Editor's Note: This article is a reprint. It was originally published May 21, 2023. Some of the dietary figures in it reflect positions held at that time. Where they differ from current guidance, the current guidance is noted in the text.
In this interview, Georgi Dinkov and I discuss diet, diving into some of the finer details that can make or break your health. Dinkov is a student of Ray Peat, who passed away around Thanksgiving 2022, leaving behind a legacy of iconoclastic wisdom on how to optimize biological health.
For example, a ketogenic diet can be very useful initially when transitioning people who are metabolically inflexible, which Dinkov believes describes most Americans. Indeed, national data suggest poor metabolic health is widespread: as of 2017–2018, only 6.8% of U.S. adults had optimal cardiometabolic health.1 So, in the short term, most people can benefit from going keto. However, if you continue in ketosis long term, you could run into problems.
Elevated Cortisol Leads to Central Obesity
As just one example, while weight loss is a typical response when going on a ketogenic diet, months later, maintaining that weight loss often becomes a struggle again. Dinkov experienced this firsthand. Once he started following Ray Peat's recommendations, he lost the weight again and kept it off.
"My take is it's an endocrine problem," Dinkov says. "So if you're struggling with weight you cannot lose, I think it's a good idea to do a blood work [panel] for the steroids … Every single person that has been struggling with excessive weight that has emailed [me] their blood results, without exception, their cortisol is either high-normal or above the range, both the AM and the PM value.
Their thyroid is less than optimal, in fact, pretty bad for most people … They're at the upper limit of normal. A very large number of people are basically hypothyroid … I think we are eating foods that are lowering our metabolic rate. We're living an excessively stressful lifestyle.
That's probably not a surprise for anybody. Many people think, well, stress is good for you. It's good as a hormetic response in an acute situation, but not when you have chronically elevated cortisol…
One of the defining features of elevated cortisol is that you have central obesity. So that, to me, is really the problem. We have higher than desirable levels of stress, suboptimal diet, and we're surrounded by a number of different endocrine disrupters …Most of those are found in plastics."
Why I Changed My Mind About Low-Carb Diets
One of the foundational concepts of health that I've had to radically revise my thinking on, based on the work of the late Ray Peat and his student Georgi Dinkov, is the idea that eating a low-carb diet long-term is the best way to optimize your metabolic and mitochondrial health.
I now realize that this was misguided, and the reason for that has to do with the fact that your body requires glucose and will not let blood glucose fall to a dangerous level if it can help it. The main safeguard is the hormone cortisol, which turns out to be the problem.
In medical school, we learned that cortisol is a glucocorticoid. Gluco means glucose (sugar) and cortico means it comes from the adrenal cortex. It's also another word for steroid. We were told that cortisol is responsible for maintaining glucose homeostasis but led to believe its primary purpose was for inflammation.
Well, that's just not true. While cortisol certainly contributes to glucose balance, its primary purpose is to raise your blood sugar when it is too low and you don't have enough glycogen reserves in your liver.
How Does Cortisol Work?
But just how does cortisol increase your blood sugar? It does it by breaking down your muscles, bones, and brain. It sacrifices your lean muscle mass to release amino acids that your liver converts to glucose in a process called gluconeogenesis.
So, ultimately, cortisol also is going to cause inflammation and impair your immune function. And it increases food cravings. So, you do not want your cortisol to be elevated. For a long time, I was a proponent of a low-carb diet, but now I realize that chronic low-carb is not a good idea.
As a fuel, glucose is vastly superior to fat, and this was something I simply got wrong. The same thing goes for fasting. Both low-carb and fasting are great interventions in the short-term for those who are overweight and metabolically inflexible.
However, once you've regained your metabolic flexibility, it is important to revise your strategy and add healthy carbs back in, or else these strategies will backfire and lead to decreased metabolic health, compromised mitochondrial function, and impaired metabolism.
Cortisol is highly catabolic — chronically elevated levels break down body tissue, and that pattern is associated with accelerated aging. To stay healthy as you age, you need to be anabolic and build healthy tissues like muscle and mitochondria. Elevated cortisol will seriously impair those efforts.
Important Cautions Before You Increase Carbs
So, it is clear that you need to be doing everything you can to keep your cortisol levels and chronic inflammation low. But it would also be a major mistake to increase your carb intake if you are still on a high-fat diet. I did this experiment in the mid-80s after I read the book by Harvey and Marilyn Diamond called Fit for Life.
