PAUL MASON f | CARBS IN DIET: 100% NON-ESSENTIAL; BRAIN CHOOSES KETONES; LOW CARB EATING WINS

Added: 2026-05-27

[00:00:00]All right. So, good morning. Uh, my name is Dr. Paul Mason. I'm a sports and exercise medicine physician, as most of you, uh, probably know. Today's tutorial, uh, is going to be a little bit different. We're going to base it around 18 multiple choice questions. The question is, which of the following is true of dietary carbohydrate?

[00:00:25]It is an essential fuel to the brain.

[00:00:27]It's essential to replenish muscle glycogen after exercise. It's essential as an energy source for the retina. Or D, dietary carbohydrates are not essential.

[00:00:41]And the correct answer is D.

[00:00:45]As we'll see later, glycogen stores can be maintained on low carb diets. And while glucose is needed for the retina, this can actually be synthesized by the process of gluconneioenesis and dietary carbohydrates are not needed for this.

[00:01:00]So you need to understand that carbohydrates are basically polymers of glucose molecules and after digestion these glucose molecules will find their way into your circulation.

[00:01:14]And this is why dietary carbohydrate is so problematic for diabetes.

[00:01:19]Now the fact that dietary carbohydrate is not essential to fuel the brain uh we need to go back to where that claim was first made and that was first made in this 2002 Institute of Medicine report and that was based on research that showed that the brain on average can metabolize about 100 grams of glucose daily and then they added another 30 gram as a fudge factor. The problem is the ability to use glucose is not the same as the need to use glucose. It's quite possible to fuel the brain on ketones. So this was proven by pioneering metabolic researcher George Cahill. He took three subjects who had been fasted for several weeks, meaning they'd already had low glucose levels, and then he infused them with 20 units of insulin over a 24-hour period. And as you can see, the glucose in their blood absolutely plummeted. It went down to less than 1.5 mill moles a liter. And one subject even went below one.

[00:02:20]And these subjects all remained completely asymptomatic. The neurological function was retained. And the reason is obvious when you look at their ketone levels. The ketone simply replaced glucose as a source of energy.

[00:02:34]There's no obligate need for dietary carbohydrate for the brain. Of course, you obviously need a period of keto adaptation before you go injecting people with insulin and driving their glucose down to the ground. And that period of keto adaptation takes at least 2 weeks and preferably four or more.

[00:02:54]Okay, so question two, which of these diets has the strongest evidence for weight loss with ad libertum intake? So that just means when we're letting people consume as much food as they wish, but food only of a certain type. And I would hope that most of you would realize that the correct answer is B.

[00:03:18]So over the 20-year period between 2003 and 2023, the public health collaboration in the UK identified 71 randomized control trials comparing low carb and low-fat diets in terms of weight loss. And out of those 71 RCTs, 39 found statistically significant results. In other words, the findings were likely not due to random chance.

[00:03:44]And these are the results of the 39 randomized control trials. What you'll note is that in every single one of them, the low carb arm did better in terms of weight loss. Could there be better evidence to demonstrate that low carb diets are superior for weight loss than low-fat diets? And what's perhaps even more surprising is that to many of you this will probably be news. Now you might be interested in reading more about this topic. Uh this is a list of more than a dozen meta analyses on this topic. The the point is the science is comprehensive. The science is in and as doctors we we should be knowing this.

[00:04:29]Which of the following statements is true regarding ketoacidosis and low carb diets? A. Low carb diets directly cause diabetic ketoacidosis in healthy individuals.

[00:04:43]Low carb diet induces keto acidosis by producing excessive insulin in the body.

[00:04:49]C. Nutritional ketosis from low carb diets is the same as diabetic ketoacidosis.

[00:04:55]Ketoacidosis primarily occurs in states of insulin excess or ketoacidosis primarily occurs in states of insulin deficiency. Now the answer is E. And this is why we see ketoacidosis in type 1 diabetics who don't have much insulin.

[00:05:12]The high levels of insulin are protective against ketoacidosis. And you also need to understand there's a distinct difference between ketoacidosis and nutritional ketosis. And the conflation of the two is a reason why many people inappropriately avoid low carbohydrate diets.

[00:05:33]Now keto acidosis has a pH change while nutritional ketosis the pH remains normal. So this is a graph comparing the ketone levels versus pH in diabetic patients. And you can see that beta hydroxybutyrate levels have to pass greater than about 5 mill moles a liter before somebody will enter even a mild acidosis.

[00:06:01]Understand that ketones greater than five even on very strict low carb diets are incredibly rare. So this is a starvation study and it shows that even after 10 straight days of fasting beta hydroxybutyrate levels were below 10.

[00:06:19]Question four, which of the following foods has the highest glycemic index?

[00:06:26]Cornflakes, table sugar, honey, or banana?

[00:06:31]And the answer is a corn flakes. You might be thinking, hang on, that doesn't have as much sugar in it. Cornflakes aren't as sweet as honey or table sugar.

[00:06:40]And the reason is the glycemic index is a measure of how rapidly glucose enters the blood.

[00:06:47]And corn flakes are predominantly as a complex carbohydrate made of glucose.

[00:06:55]Compare this then to other sugars however which contain fructose. So sucrose is a combination of one molecule of glucose, one molecule of fructose.

[00:07:06]Honey has a lot of fructose. Fruit on average is about 50/50 glucose to fructose. You know we know fructose by the other name of fruit sugar. And this fructose is not measured in the glycemic index.

[00:07:22]Now unfortunately fructose is actually proven to be more delotterious to our health than glucose. And this is the big failing of the glycemic index as a measure. you can have fructose rich foods that simply don't get measured in the glycemic index. So you need to understand when we're looking at foods when we're when we're looking at uh you know different sugars and carbohydrates and so on and so forth we need to consider the fructose content.

[00:07:53]Okay, question five. Which of the following is true of keto adapted and this is long-term keto adapted over 9 months endurance athletes? So baseline glycogen stores are deficient. Glycogen stores immediately post exercise are deficient. Glycogen stores 2 hours post exercise are deficient. Or there's no evidence of impaired glycogen storage as assessed by repeat muscle biopsy. You can probably tell this is quite a a leading question and this is actually based on a very very good piece of research uh where they actually did muscle biopsies on athletes who were long-term keto adapted. They compared high carb habitual high carb athletes to habitual low carbohydrate athletes. BL stands for baseline. You can see even assessed by gold standard muscle biopsy. No different in glycogen stores.

