Ketosis: Fear, Uncertainty and Doubt

Perhaps nothing is more damaging to the new low-carber than the intentional spread of fear, uncertainty and doubt regarding the state of ketosis compared to the dangerous state of ketoacidosis. The former is a natural and healthy state of existence, the latter is a condition that threatens the life of type 1 diabetics and type 2 diabetics whose disease has progressed to the point where their pancreatic beta cells can no longer produce insulin (ketoacidosis is also a risk for alcoholics). So if you’re not an alcoholic, a type 1 diabetic or a late-stage type 2 diabetic, fear of ketosis is misdirected.  You should regard with suspicion anyone who confuses the two and warns you against a low-carb diet because they cannot tell the difference.

The confusion between ketosis and ketoacidosis is a sign of a grave misunderstanding of basic biology (if not a complete lack of critical faculty).  So too is the assumption that ketosis is the “early stage” of ketoacidosis or that “ketosis leads to ketoacidosis” in a person whose pancreas is still able to produce insulin.

If you don’t trust me (and why should you), you should consider listening to some people who know a lot more about this than either you or I ever will:

Nutritional ketosis is by definition a benign metabolic state…  by contrast, ‘diabetic ketoacidosis’ is an unstable and dangerous condition that occurs when there is inadequate pancreatic insulin response to regulate serum B-OHB. This occurs only in type-1 diabetics or in late stage type-2 diabetics with advanced pancreatic burnout. (Dr. Phinney & Dr. Volek, The Art and Science of Low Carbohydrate Living, p.4)

Later in the book (p.80), Phinney and Volek explain further:

[Type-1 diabetics] need insulin injections not just to control blood glucose levels, but also to regulate the release of fats from fat cells.  When fat cells release fatty acids too rapidly, ketone production becomes imbalanced, and this leads to diabetic ketoacidosis. Thus, ketoacidosis is is characteristic of type-1 diabetes, or of late stage type-2 diabetes that has progressed to the point that the pancreas can no longer produce the minimal amount of insulin required to limit fatty acid release from the body’s fat cells. (Dr. Phinney & Dr. Volek, The Art and Science of Low Carbohydrate Living, p.80)

The last point warrants repeating, because it is an important one.  Insulin regulates not just blood glucose, but also the production of ketone bodies.  When a person has an illness that inhibits their ability to produce insulin, they are at risk of ketoacidosis.  This excludes the vast majority of people…even most type-2 diabetics. Remember, type-2 diabetes is characterized by insulin resistance, not an inability to produce insulin). Because type-2 diabetics tend to overproduce insulin (because their cells need higher and higher doses of insulin to achieve the same effect), they typically are not at risk of ketoacidosis, regardless of diet.  It is only when a type-2 diabetic experiences pancreatic beta cell death (and the resultant inability to produce insulin), that they are at risk of experiencing ketoacidosis.

What then are ketones and ketosis?  Well, Ottoboni & Ottoboni provide an admirable overview:

Ketone bodies are fuel molecules that can be used for energy by all organs of the body except the liver. The production of ketone bodies is a normal, natural, and important biochemical pathway in animal biochemistry (7, p. 577). Small quantities of ketone bodies are always present in the blood, especially after several hours with no food.  But during fasting or carbohydrate deprivation, larger amounts of ketone bodies are produced to provide the energy for brain, heart, kidneys, and muscles normally provided by glucose.

The nutrition community has fostered the popular misconception that ketone-body production, per se, is an undesirable metabolic problem. It has labeled the formation of ketone bodies a dangerous consequence of low-carbohydrate diets in an effort to discredit any recommendations that deviate from the unified Dietary Guidelines (8). As a result, the public has come to view ketone bodies as a symptom of a pathological condition rather than a normal attempt by the body to satisfy its demands for energy when glucose supplies are short. (Ottoboni and Ottoboni, The Modern Nutritional Diseases, p.114)

Sound familiar?  If so, it’s because it’s the basic science of our biology: ketosis is a natural and benign state of existence. It is the result of our body’s attempt to use fat cells as fuel when glucose is not available.  Remember, ketone bodies are always present in the blood, and most people even enter a state of ketosis overnight/while they sleep.

