1/8 - Just gave a 30-min talk to 100+ conventionally trained doctors.
Asked 5 “controversial” nutrition questions BEFORE vs AFTER.
The mind-shift was staggering. Doctors aren’t closed minded - they just need to see the actual science.
Results below ↓ 2/8
Q1: “Dietary saturated fat is harmful to cardiovascular health” Before: 46% said True After: 3% said True, a reduction of 93!!
Seed oils are out and tallow is in.

All too often, there is a lack of nuance in discussions surrounding obesity and weigh loss. In this series of tweets, I address the core issues, while also touching on several important, yet overlooked topics. I suspect much of this content will be new to most conventionally trained doctors.

Understanding Obesity: The Role of Hormones and Nutrients

The Calories In/Out (Energy Balance) model of obesity is wrong

Imagine if you went to a doctor, and after assessing you, they said - ‘Of course you feel terrible, you have a fever of 40°C (104°F). All you need to do is bring down your fever and you’ll feel better’. Would you be happy? While this information is accurate enough, it is completely unhelpful, in that it doesn’t provide any advice at all on how to actually bring the fever down.

Patients attending doctors for assistance with weight loss often receive equally useless commentary. In line with the "calories in/calories out" model of obesity, they are simply told they need to expend more calories than they take in. The problem is, they are often not given any advice on exactly HOW to do this. And when they are given advice, it is often completely wrong. Many doctors advise patients to restrict fat intake, primarily on the basis that it is more energy dense than either protein or carbohydrate.

The problem is, the Calories in/Calories out energy balance model of obesity completely ignores the sciences of biochemistry and endocrinology, overlooking differing effects of fat, protein and carbohydrates on hormones. By oversimplifying the cause of obesity to a simple case of caloric balance, incorrectly presumed to be entirely under volitional control, obesity is thought to represent a failure of will power. In essence, the implication is that most obese individuals are lazy and overindulgent, something that is both manifestly false and an egregious form of medical gas-lighting. The truth is, low fat foods, which typically contain large amounts of carbohydrates, have been scientifically proven to cause weight gain.

It's not however, that doctors give poor advice maliciously. Many doctors after all, follow their own advice, which may explain why in 2015, nearly 60% of Australia’s doctors were overweight or obese.

Hormonal Influences on Weight Gain
Most people are aware that thyroid hormone helps to regulated our metabolism, and that deficiencies can result in weight gain. The fact is, there are at least a dozen hormones whose dysregulation has been associated with weight gain. For example, high cortisol levels as seen in Cushing’s syndrome may lead to distinctive fat deposits known as "moon face" and "buffalo hump." By far the most significant obesogenic hormone, however, is insulin.

Insulin and obesity
A 1996 study conducted in Bogalusa, Louisiana, highlighted the crucial role of insulin in obesity . Over an 8-year period, the study measured insulin levels in children and young adults. It found that those with the highest insulin levels (in the top 25% at both the beginning and end of the study) were 36 times more likely to become obese compared to those with the lowest insulin levels (in the bottom 25%). Specifically, the risk of becoming obese was just 2% for those with the lowest insulin levels, while it soared to 72% for those with the highest insulin levels.

Type 1 diabetics well know that fattening effect of insulin. Before they are diagnosed, and commence insulin therapy, many type 1 diabetics are dangerously underweight. The reality is that, without insulin, the body cannot store fat. The commencement of insulin therapy can rapidly reverse this emaciation, research showing that type 1 diabetics gain an average of 5.1kg (11.2lbs) during their first year of insulin therapy . Despite its life saving potential in type 1 diabetics, up to 60% of type 1 diabetics may deliberately reduce or skip insulin doses due to its fattening effect – a condition referred to as diabulimia .