[00:08:48]Immediately post exercise again no difference and post exercise 2 hours and this is after the high carb athletes were given a high carbohydrate shake and the highfat athletes were given a high fat shake again there was no impairment of the recovery of glycogen. So we have clear evidence that the that repudiates the belief that glycogen stores need dietary carbohydrate to be maintained.

[00:09:15]That is simply false. And when you understand this, you can begin to understand why this whole myth about uh glycogen being absolutely essential for uh anorobic performance, for power performance, and that being the theoretical basis used to say that power athletes can't get by on low carb diets.

[00:09:35]You can see that that's just a house of card that begins to fall away.

[00:09:40]Now this question was based on some uh very recent research. Uh this was included in the recommended reading uh prior to this tutorial. Um please select the most important mechanism by which carbohydrate ingestion can delay time to exhaustion with endurance exercise.

[00:09:58]Maintenance of glycogen stores. Well, we've perhaps already seen that that's probably not a realistic a probable cause. Reducing oxidative stress associated with fat metabolism. increase ketone body production or reducing exercise to induce hypoglycemia and the correct answer is D. Now this is a very recent paper. One of the authors includes Professor Timothy Nos who obviously knows a thing or two about exercise physiology and it was a blinded crossover randomized control trial. Uh they had 10 male triathletes and they were either on a diet of less than 50 gram of carbs or over 380 gram daily carbs. And what they found that 10 g of carbs per hour in both groups prevented exercise to induce hypoglycemia and increased the time to exhaustion by 22%.

[00:10:50]Now this is quite significant. So it demonstrates the mechanism by which dietary carbohydrates uh can be beneficial and it also speaks to the notion of how much dietary carbohydrate do we actually need.

[00:11:04]There's a lot of uh I guess guidelines indicating we need to have certain amounts of carbohydrate in the glucose and fructose to support our physical performance. Um and I suspect that this relatively new piece of research is going to change that narrative. There was actually two other very important learning points to come out of this paper. So first of all, it took about 4 weeks for the blood glucose levels in the low carbohydrate athletes to stabilize, which is really suggesting that that is a minimum adaptation period. Um, if you're looking at commencing a low carb diet without having it deletteriously impact on your performance. The other interesting thing was that the ketone levels appeared to be unaffected by this lowd dose carbohydrate supplementation indicating that the previous fear that people have had that if you take carbohydrates then you impair um the benefits of following a ketogenic diet that it appears that at least for this dose of carbohydrates that is not the case.

[00:12:06]Okay, question seven. Which of the following statements about lipids is correct? Cholesterol may come in different isomers commonly referred to as good and bad cholesterol.

[00:12:18]LDL is a pathological entity that has no known physiological role in the body.

[00:12:23]Epidemiological research indicates lower serum LDL levels are associated with increased all cause mortality.

[00:12:30]Cholesterol is a type of lipoprotein involved in the transport of triglycerides and eoproteins are enzymes that hydrayze free cholesterol in the circulation.

[00:12:41]Now I guess when I wrote this question I really wrote it uh with a view with a memory that when I was a medical student and a junior doctor I truly didn't understand cholesterol. When I saw cholesterol written on the pathology form and it said cholesterol I assumed that that actually meant cholesterol but it actually doesn't. So when they say cholesterol on the pathology results, it actually means lipoproteins and cholesterol is actually a sterile molecule. It's a molecule that can no more have good and bad forms than water can have good and bad forms. So most of these options here are completely spirious and scientific nonsense um distractors. Um, so when we say it's a pathological lipid that has no known physiological role in the body, well, the body devotes an enormous amount of resources to making something it would be highly unusual if it had no known role. And indeed, it has multiple roles, not least including u as part of the immune response.

[00:13:46]Um, as we'll see that C is actually correct. And this is going to surprise a lot of people because we we call LDL bad cholesterol. you think higher levels must be associated with increased mortality when in actual fact the reverse has been robustly shown to be true as we'll see in a moment um uh point D when I said cholesterol is a type of lipoprotein involved in the transport of triglycerides well no cholesterol is a sterile molecule so and people conflate cholesterol with lipoproteins but they really should not be conflated scientifically that's completely inaccurate and E again was just another complete distractor.

[00:14:25]So, we'll have a look at this British Medical Journal article. It was a systematic review and it looked at money and perspective cohort studies that had over 68,000 participants. And the overwhelming finding was that individuals with the highest LDL levels tended to live longer. That was a finding of 16 of the 19 studies that found that relationship. Basically, the higher your LDL level, the lower your chance of dying. And when we actually have a look at each of the individual studies within there, it doesn't matter how we slice it or dice it. When you can see the cortiles there in the center, comparing the very highest LDL group with the lowest or even just the second lowest, the high LDL levels prove to be superior. And then we have people making arguments about reverse causality that it's you know just when people become very sick that their cholesterol lowers and that's why we see this association.

[00:15:20]This study for example excluded subjects with terminal disease with heart disease with diabetes. They they got rid of those chronic diseases and the results still stayed the same. This study found that there was a 50% reduction in the chance of death in the highest LDL group compared to the lowest. In a nutshell, the findings of this systematic review are robust and it's simply scientifically dishonest or disingenuous to dismiss or ignore it.

[00:15:50]So then still on cholesterol, which of these factors increases the production of low density lipoprotein?

[00:16:00]a high dietary saturated fat intake, low carbohydrate intake, low serum B12, or a low serum vitamin C. So, just pause for a moment and think about what you think to be the correct answer. Traditionally trained doctors would pick A. And you would be surprised to know that there's no proven mechanism by which saturated fat can actually increase LDL. So, this study looked at the impact of three fats. olive oil which contains 19% saturated fat, butter containing 66% saturated fat, and coconut oil which contain 94% saturated fat. And they looked at the impact of those fats on cholesterol levels. Now, the traditional dogma would have you believe that the coconut oil group must have seen significant rises in LDL levels.