There is no danger in being in ketosis for extended periods of time.  Ketones are normal fuels of respiration and don’t pose any problems over the long haul.  In fact, some research has shown that ketones are a preferred fuel of many organs including the heart. (Dr. Michael Eades, Low Carb Gaining a Foothold…)

And so it continues, on an on.  I’ve collected a series of quotes from trustworthy sources that can help you understand ketosis, and learn the differences between ketosis and ketoacidosis, so that you’ll understand just how big an idiot the next person is when they tell you, “ketosis is dangerous”.  It’s not. What is dangerous, however, is lack of knowledge and misrepresentation of basic human biology.

Dr. Michael Eades:

As the level of ketone bodies rises in the blood, it stimulates the release of insulin from the pancreas. The spurt of insulin then shuts down the process that makes ketones. Ketones only rise to dangerous levels in people who have type I diabetes and can’t make their own insulin. If the system didn’t work this way, people who starved would die from ketoacidosis relatively quickly, but they don’t; they live for weeks without food before they succumb to protein malnutrition, not ketoacidosis. (Dr. Michael Eades, Low Carb Diet Takes One Below The Belt)

Jeff Volek and Stephen Phinney:

One of the many myths about ketogenic diets is that they cause the body to go into a state of acidosis. This stems from the unfortunate fact that many doctors and lay people alike confuse nutritional ketosis (blood ketones at 1-3 millimolar) with keto-acidosis (blood ketones greater than 20 millimolar). In nutritional ketosis, blood pH at rest stays normal, plus sharp drops in pH due to CO2 and lactate buildup during exercise are restrained. By contrast, in keto-acidosis, blood pH is driven abnormally low by the 10-fold greater buildup of ketones. Suggesting these two states are similar is like equating a gentle rain with a flood because they both involve water. (Jeff Volek, PhD, RD & Stephen Phinney, MD, PhD, The Art and Science of Low Carbohydrate Performance)

Anssi H Manninen:

During very low carbohydrate intake, the regulated and controlled production of ketone bodies causes a harmless physiological state known as dietary ketosis. Ketone bodies flow from the liver to extra-hepatic tissues (e.g., brain) for use as a fuel; this spares glucose metabolism via a mechanism similar to the sparing of glucose by oxidation of fatty acids as an alternative fuel. In comparison with glucose, the ketone bodies are actually a very good respiratory fuel. Indeed, there is no clear requirement for dietary carbohydrates for human adults. (Anssi H Manninen, Metabolic Effects of the Very-Low-Carbohydrate Diets: Misunderstood “Villains” of Human Metabolism, Journal of the International Society of Sports Nutrition.)

Anssi H Manninen:

Diabetic patients know that the detection in their urine of the ketone bodies is a danger signal that their diabetes is poorly controlled. Indeed, in severely uncontrolled diabetes, if the ketone bodies are produced in massive supranormal quantities, they are associated with ketoacidosis [5]. In this life-threatening complication of diabetes mellitus, the acids 3-hydroxybutyric acid and acetoacetic acid are produced rapidly, causing high concentrations of protons, which overwhelm the body’s acid-base buffering system. However, during very low carbohydrate intake, the regulated and controlled production of ketone bodies causes a harmless physiological state known as dietary ketosis. In ketosis, the blood pH remains buffered within normal limits [5]. Ketone bodies have effects on insulin and glucagon secretions that potentially contribute to the control of the rate of their own formation because of antilipolytic and lipolytic hormones, respectively [9]. Ketones also have a direct inhibitory effect on lipolysis in adipose tissue [10]. (Anssi H Manninen, Metabolic Effects of the Very-Low-Carbohydrate Diets: Misunderstood “Villains” of Human Metabolism, Journal of the International Society of Sports Nutrition.)

Ansi H Manninen:

[…] A very-low-carbohydrate diet cannot lead to dangerous ketoacidosis in healthy individuals (without alcohol or drug abuse) because ketone bodies have effects on insulin and glucagon secretions that contribute to the control of their own formation. (Ansi H. Manninen, Life-threatening complications of the Atkins diet?, The Lancet)

Cahill & Veech:

It should be emphasized again that the level of insulin appears to be in control by its regulation of amino acid release from muscle. In the super-fasted state (the diabetic) where even basal insulin levels are inadequate, excessive amino acids are released from muscle, hepatic gluconeogenesis and ketogenesis increase and levels of glucose and ketones rise. These result in progressive hyperglycemia, hyperketosis and glucosuria and ketonuria (4). This is the syndrome of diabetic ketoacidosis, with acidosis, severe hypovolemia, hypotension and death unless interrupted by exogenous salt-containing fluids to correct volume and insulin to correct the underlying dys-metabolism. Simple starvation and/or the ketogenic diet produce a mild but closely regulated metabolic acidosis, compatible with normal life as evidenced by Inuit sur- vival before polluted by our American culture! (Cahill & Veech, Ketoacids? Good medicine?, Transactions of the American Clinical and Climatological Association)