Further evidence of insulin's fat-storing effects is the development of localised fat masses at sites of injection. Known as lipohypertrophy, this can occur in anyone who injects insulin, one study reporting that 49% of all insulin injecting type 2 diabetics developed lipohypertrophy . *

*Importantly, many adults diagnosed with type 2 diabetes may actually have an autoimmune form that impairs insulin production. This condition, known as Latent Autoimmune Diabetes in Adults (LADA), is present in about 10% of diagnosed type 2 diabetes cases. Individuals with LADA are often more slender than typical type 2 diabetics and may even be underweight. While a strict low-carb diet is generally beneficial for these individuals, insulin therapy is often necessary. How insulin stores fat
From a biochemical standpoint, insulin has several key functions with respect to fat cells. Firstly, it facilitates both the uptake of glucose and fatty acids, converting them into stored fat known as triglyceride. Without insulin, glucose and fatty acids quite literally could not enter the fat cells to be stored. Recall the type 1 diabetic patients with deficient insulin levels who often present wasted and emaciated.

Secondly, insulin suppresses fat metabolism. For fat to be burnt for energy, the triglyceride fat stored in the fat cell first has to be broken down. Insulin blocks a key enzyme needed in this process, thus inhibiting fat burning. Understanding these actions of insulin helps to explain why, in the setting of high insulin levels, someone might have trouble burning fat. It has nothing to do with being lazy or not, this hormone can simply block fat burning.

Carbohydrate induced insulin release
Understanding the key role that insulin can play in fat storage, helpful advice from a doctor on how to lose weight could include information on how to control insulin levels. The most significant factor at play here relates the composition of food consumed, in particular, carbohydrate content.

Of the three macronutrients contained in food, carbohydrate, protein and fat, carbohydrates stimulate the most insulin release, followed by protein, then fat. Perversely, the advice to consume low fat and high carbohydrate food as promoted by the oversimplified energy balance model of obesity, has been scientifically proven to result in weight gain.

One researcher who has grasped the importance of insulin in obesity is Dr. David Ludwig, an endocrinologist from Boston. Similar to myself, his perspective on obesity has evolved over time, moving away from the traditional calories in/calories out model that we were both taught at university to a more nuanced understanding that includes the crucial role of the hormone insulin. Dr. Ludwig and his team conducted a study with overweight and obese young adults who had lost 10-15% of their body weight. Their energy expenditure was then measured while they followed either a high-carb or low-carb diet.

To avoid confounding, it was important that the subjects maintain a stable weight during this part of the study. However, maintaining weight stability in the low-carb group proved challenging—they had a tendency to continue losing weight. The researchers eventually had to feed the low-carb group more food to keep their weight stable, and ensure a fair comparison with the low-fat group.

The reason for this extra food in the low carb group became is clear when the subjects’ energy expenditure was measured. Participants on low-carb diets were burning an extra 300 kilocalories per day compared to those on low-fat diets. Of course, not every subject allocated to the low carb group was strictly low carb. When the analysis of energy expenditure was repeated based on what diet the subjects were actually following (rather than just what group they were assigned), the difference in calories burnt increased to 478 kilocalories per day - all without exercise. The low carb group was essentially getting a ‘free lunch’ the difference in energy expenditure being more than that expended by an hour bike riding .

Ludwig’s study elegantly demolishes the calories in/calories out model, proving that the ‘what’ at least as important as ‘how much’ when it comes to eating for weight loss. Foods releasing more insulin, namely carbohydrates, being more likely to cause obesity.

Excess glucose and lactate
Scientists have known for decades specific details in how the body metabolises carbs and fat. In a study published in 1975, subjects receiving all their nutrition directly into their circulation via a vein were provided either a high glucose or high lipid (fat) solution. All subjects received equivalent protein as per body weight .

The lipid-based group exhibited significantly lower insulin levels compared to the glucose-only group. This aligns with expectations, as insulin—a hormone that promotes glucose uptake and fat storage—is less stimulated when dietary carbohydrates (glucose) are minimal. Consequently, free fatty acid (FFA) levels were higher in the lipid group, indicating that fats were being mobilised and metabolised rather than stored.

Additionally, elevated ketone levels in the lipid group confirmed that fat metabolism was driving ketogenesis (ketone production). In effect, these subjects were on a ketogenic ‘diet’.

In contrast, the glucose-only group showed signs of metabolic stress. Blood lactate levels, often associated with the burning sensation during intense exercise, were significantly higher. This is due to glucose being able to readily overwhelm the ability of mitochondria (the powerplants of our cells) to process it. Glucose unable to be metabolised with mitochondria is instead metabolised through a less efficient system known as glycolysis, producing lactate as a byproduct. The fact is, only glucose metabolism can produce lactate. Fatty acid and ketone metabolism, occurring readily within mitochondria, does NOT produce lactate. (In this respect, fasting lactate level can act as a surrogate marker for ketoadaptation).