[00:16:50]In actual fact, the LDL level in the coconut supplementation group actually fell and it actually reduced by more than the olive oil group. The fact is there's no proven mechanisms by which saturated fat can increase LDL levels.

[00:17:05]It's never been shown and yet somehow this has ended up as an indisputable accepted fact in medicine and it really needs to be overtuned.

[00:17:14]On the other hand, vitamin B12 deficiency has been proven to increase cholesterol synthesis. And not only that, we even understand the underlying molecular mechanisms.

[00:17:30]All right. Now, this is an interesting one. So, this again goes against a longheld dietary wisdom and dietary dogmas. large-scale randomized control trials evaluating the replacement of dietary saturated fat with seed oil derived polyunsaturated fats. That's a mouthful. Basically, they took out saturated fat and they gave people seed oils. They found a increases in all cause mortality, b reductions in all cause mortality, no significant change in all cause mortality, or d these studies have never been performed.

[00:18:04]Now, some of you might pick D, and that's not unreasonable, but that's incorrect. These studies actually have been performed. The unfortunate thing is that many of us doctors have simply not heard about these studies or we haven't looked at the results of these studies. The answer is actually a removing saturated fat from the diet and replacing it with seed oils actually increases all cause mortality. So the first large scale RCT to examine this question was from 1965.

[00:18:36]Heart attack survivors were randomly allocated to receive either a supplement of corn oil or the regular diet. And after 2 years, 48% of those in the corn oil group had had heart attacks compared to only 25% on regular highsaturated fat diets. The next study is much closer to home for us. Sydney diet heart study.

[00:18:57]This was a randomized control trial examining the effects of replacing saturated fat with polyunsaturated fat in men who' had heart attacks. And it found that those Australian males who increased their intake of these seed oil derived fats were 62% more likely to die.

[00:19:16]And finishing in the same year, we've also got the Minnesota Coronary Experiment. This was a double blinded randomized control trial on more than 9,000 men and women. And again, subjects who replace saturated fat with polyunsaturated fats faced an increased risk of death.

[00:19:36]And indeed, this was shown again in the Women's Health Initiative study, now published in 2006. This was a massive study of over 48,000 females, and it had a mean followup of 8.1 years. And not incidentally, it was horribly expensive, costing about $700 million US, which means we don't get a doover. And this modern-day randomized control trial found a 26% increased risk of cardiac complications in those females randomized to a reduced saturated fat diet.

[00:20:09]Now, I wouldn't be surprised if all of this was news to you. Now the reason is that the original investigators weren't completely transparent about these findings. So the Sydney diet heart study for example it was completed in 1973 but the mortality data wasn't published until some 40 years later after the data was actually discovered in a basement.

[00:20:33]The Minnesota Coronary Survey also finished in 1973 and it took 16 years for a redacted version of the findings to be published. And again, it wasn't until 2016 that a more complete version was finally published. Again, after a chance finding of the study data showed up in a basement. And you can't make this up. And as for the Women's Health Initiative study, the only statistically significant finding of a whole study just happened to be left out of the results table and it was never mentioned in any press conference. This vague sentence on page 661 of the publication was the only the single reference to it.

[00:21:12]The finding being that females with a history of heart disease faced a 26% increased chance of complications like heart attacks when they reduced their saturated fat. And follow-up to the Women's Health Initiative study demonstrates that this risk only increased with time. This paper reporting a 61% increased risk of cardiac complications in the reduced saturated fat group.

[00:21:37]Now, nobody really knows why these four randomized control trial studies, the findings haven't been effectively disseminated.

[00:21:45]So, Ivan D. France was a co-principal investigator on the Minnesota Coronary Experiment. And he indicated that may have been due to the difficulty he had in reconciling the study's findings with his belief that saturated fat to be bad.

[00:22:00]So when he was asked directly about the delay in publishing the findings, he stated, "We were just disappointed in the way it came out." So I guess if you take one thing away from this tutorial, please make sure you look at the data yourself that you don't just accept common belief because all too often we find that common belief is incorrect.

[00:22:24]Question 10. Which of the following best describes a primary source of elevated serum palmitic acid levels in the context of metabolic disease? Now what do I mean by this? So palmitic acid or palmitate this is the saturated fat that everybody worries about. We worry about consuming it. And we know from observational data, epidemiological research that people with increased levels of fatic acid in their blood have an increased rates of mortality. They have increased rates of metabolic disease, diabetes, so on and so forth.

[00:23:00]So the question is where does this saturated fat where does this palatic acid come from? So option A it comes from foods like red meat and dairy products which are rich in palmetic acid. Does that make the palmetic acid levels in the blood go up?

[00:23:16]It comes from increased denovo lipogenesis in the liver which turns carbohydrates into palmitic acid or C impaired beta oxidation of palmitic acid in mitochondria or D enhanced absorption of palmitic acid from plant-based oils.

[00:23:33]Now the answer is B.

[00:23:37]The body actually can convert carbohydrate into palmitic acid and this has been proven to be a more significant factor in rising palmitic acid levels than the direct consumption of palmitic acid itself. This is an incredibly important point.

[00:23:56]This study fed subjects on either low carb highfat or sorry low-fat high carb diets or highfat diets. And after 10 days there was a significant increase in palmitate levels in the low fat fed subjects. In effect they found higher levels of this saturated fat in the people who were consuming low levels of that saturated fat. And here's why. Excess dietary carbohydrates can be directly converted into fatty acids via the process called denovo lipogenesis. This graph is from an overfeeding study where subjects consumed carbohydrates in excess of their actual needs.

[00:24:38]So you can see despite consuming excess carbohydrates, the rate of glucose metabolism was relatively constant. And incidentally this busts the myth that you can stimulate your metabolism simply by eating regularly.

[00:24:52]Initially in the first few days a lot of the excess carbohydrates was soaked up in the form of glycogen. It could be actually stored in muscle and a little bit in the liver. But as the glycogen stores became saturated the excess glucose got turned into fat. Denovo lipogenesis literally making fat from sugar. Now you probably know this fat by another name as triglycerides.

[00:25:18]And experimental research shows that feeding carbohydrate increases saturated fats much more than consuming saturated fat itself. Very important point to understand.