They suggested having fruit only for breakfast, which I tried. Then I did my lab work and found my fasting triglycerides and lipoprotein profiles had exploded for the worse. I prematurely concluded that a high fruit diet was nonsense and remained relatively low carb for nearly four decades.
This was until I encountered Ray Peat's work and reevaluated my initial impression. I now understand that I was missing important parts of the strategy. Now I frequently eat 3 to 4 pounds of watermelon (without the rind) at 5:30 as my first meal, followed by three eggs and 8 ounces of white rice and 2 ounces of maple syrup one to two hours later.
That sounds like a lot of carbs, and it is. I have additional fruits later in the day and now my carb intake is about 475 grams a day and comprises about 60% of my daily calories. You might wonder what has happened to my weight and blood sugar with all these extra carbs.
Well, I thought my weight was good at 192 as I increased my muscle mass, but it has decreased by 10 pounds to 182 with no change in muscle mass. My fasting blood sugar has dropped 10 points. So far it seems to be working for me. To be clear, this is my personal experience over a short period — not a study. And 475 grams is well above the roughly 250 grams a day that suits most adults — more for those who are very active, like myself. I recommend treating it as an illustration of the direction, not as a target.
The Vital Metabolic Switch You Need to Understand
This is one of the most important principles in food science that I never learned or understood until later. My strong guess is that this is also true for most natural medicine clinicians. Low-carb diets have helped at least tens of millions of people improve their health for a very good reason and that is there is a stealth switch that controls what fuel your mitochondria can burn as they can only burn one fuel at a time, either fat or glucose.
The switch has been given the name the Randle Cycle, but it is more helpful to visualize it as a railroad switch that changes the tracks of the train, and the train can only travel down one track not both. This is because only one type of fuel can be burned at a time.
The best-case scenario is you metabolize, or burn, glucose in your mitochondria without any reductive stress When you do this, you will only generate 0.1% reactive oxygen species (ROS).
Not only does this route generate less ROS but is also incredibly efficient at energy production by creating roughly 30 to 32 ATP for every molecule of glucose that is metabolized.2 It will also generate metabolic water and carbon dioxide, which are important for health.
For this to occur you will need to consume less than 30% of your calories as fat. When you consume significantly more than that amount the switch changes to burn fat in your mitochondria and you will not be able to burn glucose until your fat decreases to less than 30% of calories.
Since glucose is unable to be shuttled into the mitochondria to burn it winds up backing up into your blood stream raising your blood sugar. In the bioenergetic framework, this is understood as a contributor to the insulin resistance that precedes Type 2 diabetes. What little glucose is burned for fuel is done by using glycolysis which is a primitive pathway that bacteria and cancer cells use.
It is great we have this pathway as you absolutely need it for quick fuel when you are activating your type II muscle fibers. But if this is the primary way you burn glucose you are in a catastrophic metabolic state as you are creating loads of lactic acid as a waste product instead of healthy CO2, and you are only generating 2 ATP for every molecule of glucose, which is roughly 93% less energy.
Lactic acid increases reductive stress, which drives reverse electron flow in the mitochondria and raises reactive oxygen species production. Reverse electron transport at complex I is a recognized high-output route for superoxide, though published estimates of how much total electron flow ends up as ROS vary widely by tissue, substrate, and oxygen tension, and no single figure is well established. Reductive stress — the opposite of oxidative stress — is covered in more depth in an interview with Brad Marshall.
How High-Fructose Corn Syrup Causes Disease
One factor that makes a big difference in your metabolic rate is the type of sugar you consume. Contrary to popular belief, there's a dramatic difference between high-fructose corn syrup and cane sugar. They're really two different foods. If the high-fructose corn syrup is properly processed to remove all starch, then it's very similar to cane sugar because it's about 55% fructose and 45% glucose.
Most people who embrace natural health believe sugar is a pernicious evil, but Peat's and Dinkov's position is that the negative effects are primarily caused by high-fructose corn syrup, and that pure cane sugar can actually be a useful strategy to counteract some of the challenges that people can get into when on a strict low-carb diet. Dinkov explains:
"Cane sugar, if it's pure, has a very different overall systemic health effect than high-fructose corn syrup … I think most of the sugar sold in the crystal form, especially organic ones, is pretty safe. Heavy metal contamination used to be a problem in sugar distillation but it looks like most of the western countries have sorted this out.”