Overwhelming experimental evidence
Studies comparing low carbohydrate and low-fat diets for weight loss overwhelmingly come down in favour of low carb. The Public Health Collaboration of the United Kingdom has identified all randomised controlled trials performed since 2018 comparing low carbohydrate and low-fat diets . To date, there have been 71 randomised controlled trials over this period. Not one single study found statistically significant benefit in terms of weight loss in favour of low-fat diets. 0 out of 71 studies. On the other hand, 39 of the 71 studies found statistically significant evidence of superior weight loss in the low carb groups. This really should sound the death knell to the Calories in/Calories out model of obesity, and its associated recommendation to avoid dietary fat due to its caloric density.

Introduction to insulin resistance
There are other factors that influence the degree of insulin release. One of these is something called insulin resistance, where insulin ceases to function as effectively. This isn’t a problem with insulin itself, but rather the receptors with which insulin interacts. These receptors, especially those in muscle and the liver, stop responding as vigorously to insulin. Insulin resistance therefore, refers to a problem with insulin receptors, and not insulin itself.

Of course, insulin serves several important roles in the body, including ensuring glucose levels don’t get too high. Consequently, in a state of insulin resistance, the pancreas typically increases release of insulin, resulting in high insulin levels. secretes , the body doesn’t take this lying down, typically secreting more and more insulin to compensation for the relative ineffectiveness of insulins action. This is why insulin resistance is typically (but not always), associated with high levels of insulin.

Given that the insulin receptors on fat cells are less affected by insulin resistance than those on muscle and liver cells, the resulting high level of insulin results in excess activity of insulin on fat cells, both driving fat storage and inhibiting fat metabolism.

Fructose and insulin resistance
Sucrose, or table sugar, is composed of two simple sugars, glucose and fructose. In terms of insulin resistance, fructose is particularly problematic. While glucose can be stored both in muscle and liver tissue for use at a later time, there is no such reservoir for fructose. Consequently, fructose can strongly drive the process of de-novo lipogenesis (DNL), producing fatty acids from fructose. There are several regulatory steps in the metabolic pathway which means glucose does not activate DNL anything like fructose does.

The primary fatty acid produced by DNL is palmitic acid, a saturated fat. ** Palmitic acid can then be converted through a series of steps into a waxy type of fat called a ceramide. This is especially important, as ceramides are known to be a CAUSE of insulin resistance. The ability of ceramides to cause insulin resistance relates to their ability to be taken up by particular regions of cell membranes known as lipid rafts. It is the lipid raft regions of cell membranes that house insulin receptors. Accordingly, incorporation of ceramides into lipid rafts can disturb the function of insulin receptors. This is a major cause of insulin resistance.

**Elevated circulating levels of palmitic acid are associated with metabolic diseases such as diabetes. De-novo lipogenesis is the major source of these fats, direct contribution from saturated fats being relatively insignificant. Consequently consumption of fructose containing sugars is much more significant in increasing the levels of this saturated fat in the blood than the consumption of saturated fat itself.

Seed oils and insulin resistance
Seed oils are essentially a repurposed industrial waste product. Indeed, the refinement of cottonseed oil into Crisco, as detailed by U.S. author Nina Teicholz in her book "The Big Fat Surprise", was a landmark event where through a mix of marketing and endorsement by the American Heart Association, a byproduct of cotton production entered the food supply at scale.