[00:25:29]All right, question 11. Which of these plant proteins provides all nine essential amino acids in quantities sufficient to meet human needs? Lentils, wheat, peanuts, and soy.

[00:25:44]The answer is soy. This is one of the few plant proteins that provides all of the essential amino acids in near adequate amounts. Lentils are low in methane. Wheat is low in lysine and peanuts are deficient in both. So soy protein is widely considered to be the most complete source of plant-based protein. Although methionine is still a limiting amino acid, this study for example found that skim milk resulted in a 43% higher muscle protein synthesis rate than soy milk.

[00:26:18]So the fact is most plant proteins are incomplete and you also need to be familiar with something called protein complementation which is if you have vegan or vegetarian patients uh they need to combine plant proteins from different sources to achieve a more complete amino acid profile.

[00:26:40]Question 12. Which of these cannot be found in red meat?

[00:26:45]torine, genine, creatine, and vitamin C.

[00:26:49]And the answer is B, and genine. This is an isoflavone that is found in soy protein. And it actually binds to estrogen receptors and therefore it's got estrogenic activity, especially in states of low background estrogen, such as in a male or in a menopausal state.

[00:27:07]Now, this question, I really wrote this to make the point that red meat is nutritionally dense. There's a list of about a dozen nutrients that are either absent or deficient in plant foods which are contained in red meat. So please don't just consider red meat to be a protein which we often consider it.

[00:27:29]Please do consider it as a source of micronutrients as well.

[00:27:34]Now you might be pondering the vitamin C option uh because everybody knows that red meat is deficient in vitamin C. And if you're looking at the USDA nutrient data for beef, you would see that indeed meat doesn't have any vitamin C. The thing is this data was formulated without actually measuring vitamin C levels. They assumed it was zero and simply accepted it and repeated it without question. When it's actually tested though, we find that red meat does contain vitamin C, which is no doubt what we would have predicted if we were students of history. So, Arctic explorers for a long time have used fresh meat to treat scurvy, as did Napoleon's army during the 1801 siege of Alexandria, where they consumed horses who had perished in battle. Okay, question 13.

[00:28:31]Which of the below statements concerning anti-nutrients is incorrect? Now, many of you probably have never even heard of the term anti-nutrient. It sounds pseudoscientific, but it is absolutely an accepted concept. A anti-nutrients contained within corn have been shown to completely inhibit absorption of zinc.

[00:28:53]Concurrent consumption of vitamin C can eliminate the impact of anti-nutrients.

[00:28:59]C. Anti-nutrients such as phitates, tannins, and oxalates can reduce the bioavailability of minerals like iron, zinc, and calcium by binding to them in the gut. The low absorption of iron from legumes, approximately 1 to 2%, is primarily due to anti-nutrients.

[00:29:17]Anti-nutrients may impact the absorption of protein by forming insoluble complexes and inhibiting proteolytic enzymes.

[00:29:25]The correct answer I think I may have uh miswritten this question.

[00:29:32]So anti-nutrients within corn completely inhibit absorption of zinc. That is absolutely correct. Concurrent consumption of vitamin C can eliminate the impact of anti-nutrients. Well, no.

[00:29:44]So the correct answer here or the incorrect answer is actually B. So talking about why um let's have a look.

[00:29:54]This study fed subjects oysters and measured their zinc absorption.

[00:29:59]And you can see they managed to absorb a good amount of zinc as you can see by the area under the curve.

[00:30:07]But when we fed them the same meal of oysters with black beans, we significantly attenuated the absorption of zinc. You can see it's probably down by 2/3.

[00:30:18]But look what happened when they were given corn.

[00:30:21]The absorption of zinc reduced to all but zero.

[00:30:26]This is the effect of anti-nutrients.

[00:30:28]These are compounds within typically in plant foods that bind nutrients and prevent their bio or limit their bioavailability for human digestion.

[00:30:38]As for iron, in the question we referred to iron having a bioavailability of 1 to 2%. This paper found that iron in five commonly consumed legumes which it must be said are commonly recommended as a source of iron for vegetarians was only 1 to 2%. So please have some awareness of these compounds within plant-based foods phitates and tannins and oxalates and so on and so forth. These change the amount of nutrients that we can actually digest and absorb from food. So, just because it says X mg of iron on the label doesn't mean that you're getting X millig of iron.

[00:31:20]Question 14. Which of the following is incorrect?

[00:31:24]Dehydration up to 3 to 4% in well-trained cyclists does not impair physical performance? Observational field data have reported dehydration levels of 6.6 6 to 11.7% body mass in male marathon winners. Observational research identifies most successful marathon runners drink fluids to first.

[00:31:48]Maintaining body weight is an effective means of avoiding dehydration and improving exercise performance. Muscle glycogen depletion results in the release of found water. A 3:1 ratio.

[00:32:02]Uh that ratio that is listed there is incorrect actually. That's meant to be uh uh one to three. The electrolytes contained in sports medicine drinks are generally considered sufficient to prevent exercised associated hyponetreia. And the correct answer here that I was actually looking for was D.

[00:32:22]Let's have a look at some really interesting studies on this. And the reason I've done this, I've I've been in many club rooms, elite level sports, where I've seen dieticians come up and put players on scales to make sure they haven't lost any body weight over the course of the game, otherwise they're dehydrated, and that's considered problematic and you know, going to affect their performance. And they're told to strictly hydrate. And we we tell athletes to hydrate so their urine remains a light straw color because anything that's uh approaching yellow is a proof of dehydration and these are simply incorrect and bad practices.

[00:33:03]So first of all this meta analysis concluded that up to 4% body weight dehydration didn't alter cycling performance and this study was quite interesting. So they looked at 13 international marathons and they looked at the weight loss in the winners and the minimum body weight that they actually lost was 6.6%.