Dinkov points to research showing honey raises blood glucose less than an equal dose of pure glucose,3 and to a 1983 study in which rats drinking sucrose-sweetened cola ate about 50% more calories without excess weight gain.4 He continues:
“So sugar is not dangerous. It's perhaps the only nutrient that we evolved to metabolize for fuel. But the other two micronutrients, even though we can metabolize them as fuel, come with a lot of strings attached …
If you're oxidizing PUFA [polyunsaturated fat], then all hell breaks loose. If you're oxidizing saturated fats, it's far less dangerous. But in the long run it still puts you, due to the Randle cycle, into the semi-diabetic state because it decreases your insulin sensitivity.
So pure sugar is what we are meant to oxidize for fuel. If you get it from ripe fruit, great. If you can get it from [raw unadulterated] honey, probably just as good if not even better. But if not, then the pure white variety, preferably organic, that you get from the store, I think is a very good source of most of the carb calories that you intend to eat throughout the day."
The Glucose-Cortisol Link
In my book "Fat for Fuel," I argued that healthy saturated fats generate fewer free radical species in the electron transport chain than sugar. However, I've revised my views on this, based on Peat's work.
The problem is that if your glucose level is low because you're on a low-carb diet, your body is going to compensate by self-generating glucose, and that stimulus to make glucose is part of the obesity puzzle, because one of the ways in which your body produces glucose is by secreting cortisol.
And, as explained by Dinkov, if your cortisol is chronically elevated, you end up with central obesity and chronic inflammation, which clearly isn't good. So, you've got to have a certain amount of glucose, and it's best to get it from your diet rather than forcing your liver to make it, as cortisol is then also being churned out. Dinkov explains:
"If glucose is oxidized properly going through the Krebs Cycle and electron transport chain, it generates more carbon dioxide per molecule of glucose oxidized than do fats.
Now, carbon dioxide has this kind of controversial role in medicine. It used to be considered a metabolic byproduct that could be dangerous. People with chronic obstructive pulmonary disease have higher than normal levels of carbon dioxide in the blood.
But then, medicine started to look into this more closely, I think, over the last 10 years, outside of Dr. Peat’s research, and said, 'Hm. Carbon dioxide seems to have a lot of positive effects in the body.' One of them is vasodilation.
So basically, if your metabolism is not working properly, if you're not oxidizing glucose properly, you're not going to produce sufficient amounts of carbon dioxide. What happens then? Vasoconstriction. And since that is actually a problem, it raises blood pressure and all kinds of other things; all hell breaks loose. The body then releases an emergency vasodilator, known as nitric oxide. And that is now acquiring a bad reputation...
So, if you're not eating enough glucose, your body will make it. And, in fact, the primary evolutionary role of cortisol, the acute role, is actually preventing blood glucose from dropping too low, because that will put you into a hypoglycemic coma.
In the longer run its secondary role is to dampen down inflammation. So really, the acute, the lifesaving role of cortisol on a daily basis, is to prevent you from dropping into a coma because your blood glucose went too low.
But we don't want that process because it's going to get the glucose from the tissues. So, we need glucose [in our diet]. I think even the ketogenic proponents are now getting to the point of saying, 'We cannot be always in ketosis.' In the long term, it's not good."
Will Sugar Feed Cancer?
Ketogenic diets have also been hailed for their ability to prevent and treat cancer, but even this may turn out to be a misunderstanding in the end.
"I think some of the ideas around glucose feeding cancer stem from two basic misunderstandings," Dinkov says. "One is that cancer is an evil cell, genetically mutated, and that your only chance is to kill all of those cells because they're not going away by themselves.
First of all, that's not true... It's the metabolic derangement that happens first and, over time, this triggers the genetic mutations, because the cell, being in an energetic deficiency, cannot properly maintain its structure …
So what we need to be doing here is not trying to kill the cancer cell, because it is not a cancer cell. It is actually a normal cell that is metabolically deranged.
If we could compare it to anything, it'd be a diabetic cell [and] diabetes is now known to be caused by hyperlipidemia — too much fat in the body, too much fat in the blood. Basically, the cells are getting stuck in oxidizing fats, due to the Randle cycle.
And then, the glucose that's floating around in diabetes, a good portion of it — because it cannot be metabolized — is being peed out … or you're converting it into lactic acid...