The ability of seed oils to contribute insulin resistance relates to their containing a plant derived analog of mammalian cholesterol known as plant sterols or phytosterols. Plant sterols are structurally similar to cholesterol, allowing them to compete with cholesterol for absorption.*** Accordingly, some plant sterols may be absorbed, and subsequently converted into ceramides. Thus the mechanism by which both fructose and seed oils contribute to insulin resistance is near identical. While the levels of plant sterols are highest in seed oils, they may also be found in other plant derived oils, including olive, coconut and avocado oils#.
*** Accordingly, plant sterols may have a ‘cholesterol lowering’ effect, despite which, there is no credible evidence that they offer any mortality benefit in those with heart disease.
#A study performed in collaboration with the BBC’s "Trust Me I'm a Doctor" series investigated the effects on ‘cholesterol’ of different dietary fats, including olive oil, coconut oil and butter. The saturated fat content was coconut oil - 94%, butter – 66% and olive oil 19%. In terms of plant sterols, olive oil tends to have higher levels than coconut oil, with butter having none. If it is true that saturated fat increases cholesterol, then the largest increase would be expected with coconut oil. If on the other hand, it is plant sterols that cause a reduction in cholesterol, the largest drop would be seen with olive oil followed by coconut oil. Indeed, coconut oil was found to actually lower ‘LDL’ levels, in a direct repudiation of the diet heart hypothesis.

From a historical context, the earliest paper I am aware of citing a direct link between the consumption of seed oils and insulin resistance is a 1965 study where some subjects received a daily 80g supplement of corn oil. Two patients were removed from the study because of diabetes. One subject not known to have diabetes began to urinate glucose (glyucosuria) after starting the oil supplement, and was subsequently diagnosed with diabetes through an oral glucose tolerance test.

Another subject with known mild diabetes noted a considerable increase in the degree of glucose in his urine. The researchers then performed something of a crossover with this patient, first stopping the oil supplement, after which the glucose in his urine disappeared. He then restarted the oil supplement, and ‘heavy’ glycosuria was noted to return, after which the corn oil supplement was stopped for the final time . ##

##Despite this dramatic description, very little research has specifically looked at the benefits of seed oil elimination (there are of course, numerous studies that look at the combined intervention of lowering sugar and seed oils together, invariably with positive results). Nonetheless, there are several studies which provide clear evidence of harm of INTRODUCING seed oils into the diet. Four major RCTs have examined the effects of replacing saturated fats with seed oils, and all have found negative outcomes.
•The Rose Corn Oil Trial (1965) reported an 86% increase in heart attack risk and a 364% increase in mortality among participants consuming corn oil.
•The Minnesota Coronary Experiment (1968) found that while plant oils successfully lowered LDL cholesterol, they were associated with a 22% higher mortality risk per 0.78 mmol/L reduction in LDL.
•The Sydney Diet Heart Study (1978) showed a 62% increase in mortality when saturated fats were replaced with plant-based oils.
•The Women’s Health Initiative (2006, with follow-up in 2017) found that substituting saturated fats with plant-based products led to a 26% increase in cardiovascular complications in the initial study, which later rose to 61% in the follow-up.

The point is, seed oils have never been proven to be safe, and there is very good evidence they are likely to be harmful. Their widespread infiltration into our food supply is nothing short of a travesty. It is ironic that calls for their reduction in the food system are typically met by claims that there is insufficient evidence to justify this move. Completely ignoring the fact there was never any evidence to support their inclusion in the first place.

Thyroid hormone
Insulin receptors are not the only receptors that reside in lipid rafts, another being the receptors for thyroid hormone receptors. It follows that ceramide induced lipid raft disturbance that is capable of disrupting insulin receptor function is likely to also impair the function of other embedded receptors. With respect to thyroid hormone receptors, this likely explains the significant association between type 2 diabetes, a disease of insulin resistance, and thyroid hormone resistance . Further, this is consistent with research findings that ketogenic diets low in fructose and seed oils, improve both thyroid hormone and insulin sensitivity .

I often write short summaries on various topics that I give to my patients. This is what I have just composed for Nattokinase.
Nattokinase is a natural enzyme capable of degrading fibrin, a key component of blood clots. It is derived from natto, made from fermented soybeans. While research on nattokinase remains limited, some evidence suggests that daily doses exceeding approximately 4,000 FU may aid in the management of atherosclerosis.