[00:33:24]Which tends to suggest if you're not losing at least 5% of your body weight you're probably not going to win a marathon which is quite interesting. Now understand that glycogen in the muscles you are going to have some glycogen depletion but as you deplete that glycogen you're also going to lose some water. You're going to release water. So that is going to be a an insensible loss that you can't control, but it's not the same as dehydration. So you're going to have a degree of body weight loss through that as well. And so essentially if uh it's been shown that if you're not losing weight, you are at risk of exercise to associated hyponetriia as well. So there are consequences to doing this. Also uh one of the points is that uh the job of the kidneys is to concentrate the urine. So we know that one of the first signs of kidney failure is loss of concentrating capacity. The kidneys want to concentrate. They want to give you yellow urine. They want to give you a highly osmolar urine. So we should let the kidneys just do their job um and not try and interfere. If you're you've got healthy kidneys and you're drinking enough that your urine is light straw colored as is often recommended or encouraged, you're basically overcoming your your natural kidney function. So, uh just be mindful that overhydration probably causes more problems or can cause significant problems and drinking to thirst is a very good notion. uh during athletic events you reduce the risk of exercise associated hyponetriia and it also appears to be very consistent with um good sporting performance. What is the approximate mean peak fat oxidation rate of high carbohydrate endurance athletes? So these are athletes on a traditional diet that we traditionally recommend lots of sports gels, lots of Gatorade, lots of pasta, carb loading, so on and so forth.

[00:35:20]Now the answer is B. It's usually considered to be about.5 maybe 6.7 g of fat per minute. So if we have a look at this study here um this was the study we saw earlier um with the glycogen biopsies and the high carb athletes in this study they were shown to have a mean peak oxidation of 67 g per minute. Um but when we compare it to the low carb athletes, you know, they had a mean peak fat oxidation of over 1.4 gram a minute. So a significant difference in their ability to use fat as an energy substrate.

[00:36:02]Now if we actually graph this against V2 max here you can see so elite marathoners they'll race at about 80% V2 max and you can see at about 82% V2 max the low carb athletes are still burning a lot of their energy from fat. And it's constantly being said oh you can't do any kind of exercise with any kind of you know once you get up in the V2 max you just can't burn fat. Well, this is simply being shown to be false. You actually can at a fairly significant rate. And if we actually, you know, consider how this affects your glycogen stores, we can see that you'll actually um, you know, preserve a lot of your muscle glycogen stores simply because you're burning more fat. And there's other benefits to burning fat as well. Uh, question 16, which of the following is true? weight change is independent of the macronutrient source of energy. So, but that means, you know, it it doesn't really matter if you're having, you know, fat or carbs or protein. You know, it's the the calories, the total number of calories that will affect your weight loss. Uh B, deferring hormonal responses to macronutrients influence weight change.

[00:37:17]C processing of food to alter solubility does not influence weight gain. and D, insulin increases energy availability.

[00:37:27]And the answer is B. And it it's to do with insulin. D was actually a distractor. Insulin actually reduces energy availability. And this is going to be a very important concept later when we go through the case-based discussions. Um, and the reason that insulin, it's important to understand insulin can impact energy availability is because carbohydrates stimulate the release of insulin. So, first of all, let's have a look at the evidence that insulin may actually contribute to weight gain.

[00:38:00]This 2007 cohort study followed youth for eight years and they stratified them by the insulin level and only 2% of those with the lowest levels of insulin in the bottom 25% became obese over the 8-year period.

[00:38:18]Now those with the highest levels of insulin they had 36 times greater risk of developing obesity. they had a 72% risk of becoming obese. So, we've got good evidence that insulin is actually fattening. And we also know that when you consume an isocchloric amount of carbohydrates, it leads to a much more a significant increased rate of insulin release compared to fat.

[00:38:48]And it's this carbohydrate induced insulin release that can is a major factor for weight loss. As we showed you earlier with all the randomized control trials comparing low-fat diets to low carbohydrate diets, this is why low carbohydrate diets are so superior in terms of weight loss.

[00:39:07]Now, Professor Cara Ebling and Dr. David Lewick, they were principal investigators on this study and it compared lowfat and low carb diets and it looked at something called energy expenditure. So after losing weight on an energy restricted diet uh the subjects were randomly allocated to diets either low carb or low fat and the protein was held constant. Now there was an interesting wrinkle in this research.

[00:39:32]So the researchers wanted to keep the weights of the subjects stable but the problem was the low carb diet group kept on losing weight and the researchers actually had trouble maintaining the weight on the low carb diet. So they actually had to significantly increase the caloric intake in the low carb group to prevent weight loss. They didn't have that problem in the high carb group.

[00:39:56]Now at the end of the day, this was a five month rigorously controlled randomized control trial. And it found that the total energy expenditure of subjects on a low carb diet was 300 kilo calories a day greater than those on the high carb, low-fat diet. They essentially got a free lunch equivalent to an hour's bike riding every day and they were calorically controlled. The only difference was the change in macronutrient composition on the diet.

[00:40:26]Okay. Which of the following is incorrect? Inadequate phosphate impairs ability to form bone or muscle. Sodium depletion adversely impacts bone health.

[00:40:38]Inadequate nitrogen, phosphate and potassium can impair muscle synthesis.

[00:40:42]Enlargement of fat stores requires both glucose and protein. And the incorrect option is D. Fat store does not require protein. It only requires glucose.

[00:40:54]So body tissues are made up of specific nutrients. And each of these nutrients must be present in the correct proportion for proper tissue formation.

[00:41:03]If any nutrient is deficient or imbalanced, the development of that tissue will be impaired. And not only can this hinder healing, but surplus nutrients not used for tissue repair can be converted into energy and stored as fat. And that's why ensuring complete nutrition is important. And this was shown elegantly in this 1975 study. So 11 underweight subjects, they were fed a complete formula exclusively through a vein nutrition and they were underweight and they were basically overfed with this nutrition. They were provided with excess calories. So predictably these subjects would gain weight.

[00:41:42]Now the researchers also meticulously collected the urine and feces of the subjects and they measured the excretion of nitrogen, phosphate, potassium, sodium, chloride and calcium. And because they knew the ratios of each of these nutrients within bone, muscle and fat, they could determine how much of each tissue was being formed in each subject.

[00:42:04]Now comes the twist. The researchers then selectively removed each of these elements from the infusate and they found that removing nitrogen, phosphate or potassium completely halted the formation of muscle. If they didn't have sufficient nitrogen which is a proxy for protein phosphate or potassium you cannot make muscle.