We are seeing an abnormal rate of fatty acid oxidation, because the cell is stuck in the cycle due to oversupply of fat.
The glucose, the 'cancer cell' cannot actually metabolize it, but because the cell needs its glucose for a variety of purposes — not just synthesizing energy, but also synthesizing DNA and RNA, and those two … can only be synthesized from glucose, not from fats — the cancer cell says, 'Oh, I'm in a state of extreme deficiency of glucose. Give me more.'
So, it increases the synthesis of these glucose transporters known as GLUT1 through GLUT4. Basically, that's why when you give a patient with cancer a little bit of radioactive sugar, it accumulates mostly into the tumor, because the tumor has a much higher capacity for uptake of sugar.
However, and this is the key difference, it has a much lower capacity for oxidizing that sugar. So, you’re going to see a lot of radioactive sugar accumulation in the tumor, but most of it will get converted to lactic acid…
And I think we already agreed that excessive oxidation of fat is a stress state. Right? We don't want to produce lactic acid, and as long as we are over-oxidizing fat, we will be producing lactic acid, and we will be uptaking more glucose …
There's only really two macronutrients that can go to the cell. Assuming cancer is a metabolic disease, and assuming a cell can only oxidize fat or sugar, then if it's not the sugar, it's got to be the fat. There's nothing else.
And if it's not the mutations; if the mutations are secondary to the metabolic derangement, it's got to be one of these two macronutrients that we can manipulate to actually try to cure the cancer. They already tried glucose restriction … That did not cure cancer. It did have a sensitizing effect to chemotherapy, but it did not result in actual cancer remission.
So now we're back to the other micronutrient, restricting the supply of fat. [S]tudies have tried doing low-fat diets for cancer, and are getting actually good results. Not cure, but good results."
One note for context:
The idea that metabolic derangement precedes rather than follows mutation is a serious hypothesis under active investigation; it’s not the settled position of the field.
It’s not a reason to decline, delay or stop cancer treatment. Anyone with a cancer diagnosis should make treatment decisions with their oncology team.
The Devil in the Details
Here, I'd like to share a personal story. In an effort to adopt this new knowledge, I increased my carbohydrate intake to about 250 grams to 300 grams, depending on the day and the fruit availability. When I got my blood work back, I was surprised to find my triglycerides were in the low triple digits, just over 100, which is abnormal.
Normally, I'm closer to 50. In my clinical experience, elevated triglycerides is almost always related to excessive carbohydrate intake, which seems to conflict with what Dinkov just explained. But here's the key: When you increase carbohydrates, you also have to lower fat. If you don't, you could end up with complications, as just happened to me. So, now I'm lowering my fat intake. Dinkov confirms my experience:
"Most of the animal studies say, 'High sugar diet causes this. High sugar diet causes that.' But if you look at their diets, these animals are already on a high-fat diet. All they did was add more sugar on top of it. Well, of course, in a situation like that, you're going to have an increase in the triglycerides, increase in LDL cholesterol, because the body can synthesize cholesterol from the sugars.
So, you're going to get these biomarkers associated with cardiovascular disease to increase, but it's actually not really a fair comparison. What you should be doing is keeping the diets isocaloric, the same. And also, not increase the total amount of calories, just replace some of that fat with sugar …
Another thing that is probably important is that since there's always some baseline lipolysis going on, when you're increasing the carbohydrate intake, the excess that cannot get metabolized will get converted to triglycerides and then stored.
When you are increasing the carbohydrate intake, you should be decreasing the amount of fat. If you're not, then at least you should be taking something that stimulates the oxidation of carbohydrate so that it doesn't result in the raising of triglycerides.
Aspirin, caffeine, especially vitamin B-3 niacinamide, all of these are known to lower triglycerides and, by now, the consensus mechanism of action is that all three of these components are increasing the oxidation of carbohydrates.
So, if you're increasing carbohydrates and you're getting an increase in triglycerides, two things, either you're eating too much fat or your baseline metabolic rate is not where it should be, so you can use some metabolic stimulation from these substances."
In addition to increasing the oxidation of glucose as fuel, aspirin, caffeine, and niacinamide may also inhibit the oxidation of fatty acids, specifically linoleic acid, and the most foundational strategy that anyone could implement to improve their health is to lower their linoleic acid, the omega-6 intake, into the 2- to 5-gram-a-day range. These supplements will also lower inflammation, which in turn will lower your baseline cortisol.
