we can get into how it might cause problems at the cellular 00:18:00 level if you want but that's kind of the the 15,000 foot perspective that we have this this fatty acid that is in our food supply historically but when we are living in a quote naturalistic way in 00:18:13 the forest in the jungle there's really very limited access to foods that are high in this it's very hard to get the amount of seeds that would you would get even in 3 to five tablespoons of seed oils so I've done some content about 00:18:25 this you look at corn oil for instance or rice brand oil is an even better example Chipotle very very popular and I went to Chipotle and I asked what do you cook your food and they said rice brand oil so it's the oil extracted from the 00:18:39 brand of the rice okay they put three to five tablespoons of rice brand oil into a a bowl like a burrito bowl or a burrito with the rice and the beans and the the 00:18:50 meat that are cooking in there to get three to five tablespoons of rice brain oil you'd have to eat something like three to four pounds of rice so something that humans would never ever do right it's the same with 00:19:04 sunflower seeds sunflower seed oil is in almost everything soybean oil is very common corn oil to get 3 to 5 tablespoons of corn oil you have to eat somewhere between 60 and 75 ears of corn 00:19:17 so you can see here that we have now even if we were eating an occasional sunflower seed from a sunflower plant because we're starving as humans historically or we're eating a little bit of rice and getting the oil from the brand or we're EA eating some corn in 00:19:30 Native American population we're never going to get anywhere close to the amount of linolic acid coming into our bodies in 2023 and really this amount has been increasing massively over the last 100 to 110 years

the question is why are the mitochondria not doing their job why is the self not responding to insulin 00:05:34 that's the issue different tissues different reasons but the main one is the liver

insulin takes glucose from the blood and also fats from the blood in the form of triglyceride 00:03:11 and stuffs it in cells for a rainy day

having a high blood glucose is a manifestation of the problem not the problem itself because if you 00:02:34 didn't have the mitochondrial dysfunction you wouldn't have the high blood glucose so the high blood glucose is Downstream of the actual problem 00:02:45 and insulin is a way to shall we say cover up the problem

metabolic syndrome

insulin resistance is actually 00:01:14 Downstream of something even more important that we will talk about called mitochondrial dysfunction

but as the situation continues it may require more and more and more insulin to get the same amount 00:02:40 of glucose into the cells

the vast majority of hypertension high blood pressure the root cause is insulin resistance metabolic disease

many of these patients had high lipids and high blood pressure and they were given beta 00:28:25 blockers and thide diuretics which as you know also have the same consequence as the statins do in in exacerbating insulin resistance

you can take these medications you can expose yourself to the risk of the medications 00:26:57 or or you can change the way you eat you can deal with the true underlying problem insulin resistance

mTOR (mechanistic target of rapamycin) is an important enzyme that regulates things like cell growth, cell survival, protein synthesis, and autophagy. It also promotes the activation of insulin and IGF-1 receptors. This is why the presence of IGF-1 and insulin increases the amount of mTOR. You need to down-regulate mTOR in order to trigger autophagy. As an additional benefit, decreasing mTOR also causes senescent cells to down-regulate the release of inflammatory secretions. This means even if you don’t kill those cells through autophagy, you at least stop them from inflicting damage to the surrounding cells for months afterwards. IGF-1 has a pretty high half life in your body (about 12 hours) so if you want to keep autophagy running at all on a carnivore diet, you’ll also want to practice intermittent fasting.

The nomination has sparked criticism, however, over Mr Azar’s own track record at Eli Lilly, a pharmaceuticals giant that was one of several to repeatedly increased the price of insulin, a life-saving drug used to treat diabetes. 

Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example). This paper reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance.

Objective To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure.Design Randomized trial.Setting Multicenter collaboration at US two sites, August 2014 to May 2017.Participants 164 adults aged 18-65 years with a body mass index of 25 or more.Interventions After 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).Main outcome measures The primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin.Results Total energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval −29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (−6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).Conclusions Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion

Dnmt3a is an epigenetic mediator of adipose insulin resistance

A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake (> 37E%).

Donohue syndrome and Rabson-Mendenhall syndrome usually have homozygous or compound heterozygous mutations in the IR gene, and patients with these diseases have severe insulin resistance together with various symptoms, such as growth retardation, occasional hypoglycemia from infancy, intrauterine growth retardation, and low birth weight [3–6]

Insulin sends a message to our cells that nutrients are available, meaning it’s time to grow and proliferate. When the levels of the hormones drop, it’s a signal to cells that its time to enter a life-extending mode of conservation. Such a system makes evolutionary sense.

The most effective approach has been minimizing fat stores located inside the abdominal cavity (visceral body fat) in addition to minimizing total body fat.[46] Visceral fat, which is more metabolically active than subcutaneous fat, has been found to produce many enzymatic signals, e.g. resistin, which increase insulin resistance and circulating VLDL particle concentrations, thus both increasing LDL particle concentrations and accelerating the development of diabetes mellitus.

Polyunsaturated fats protect against cardiovascular disease by providing more membrane fluidity than monounsaturated fats, but they are more vulnerable to lipid peroxidation (rancidity). The large scale KANWU study found that increasing monounsaturated fat and decreasing saturated fat intake could improve insulin sensitivity, but only when the overall fat intake of the diet was low.[1] However, some monounsaturated fatty acids (in the same way as saturated fats) may promote insulin resistance, whereas polyunsaturated fatty acids may be protective against insulin resistance.[2][3] Studies have shown that substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure. More physical activity was associated with a higher-oleic acid diet than one of a palmitic acid diet. From the study, it is shown that more monounsaturated fats lead to less anger and irritability.[4]