[00:42:30]When they removed phosphate and sodium, they prevented bone formation. And when they removed nitrogen, they reduced the bone formation by about 75%. And when they removed potassium by about 65%.

[00:42:43]So phosphate and sodium were clearly the most important for bone. But all four of these were incredibly important. And and we've shown this by research. The Women's Health Initiative showed that, you know, low sodium diets increase the rate of osteoporosis.

[00:42:58]Then what about fat?

[00:43:01]Now in the words of the researchers, an abundant supply of glucose was the only requirement for the enlargement of outpost tissues.

[00:43:11]So when bone and muscle can't be formed, the inputs that would otherwise go to lean tissue are instead directed into fat stores.

[00:43:22]And there's clinical randomized control trials to support these findings. This was a double blind randomized control trial published in 2015. And they supplemented subjects with phosphorus and they examined their weight gain and waist circumference. And the subjects who were randomly assigned to receive the phosphate lost weight in a significant amount and they also had improvements in their waist circumference, glucose levels and insulin levels. The only intervention here was giving them extra phosphate and they lost weight.

[00:43:58]Now just in this context here, I'd just like to briefly discuss the supernova study which most of you will probably be familiar with um which apparently concluded that ketogenic diets are bad for the bone. Well, understand that we know that you know micronutrients like potassium are very important for the bone. And if you realize that the subjects, the ketogenic athletes in this subject were actually deficient in potassium.

[00:44:24]their potassium intake was actually below the recommended diet daily intake levels. So this is a significant confounder. So it's simply implausible to attribute the ketogenic diet effects on bone when we've got we know they're in a potassium deficient state. So I'd just like to make that point. Which of the following is incorrect? Bone mineral density has been shown to increase secondary to nutritional intervention in post-menopausal females. That's a big claim. Protein comprises 10% of the dry weight of bone. Non-farmacological restoration of bone mineral density is not possible in post-menopausal females.

[00:45:10]Pharmacological inhibition of osteoclast activity results in an improvement of bone micro structure. And the correct answer is B or the incorrect answer rather is B. So protein scaffolding comprises about 30 to 40% of the dry weight of bone. And this is incredibly important because you need to understand if we look at bone, bone is basically mineralized protein. So we have hydroxy appatite that's packed in with other trace minerals uh in between the protein fibrals, but we need the protein. So if we're just supplementing solely with calcium and trying to build bone, then you can see the limitation of that then we need to if we want to build bone, we need to provide all the micronutrients which are involved in bone and that's what the previous uh TPN uh infusate study demonstrated quite elegantly.

[00:46:04]Now this was a randomized double blind placebo control trial. They took men and women over the age of 65. So this includes females who are menopausal and they randomized them to either vitamin D and calcium or a placebo and their bone mineral density was monitored. So vitamin D and calcium and what they actually found that overall supplementing with vitamin D and calcium reduced their losses of bone. Now this is logical because bone gets broken down to release calcium if we need calcium.

[00:46:36]So if you got more calcium coming in you reduce the body's need to break down bone. So, it makes sense that supplementing would reduce the decline in bone mineral density, but it doesn't give the ingredients you need to build more bone. But then the investigators did something particularly clever. They stratified the results based on protein intake.

[00:46:57]Um, and what they actually found was that the tersile consuming the most protein while also receiving vitamin D and calcium increased their bone mineral density in an elderly population which included post-menopausal females.

[00:47:15]So if you provide all the substrate that you need to make bone, even post-menopausal females can reverse osteoporosis.

[00:47:24]Now I'd just like to mention very briefly the pharmacological treatments for osteoporosis and I have seen some of these agents used to manage fractures in athletes and this is completely and utterly for the most part depending on the agent inappropriate. So we have drugs like bisphosphinates which actually inhibit osteoclast activity. You need to understand what is happening. We're getting an increase in bone mineral density because we're reducing the body's ability to break down bone.

[00:47:58]That's fine. But part of that breakdown of bone is actually normal and healthy.

[00:48:02]We we we know about bone coupling. We've removed the defective microtubercula that happen through stress fractures or what have you and replace them with new ones. Now the drug classes like bisphosphinates, they stop you breaking down bone so your bone mineral density goes up. Fabulous. But then we do see this increased risk of atypical fractures. The bone becomes more brittle. The quality of the bone is actually impaired.

[00:48:28]So any pharmacological intervention that reduces the removal that inhibits osteoclasts almost certainly impairs the quality of bone. So increased bone mineral density is not the same as better bone. Now there is one exception to this. Uh we have pulseed parathyroid hormone which we know if we give parathyroid hormone and pulse basis it can actually stimulate osteoplastic activity and I I think in certain circumstances and this is certainly not going to be a discussion on that but uh pulse parathyroid hormone can be in appropriate populations and effective treatment. Just be mindful of the way that it works to build the bone. it actually has to suck all of those micronutrients out of the blood to push them into the bone. And while it's doing that, it can actually adversely affect the levels of those micronutrients in the blood. And that can actually lead to symptoms. So you need to make sure that you've got adequate intakes, adequate supplementations going on if you are going down that track. And obviously there's a theoretical risk of cancer in pediatric subjects so on and so forth, but we're not talking about that now.

[00:49:39]When it comes to assessing cardiovascular risk with a lipid panel, there's a metric called the triglyceride to HDL ratio, which is far superior to other metrics when we're looking at absolute level of cholesterol or absolute level of LDL. The triglyceride to HDL ratio is a far superior metric in the assessment of what we call aogenic dysipidemia, which is basically saying is somebody likely to have a heart attack based on this lipid profile. So uh again you saw the what I talked about earlier with LDL and so on and so forth and all cause mortality. Now one thing to understand though is that I also gave you a question that demonstrated that low vitamin B12 levels can actually increase the rate of uh lipid synthesis LDL so on and so forth. So if you do see somebody with a good triglyceride to HDL ratio, that doesn't let them off the hook entirely if their cholesterol level is, you know, quite high, you know, getting sevens and eights and so on and so forth. And it's worth having a look at these underlying factors which we know can actually increase cholesterol levels. So we know for example an underactive thyroid you you mentioned that an underactive thyroid is associated with increased cholesterol levels deficiencies of what we call the methyl donor nutrients um B12 folate betane choline so on and so forth that is associated with increased levels of cholesterol in terms of things we know that hemocchromattosis um iron overload is associated with hyper triglyceridemia and even a hemocchromattosis carrier state you don't have to be homozygous you can be hetererozygous and still have borderline triglyceride. So, there's a lot to a lot to dig on, but this is not a lipid chute. So, we we won't do too much on that. But HBA1C is a is a lovely thing to do. Um, and that's really not done often enough. Uh, but just be mindful that HBA1C has some limitations. So, when we're looking at HBA1C, what is it?