The metabolite of aspirin, salicylic acid, also has an inhibitory effect on the enzyme 11-beta-hydroxysteroid dehydrogenase Type 1. This enzyme synthesizes active cortisol from the inactive precursor cortisone.
"So, aspirin will actually lower your synthesis of cortisol directly, not just by lowering inflammation, but also lowering the actual synthesis of cortisol," Dinkov explains.
Aspirin also has an anti-lipolytic effect, not as strong as niacinamide, but it's got these three different things that are basically helping to lower both the supply of fat to the cell and excessive oxidation of fats even at these tiny dosages."
Be mindful about the aspirin you use, though. Immediate-release aspirin made with cornstarch is the preferred version that is now hard to find. Extended-release aspirin is not recommended due to the additives they put in it. Your best option would be to use a salicylic acid or willow bark supplement.
A word on daily aspirin before you act on any of this. Taking aspirin every day is a medical decision rather than a supplement choice. The U.S. Preventive Services Task Force recommends against starting low-dose aspirin for the primary prevention of cardiovascular disease in adults 60 and older, and treats it as an individual decision for adults 40 to 59 who have a 10-year cardiovascular risk of 10% or greater.
Aspirin may raise the risk of gastrointestinal bleeding, intracranial bleeding, and hemorrhagic stroke — one pooled analysis found a 58% increase in major gastrointestinal bleeding. Talk to your healthcare provider about whether a daily aspirin regimen is appropriate for you, particularly if you take an anticoagulant, a steroid or another NSAID.
Benefits of Vitamin E
Dinkov also reviews the benefits of other supplements, such as vitamin E, which inhibits lipolysis, improves glucose metabolism, acts as an estrogen antagonist and helps counteract much of the damage caused by linoleic acid and other polyunsaturated fats (PUFAs).
According to Dinkov, your need for vitamin E tracks your PUFA intake, at roughly 2 milligrams of vitamin E from all sources per gram of PUFA consumed.
Importantly, PUFAs aren't just the omega-6s. It's also omega-3. In the interview, Dinkov goes into detail as to why omega-3 supplements such as fish oil are not recommended.
Whole food, in this case, small fatty fish and wild-caught Alaskan salmon are really your best bet. It's virtually impossible to find fish oil that's not rancid. So, to review, when you're calculating your PUFA intake you also need to include your omega-3s. Ideally, your daily total PUFA intake would be below 10 grams, with linoleic acid — the omega-6 component — in the 2- to 5-gram range. That range has a floor as well as a ceiling: linoleic acid is essential and is required for mitochondrial function, so the goal is a return to the historical intake of 2 to 3 grams a day, not a drive toward zero.
How to Apply This When Using Time-Restricted Eating (TRE)
If you're using time-restricted eating, or considering starting, then this final side note will be important. If you're metabolically inflexible, insulin resistant, and unable to easily switch between burning sugar and fat as your primary fuel, then a period of time-restricted eating may be useful, whether you're eating a ketogenic diet or not. Current guidance treats this as a short-term measure for obesity and insulin resistance rather than a long-term practice — once metabolic flexibility returns, the restriction is meant to be relaxed.
However, once you regain your metabolic flexibility, which can take anywhere from a few weeks to a few months, you will need to increase your eating window. The reason for this goes back to the glucose-cortisol connection. Dinkov explains in this interview. Your body needs glucose, and if you deprive it for too long, it will produce cortisol to stimulate your liver to make it.
This increased cortisol can contribute to chronic inflammation and cellular damage. Therefore, once you are no longer insulin resistant, Dinkov's suggestion in this interview was an eating window of roughly eight to 12 hours, meaning you eat all of your meals for the day within this window, and fast for the remaining 12 to 16 hours. It is also best to avoid eating before sunrise or after sunset and at least three hours before bedtime.
More Information
To learn more, be sure to listen to the entire interview, as we dive into far greater detail than what I've summarized here. Georgi is an absolute fire hydrant when it comes to biochemical details.
Also check out Georgi's blog at www.haidut.me or follow him on Twitter. You can also obtain a major sampling of Ray Peat's work for free by going to these two sites: wiki.chadnet.org/Ray-Peat and RayPeat.com.
This article is for informational purposes only and does not constitute medical advice. Consult a qualified healthcare provider before making changes to your health regimen.