Comstock & Garber:

In normal individuals plasma ketone levels are self-limited, because at 2 to 4 mM concentrations and greater, insulin release is stimulated, thereby preventing ketoacidosis by an insulin limitation of lipolysis and the availability of free fatty acids for hepatic oxidation. In the insulin-dependent diabetic, concentrations of free fatty acids continue to increase uncontrollably until ketoacidosis ensues. (Comstock & Garber, Clinical Methods: The History, Physical, and Laboratory Examinations, Chapter 140: Ketonuria)

Dr. Richard Bernstein:

[Diabetic ketoacidosis] occurs  in people who make virtually no insulin on their own (either type 1 diabetics or type 2 diabetics who have lost nearly all beta cell activity). Very low serum insulin levels, combined with the insulin resistance caused by high blood sugars and dehydration, result in the virtual absence of insulin-mediated glucose to the tissues of the body. In the absence of adequate insulin, the body metabolizes stored fats to produce the energy that tissues require to remain alive. a by-product of fat metabolism is the production of substances called ketones and ketoacids. (Dr. Richard Bernstein, Diabetes Solution, p.366)

Dr. Richard Bernstein:

Your physician should only fear ketoacidosis if [your urine] shows “high” ketones combined with high blood sugars (180mg/dl or above). (Dr. Richard Bernstein, Diabetes Solution, p.373)

Dr. Richard Bernstein:

In periods of famine, ketones enable humans to survive because the brain can use them as an energy source. Even without famine, many nonobese people will show positive tests for urinary ketones (ketonuria) after going without food all night.

Although we are taught in medical school that ketones are necessary for survival, physicians in training are subsequently traumatized by the sight of small children with very high blood sugars who are dying of dehydration, accompanied by high serum ketones. Thereafter they warn patients inappropriately that ketonuria with normal blood sugars is somehow hazardous. (Dr. Richard Bernstein, Diabetes Solution, p.204)

Lyle McDonald:

Despite oft-heard claims to the contrary, there is no actual physiological requirement for dietary carbohydrate. Even the RDA handbook acknowledges this, right before recommending that a prudent diet should contain a lot of carbohydrates. (Lyle McDonald, How Many Carbohydrates Do You Need?)

Lyle McDonald:

Since I’m going to use the term in just a second, I need to define what it means. When fatty acid burning is ramped up to high levels (as when carbohydrates are restricted), the body starts producing ketone bodies in the liver. As noted above, many tissues in the body can use ketones for fuel, basically they are an alternative energy source to glucose when it’s not available. When ketones build up in the bloodstream beyond a certain point, a condition called ketosis is said to develop. In contrast to the diabetic ketoacidosis (which occurs in poorly treated Type I diabetics), dietary ketosis is not dangerous and is an adaptation by the body to total starvation. (Lyle McDonald, How Many Carbohydrates Do You Need?)

Lyle McDonald:

Ketosis is defined clinically as a ketone concentration above 0.2 mmol/dl (6). Mild ketosis, around 2 mmol, also occurs following aerobic exercise. (4). The impact of exercise on ketosis is discussed in chapter 21.

Ketoacidosis is defined as any ketone concentration above 7 mmol/dl. Diabetic and alcoholic ketoacidosis result in ketone concentrations up to 25 mmol (6). This level of ketosis will never occur in non-diabetic or alcoholic individuals (12). (Lyle McDonald, The Ketogenic Diet)

Dr. Peter Attia:

Keto-adaption is a state, achieved through significant reduction of carbohydrate intake (typically to less than 50 grams per day), where the body changes from relying on glycogen as its main source of energy to relying on fat.  Specifically, the brain shifts from being primarily dependent on glucose, to being primarily dependent on beta-hydroxybutyrate.  This has nothing to do with what a diabetic patient is experiencing in DKA, but does illustrate how poorly informed and quick to react the medical community is.   DKA [Diabetic Ketoacidosis] and nutritional ketosis (or keto-adaptation) have as much in common as a house fire and a fireplace. (Dr. Peter Attia, Is Ketosis Dangerous)

Dr. Peter Attia:

A person with a normal pancreas, regardless of how long they fast (including the fellow I reference above who fasted for 382 days!) or how much they restrict carbohydrates, can not enter DKA because even a trace amount of insulin will keep B-OHB levels below about 7 or 8 mM, well below the threshold to develop the pathologic acid-base abnormalities associated with DKA. Let me reiterate, it is physiologically impossible to induce DKA in anyone that does not have T1D or very, very, very late-stage T2D with pancreatic “burnout.” (Dr. Peter Attia, Ketosis – advantaged or misunderstood state? (Part I))

Dr. Richard Atkins:

Ketosis is one of life’s charmed gifts. It’s as delightful as sex and sunshine, and it has fewer drawbacks than either of them. (Dr. Robert Atkins, Dr. Atkins New Diet Revolution 2nd. ed, p.58) (link leads to most recent edition)

7 Responses to “Ketosis: Fear, Uncertainty and Doubt”

  1. Thank you for explaining the “mmol/l math” of the range of levels (zero>traces>ketosis>DKA), plus the role of traces of insulin to naturally inhibit DKA levels occuring. This gives my T2DM friend confidence in tracking his progress using ketone blood sampling to confirm keto-adaptation is ocurring as planned so he can accustom himself to the state of ketosis and alter his carb intake to first define his own carb gram threshold and then shed fat in a controlled and predictable “formula”. Your “bias” is justified… we need this level of detailed explanation to truly understand the metabolic process so we both feel confident. I am familiar with LCHF just for shedding weight (16kg last summer), so helping my T2DM friend is a step up from my experience, that is more important to monitor.

    Reply
  2. Francisca

    Thank you so much!!!! I have just started a ketogenic diet and was in a panic after checking my urine keytone levels of 4mmol/l as a naturopath friend of mine scared me into thinking I was in danger!! Things are so much clearer now, I can’t thank you enough! 🙂

    Reply
  3. Thanks you! I am just embarking on this journey and even my doctor told me whom I asked for a referral to a nutritionist that there is a high likelihood that I will know more than the nutritionist! I am using summaries like yours and books of course to self educate. What a sad state we are in. And I am sure it has a LOT to do with financial interest from all over the place: sugar and grain producers, big pharma, even doctors who get paid for prescribing meds. It is ridiculous! Thank you for helping people who want to be healthy!

    Angela

    Reply
  4. Catherine

    I appreciate the clarifications about the safety of being in ketosis. It is by far the only approach that manages my cravings and gives me some peace. However, on two occasions in being in a ketogenic state, I have lost my hair. I am in the process of doing this again and it mystifies me. I am otherwise in good health and wondering what it is about the low carb high fat moderate protein approach would attach my hair. Any wisdom from these wise scientists would be so welcomed. Or a reliable support resource in Toronto that I may go to for guidance??

    Reply
    • Hi Catherine!

      Your hair loss is interesting. I’ve experienced it myself. It’s also often reported by bariatric surgery patients, and discussed occasionally by low carb dieters. It may be what’s called telogen effluvium, or hair loss resulting from interrupted hair growth patters. The causal factor: change in diet, dramatic weight loss, stress, etc…

      Some also speculate that decrease in certain vitamins may be to blame here. Others say that an excess in other vitamins is the cause. Certainly there are enough competing explanations to leave us all confused!

      And sadly, there isn’t the definitive research to point to (at least I haven’t found it).

      Where does that leave me?

      Well, my thinking is pretty much aligned with Dr. Eenfeldts on this: It’s usually nothing to worry about. (See his post on low carb and hair loss for details). BUT (and take note of the caps), I also advocate that you find a physician that understands low carb nutrition and is familiar with your medical history. There are some rather nasty pathologies that also result in hair loss, and it’s important that we all have a doctor who knows us and can keep an eye out for anything that looks suspicious.

      -Michael

      PS: From your post I wasn’t sure how to interpret the extent of your hair loss. Is it a general thinning like I experienced, or complete and total loss of all hair? Something in between?

      Reply
  5. Jera Jnin

    The one possible misconeception that also circulates in the diet industry is that ketosis is actually starvation. A certain plant based “doctor” aka diet guru likes to challenge the low carb meat eating community by saying a state of ketosis is the body starved from its preferred fuel, glucose. He also has multiple blogs and public attack on Dr. Atkins, making such bold claims that ketosis causes the body a state of illness much as during chemotherapy. i’m a big fan of Dr. A and it’s clear so many used his death as a pot shot against low carb. Do you have a more accurate account about ketosis however regarding the claims about starvation?

    Reply

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