[00:51:35]We got a red blood cell and it's got sugar attached to it, non-enzymatically attached to the red blood cell. So what two factors influence HBA1C levels? So are you able to give me one factor now that would increase somebody's HBA1C?

[00:51:52]>> Um I mean your concentration of red blood cells like anemia can change it and then also your blood sugar levels like your chronic >> blood sugar is the obvious one and you are absolutely correct about anemia but but that's more because of the lifespan of the red blood cell. If you got more sugar in the blood, more of it's going to attach non-enzymatically to the red blood cell. But what happens if your red blood cells are living for a lot longer, if because of a deficiency, they're just not turning over, then you'll get an exaggerated HBO1C reading? What happens if you've got a LIS syndrome homoysis and you've got a very short red blood cell lifespan, which by the way, you can assess, you can get a few for with something called reticular sites, the new red blood cells.

[00:52:33]>> Yeah. So >> that would lower than in that case like you get a a falsely reassuring HBO1C if you've got >> Exactly. Exactly. So my preference is to actually throw a continuous glucose monitor on people and with a doctor's letter that people can get a you don't need to be diagnosed as type 2 diabetic.

[00:52:52]You can get one with a doctor's letter and Freestyle or Abbott have a a deal on at the moment where the first one is only $15. And I think that's an absolutely beautiful thing for most people to do. Now you mentioned LFTs which is absolutely you know 100% correct. Um I I just want to talk briefly about the biochemistry of the LFTs. Um these are commonly misinterpreted. So there's two that we mainly look at. We we'll just put GGGT and ALP to one side. Alkaline phosphotize to one side. We'll just look at A and ALT. Now A is usually found in not insignificant amounts in scalletal muscle. So if you've ever got a rise in AST that's very suggestive that there could be a muscle problem and you'll also have a look at creatine kynise which is another intra intramuscular enzyme and you'll usually see that as and CK levels will usually track together ALT is much more preferential to liver itself but understand there's two possible causes for ALT being rise you can actually have herpatellular damage and you'll get that enzyatic leak which is you very predictable. Uh but it's also an enzyme that's associated in uh in energy well the dealing of pyuvate and if you have an energy excess from a high carbohydrate diet that can actually induce alt levels to increase. So I won't bore you with the biochemical mechanisms that just understand high alt may be a sign of early metabolic derangement and that's why we often see it elevated in pre-diabetes or diabetic states. Um it's not just hpatoscellular damage in the way that GGGT is an inducible enzyme. ALT is also an inducible enzyme. I would argue that if we look at the literature on all cause mortality, there's very little difference in all cause mortality in a systolic blood pressure of 140 to that of 120. And especially when we look at the the longer lived populations, if we want to establish longevity, we want to look at who who are living the longest.

[00:55:00]Well, you know, the the oldest people, there's no real difference in mortality with a systolic of 120 to to 140. I'm certainly not going to scare the patient and saying we're going to put you on blood pressure medications, you're going to die, so on and so forth. And we often gaslight our patients. We see patients get scared by these kind of numbers.

[00:55:19]Statistically speaking, 140 systolic is simply not that bad.

[00:55:25]But uh I think the glucose of 6.9 is what mostly concerns me. Do you have any thoughts on that?

[00:55:33]>> I think maybe more than this talk, but prior to today, I probably would have said no. I think it's still under the diagnostic criteria for sort of pre-diabetes or diabetes.

[00:55:42]>> Yeah.

[00:55:43]>> Absolutely. And we know this is pre-diabetes. I mean we can call it pre-diabetes. We even have another condition called pre pre-diabetes which we can talk about the mechanism of but basically it's a scale. It's a continuum. We often think about these things as dichomous variables. Um it's either good or it's bad. I mean these reference intervals really lend themselves to that. You're in or you're out. But if we actually look at the data, they're on a continuum. And this guy is certainly headed for bad health.

[00:56:11]And of his cardiovascular risk factors, the elevated glucose really stands out to me. And I would actually argue that somebody with pre-diabetes probably should be given exactly the same lifestyle interventions as somebody with diabetes.

[00:56:28]Now here's an interesting question and you may not know the answer and if there's anybody else who wants to chip in is what is the underlying pathophysiological cause or the likely pathophysiological cause of his glucose being slightly elevated at 6.9.

[00:56:49]Uh I would have thought it would be more of a type two diabetes pathways to sort of burning out of the insulin producing cells in the pancreas but be my thought.

[00:56:59]>> So >> is it due to insulin insensitivity?

[00:57:02]>> Exactly. Insulin resistance. So the insulin this gentleman has is in all likelihood not working properly. But that's not the full story because we know that in about 10 to 15% of adults diagnosed with type 2 diabetes, they actually have an autoimmune form.

[00:57:23]We can call it latent autoimmune diabetes of adulthood. And you have a combination of insulin not working probably. That's the insulin resistance combined with an insulin deficiency problem. And that's what you just referred to when you said the pancreas, the beta eyelet cells in the pancreas burning out. So this is almost certainly an insulin resistant problem. Um but we do need to try and get a feel for well is it possible that he could be one of these 10 or 15% who's you know failing to produce enough insulin because they need to be managed differently. If your insulin is not working properly, lifestyle management such as an appropriate reduced low carb, you know, low carbohydrate diet, exercise, so on and so forth can be absolutely fabulous.