Second study in a week finds seed oils linked to cancer. Men with prostate cancer consuming the most seed oil had more aggressive tumors. With ~40% of cases under surveillance (no active treatment), this could be huge. We need more research on seed oil & cancer links NOW! This was a prospective randomised observational study - gold standard for epidemiology.
Time for some of the billions of $$$ being spent on genetics of cancer research to be invested in funding randomised controlled trials of seed oil elimination.
ascopubs.org/doi/abs/10.120…

1/5 - Thanks to @Mangan150 for sharing this historic article demonstrating that urinary ketones may be useful in the treatment of UTI.
Interestingly, this research found that urea does not have significant antibacterial activity, in contrast to a more 'recent' 1968 study.

https://twitter.com/Mangan150/status/999056736337051648

2/5 - Given I am seeing more and more patients with symptoms of chronic UTIs non responsive to standard antibiotic regimens, it would be good to know which factor is most important - ketones or urea. Specific dietary recommendations could then be provided for either.

UTI's are often undiagnosed - patients (usually female) with symptoms of UTI's are often dismissed because they have normal urine cultures.
One study found urine culture missed 67% of all known urinary pathogens. Furthermore, even identified pathogens are commonly discounted if the bacterial count is <100,000 bugs per millilitre, which might simply happen if you are well hydrated (or the bugs are very effective at clinging to the wall of the bladder - which many are).

1/6 - Dupilumab is approved to treat severe eczema $$$(~$22,800 AUD/year) and works by blocking the cytokines IL-4 and IL-13.

These cytokines have been implicated in various autoimmune diseases including rheumatoid arthritis and have been shown to be elevated by cow's milk. 2/6 -This may be why the meat and dairy consuming Masai have been found to have high rates of RA (if wondering about raw dairy, consider the Masai consume milk from the cow).
I suspect many patients prescribed this drug will not be first recommended a trial of dairy elimination.

HbA1c can rise despite a lowering of blood glucose.
This can occur when blood cells live longer, meaning they are in contact with glucose for longer.
Reticulocytes indicate RBC lifespan.
When haemoglobin is stable, lower reticulocytes indicate a longer RBC lifespan.
1/4 Reticulocytes are 'new' red blood cells. When RBC numbers are stable, few new red blood cells demonstrates a longer lifespan.
Use of a continuous glucose monitor can provide further reassurance that glycaemic control has not deteriorated.
2/4

Don't think that fruit is natures candy.....you'll find this study interesting.
80 subjects were randomised to ≥4 or <2 servings fruits/day.
After 6 months, the fruit rich group was fatter, had more liver fat, more liver damage, higher blood sugar and more insulin resistance. Those on the fruit rich diet gained on average 7.0kg over the 6 month period, while those on the reduced fruit diet lost 6.5kg.
pubmed.ncbi.nlm.nih.gov/35710164/

Both statins and aluminum have been associated with neurodegenerative diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis and neuropathy.

The association between aluminium exposure and neurological disorders has been known since at least the 1970’s. A 1976 study with found dialysis patients who died with dementia symptoms had brain aluminium levels 10x's greater than controls.

Papers published In 1978 described how kidney patients on dialysis developed dementia when the aluminium in local water supplies was increased.

The WHI study provides a clear challenge to the lipid hypothesis - those with a history of CVD randomised to reduced fat diets had an increased risk of dying (while also using more statins). I challenge those who promote low fat diets and the use of statins to explain this. Those with normal blood pressure had no statistical difference in mortality - they did however record a reduced risk of non fat heart attack on the low fat diet. This was offset by increased risk of stroke, which MAY more adversely impact on quality of life.

Ever been told no RCT's show any harm of replacing saturated fats with seed oils. Three large RCT's have found exactly this. Their findings were misrepresented to the public.
1) Sydney Diet Heart Study
2) Minnesota Coronary Survey
3) Women's Health Initiative Sydney Diet Heart study (1966-73). Replaced saturated with polyunsaturated fat post heart attack. Data published 40 years after completion following investigation by Chris Ramsden - displacing saturated fat in the diet with polyunsaturated fats led to a 62% increase in mortality.

Hey @kevinnbass, you've now had time to review my book chapter. Given you appear to still be of the opinion that saturated fats are bad, it's now time for you to put up your evidence...and explain why the papers I referenced are wrong.
@FatEmperor @SBakerMD @KenDBerryMD @DaveKeto @kevinnbass, as a subject matter expert who is clearly confident in his own opinion, you have probably already read the papers I cited - shouldn't be too onerous for you to critique.