[00:58:07]But if you're deficient in insulin and you've tried everything lifestyle and you've maxed that out and your sugar's still high, then you need to replace that insulin. There's no other two ways about it. And the best way to do this is with a modified oral glucose tolerance test. So we give people they have the 75 gram of glucose and we measure their their sugar level and at the same time we measure their insulin level because if we see that somebody in a type 2 diabetic will see the insulin level will be really high their pancreas is releasing the insulin but it's just not doing its job. But if you're going into this ladder latent autoimmune diabetes of adulthood you'll start to see the pancreas starting to fail. The insulin is actually inappropriately low.

[00:58:51]So it it's very important to try and get a feel uh for those two different cases there.

[00:58:58]So one of them insulin's not working.

[00:59:00]The other one is you just don't have enough insulin. And this this oral glucose tolerance test with insulins it can be done you can order it if you want is the most effective way of assessing for a deficient insulin secretion. Now just as an aside, we mentioned blood pressure earlier and you sort of mentioned or you alluded to essential hypertension which is just blood pressure that occurs. In actual fact, it's the action of insulin usually in a hyperinsulinemic state on the kidneys that drives essential hypertension. And nefrology doctors understand this very well. So you're probably familiar with the uh the the epithelial sodium channel, the enac channel in the in the kidneys that actually retain sodium. So this is what eldoststerone acts on.

[00:59:49]Well, insulin activates the same transporter. So we know that basically if you've got excess insulin acting on the kidneys that leads to excess sodium retention, it's the sodium retention that drives the blood pressure. So if you've got somebody, so if he's a bit mild hypertension, let's not start this chap on drugs.

[01:00:08]Let's have a look at his insulin and try and deal with his insulin resistance.

[01:00:13]And the fact that he's on a standard Australian diet really tells us he's probably on a crappy diet. His, you know, the the standard Australian diet is a is a very very low bar.

[01:00:25]This is a little complex. So the thing is apo lipoprotein B there's only one of them on on the lipoprotein and you have to understand what this actually measures. So when lipids get synthesized by the liver we've got the class very low density lipoprotein VLDL as that circulates and that donates its cargo it actually shrinks a little bit it becomes an intermediate density lipoprotein and it donates a bit more cargo and it becomes a low density lipoprotein. So, we've got these three particles that we talk about in medicine. And so, they're three different entities, but they're really like a deflating balloon. They're exactly the same thing. It's just lost a bit of content, lost a little bit of air. And each of those three particles actually contains the appo 100 moyote embedded within the membrane. So, when we're measuring an absolute B 100, we're not always sure which one of these we're measuring. And it is significant because LDL is actually we know the association of that with health is that it's actually probably better higher um whereas VLDL which is really how we assess triglyceride level that we don't actually directly measure triglycerides we just calculate it based on VLDLDL level um VLDLDL production which is driven by lipogenesis we know is actually associated with poor health. So there are some limitations and and you have to understand the underlying biochemistry and the physiology of how these lipids are generated. Uh in general it's ratios are better. Um so I certainly wouldn't look at a B 100 in isolation. Um but I generally feel if you're looking at a you know HDL to an Apo ratio that would be better or a triglyceride to HDL ratio. But understand that when you're looking at B 100 levels full stop, you don't really know everything that's making it up. You you can measure it, by the way. You can do something called a lipid electrofaresis. Um but that's over $100 and um you probably want to know how to interpret that before you order it. Now uh so what we've got here, we've got a a pretty common presentation. and we've got a 32-year-old patient and she's got gastrointestinal symptoms and they appear to be postprandial. So, what are your first thoughts? What what jumps into your head about this to start with?

[01:02:46]>> Uh, so my initial thoughts were just from the alternating diarrhea and constipation is a possible presentation of mixed mixed IBS quite young still.

[01:02:55]So, the key is you'd want to rule out um IBD. So um doing initial bloods and in particular a fecal cal protectin um is quite sensitive for IBD and inflammation in the in the gut and also >> let's just say first of all textbook straight up that's exactly how I would approach it. Um but let's dig down into these tests. I think we need to when we're ordering tests it's useful to understand what we're actually looking at. Fecal crotectin beautiful. So this is a measure of neutrfilic activity in the gut. Now not all inflammatory bowel disease is neutrfilic. We've got for example eenophilic esophagitis. We've got lympositic colitis on and so forth. So it is while it is very good and it is probably one of the most sensitive tests for inflammatory bowel disease. It's also useful to understand that there's potentially other types of inflammation within the gastrointestinal tract that feal culprotectin won't pick up because it is a neutrfilic based test. But anyway, sorry, carry on.

[01:03:58]>> Oh, no. That's a Yeah. So, I suppose like to help with that, you know, like the level would be important. So, greater than 150 I think it's nanogs from memory is the >> Yeah. Well, let's talk about let's assume that okay, you you're doing some excellent tests there. Um, you're probably also doing a celiac corology.

[01:04:15]Um, you're probably also doing nutrient levels because you want to make sure people with inflammatory bowel disease tend to have impaired absorption of nutrients.

[01:04:24]uh and we'll we'll come back and talk about that in a moment. But clinically in somebody's presentation, we know that inflammatory bowel disease is frequently associated with what we call the ceronegative spondaloarthopathies. And you you probably should all know the four subtypes of those at the moment.

[01:04:40]But there's so much overlap between them. I actually don't I don't find the clinical distinction or distinguishing between the those four groups particularly useful. But I know that people with joint pain, inflammatory joint pain, migratory joint pain, pain that's worth in the morning or after periods of immobility um frequently will have these inflammatory gut related issues. In terms of muscular scalletal manifestations, you want to ask for in particular buttock pain or alternating buttock pain. You also want to ask about enthalopathies such as um Achilles issues.

[01:05:15]>> Yeah, let's talk that that is a huge one. That is absolutely huge. So in my screen I don't always ask cuz sometimes people just accept things as normal. You you you press on each of the bony prominences the epicondiles around the elbow the back of the calccanous and the the plantto fascia insertion. By the way, plantto fasciopathy almost certainly is an autoimmune enthosopathy, which is probably why there's so many treatments being described for it that are largely completely ineffectual and why when you inject them with steroid, they'll get a temporary, but they will get a definite relief relief for a period of time. It's because it's the the immune system is doing a lot of the damage. So, if we suppress the immune system with a corticosteroid, you will get some benefit. So, you know, those kind of things. Do they get mouth ulcers? That's very common in Crohn's disease.