Is there a Plan B against chronic disease? — Healthy skepticism.

With alternating directions of skepticism, here are six skeptical views about ketosis and chronic disease.

1. Some healthcare providers are skeptical of ketones

Nova Max Plus blood glucose and ketone meter.

T.B. Van Itallie writes in the abstract to the Nutrition Reviews October 2003 article Ketones: metabolism’s ugly duckling,

“Ketones were first discovered in the urine of diabetic patients in the mid-19th century; for almost 50 years thereafter, they were thought to be abnormal and undesirable by-products of incomplete fat oxidation. In the early 20th century, however, they were recognized as normal circulating metabolites produced by liver and readily utilized by extrahepatic tissues. In the 1920s, a drastic “hyperketogenic” diet was found remarkably effective for treatment of drug-resistant epilepsy in children. In 1967, circulating ketones were discovered to replace glucose as the brain’s major fuel during the marked hyperketonemia of prolonged fasting. Until then, the adult human brain was thought to be entirely dependent upon glucose. During the 1990s, diet-induced hyperketonemia was found therapeutically effective for treatment of several rare genetic disorders involving impaired neuronal utilization of glucose or its metabolic products. Finally, growing evidence suggests that mitochondrial dysfunction and reduced bioenergetic efficiency occur in brains of patients with Parkinson’s disease (PD) and Alzheimer’s disease (AD). Because ketones are efficiently used by mitochondria for ATP generation and may also help protect vulnerable neurons from free radical damage, hyperketogenic diets should be evaluated for ability to benefit patients with PD, AD, and certain other neurodegenerative disorders.”

Many healthcare providers are still concerned about moderate (e.g., 1.0 to 3.0 mmol/L) levels of ketones in the blood. Even some manufacturers of ketone monitors remain skeptical of moderate levels of ketones in the blood. For example, this year’s Nova Max Plus blood glucose monitoring system (that also measures ketones) comes with a printed user manual that warns:

“Your blood β-ketone [i.e., blood beta hydroxybutyrate] test result is displayed on the monitor.

If test result is higher than 8.0 mmol/L (Ket), the monitor displays ‘HI.” You may have high blood β-ketone level. Retest your blood β-ketone immediately using a new test strip. If your reading is still high, you should treat as prescribed by your healthcare professional and/or contact your healthcare professional immediately.

If test result is lower than 0.1 mmol/L (Ket), the monitor displays ‘LO.’ No action is required.

NOTE: The normal adult blood β-ketone range for person without diabetes is less than 0.6 mmol/L. Consult with your healthcare professional for the blood β-ketone range that is appropriate for you. If the blood β-ketone result is between 0.6–1.5 mmol/L and glucose is more than 250 mg/dL, this may indicate development of a medical concern. You need to contact with your heathcare [sic] professional for assistance. If the blood β-ketone result is more than 1.5 mmol/L and glucose is more than 250 mg/dL, contact with your heathcare [sic] professional immediately. This indicates a risk of developing DKA [i.e., Diabetic Ketoacidosis].”

Some healthcare professionals equate ketosis with a total avoidance of vegetables and they firmly believe there is no reason to want to have moderate levels of blood ketones:

“These kinds of diets have been around for at least 100 years prior to Atkins. They showed Americans that if you made yourself sick enough, and I do mean sick enough, by eating such a bizarre meal plan as an all meat, dairy, egg meal plan with no carbohydrates that you would lose weight because you became sick. Part of that manifestation of sickness is ketosis. You go into ketosis. You lose your appetite because of this illness, and I got to emphasize illness. It is not a blissful state of ketosis as the promoters say. Because of this illness, you can’t eat and you lose weight.”

2. Evolutionists are skeptical of blaming metabolism

Beagle examining “dog vomit” slime mold.

The species Fuligo septica, commonly called “scrambled egg” or “dog vomit” slime mold, is one of more than 500 species of slime mold. It is one of the plasmodial slime molds which, at one phase in their life cycle when food is abundant, look quite normal as single cell organisms each with a single nucleus and each propelling itself to get to potential mates and potential meals of bacteria, yeasts, or fungi. However when meals become scarce, the individual plasmodial slime mold cells swarm together and fuse into one big bag of shared cytoplasm containing thousands of cooperating nuclei. This aggregate of cytoplasm and nuclei can move faster and search for food more thoroughly than the single nucleus cell version of itself. When eventually that aggregate also runs low on food, the nuclei cooperate to disperse a portion of the aggregated nuclei as spores to start a new search for food.

Given that a relatively simple species like Fuligo septica has a metabolism capable of traversing a complex life cycle in order to follow the food to unknown locations, it seems unlikely that our own metabolism is unable to follow the food stored in fat cells by and for itself. Like slime mold cells using chemical signaling (e.g., cyclic adenoseine monophosphate) to coordinate their efforts to follow the food, we also use system wide chemical signaling (e.g., β-hydroxybutyrate (βOHB)) to coordinate our cells in their efforts to follow the food we have stored as fat. Although all species, humans as well as slime molds, have a metabolism that is capable of following the food, humans have the unfortunate capacity to disorient our metabolism.

3. Some healthcare providers are skeptical of long term ketosis

Universal warning symbol.

Although not entirely opposed to the thought of blood ketones, the majority of healthcare providers are skeptical about the safety of long term ketosis as a treatment against chronic disease. For example, Dr. Maria-Eugenia Frigolet, et al. compiled a dozen warnings about the possible side effects of long term ketosis in the Annals of Nutrition & Metabolism article Low-Carbohydrate Diets: A Matter of Love and Hate. Those warnings vary from the socially inconvenient (e.g., bad breath and hair loss) to the potentially deadly (e.g., nonalcoholic fatty liver disease and cardiovascular disease) with many ailments in between (e.g., dry mouth, constipation, gastrointestinal problems, weakened bones, micronutrient deficiencies, dyslipidemia, kidney stones, and psychological problems).

4. Systems analysts are skeptical of blindly assuming variables are independent

Carpet abrasion: the consequence of an episode of syncope due to a lack of sodium.

Until it hit me in the face, I personally was unaware of our assumption that nutrient requirements are independent (e.g., the recommended amount of dietary sodium is independent of the amount of carbohydrates we eat). In reality, the recommended amount of sodium does depend upon the amount of carbohydrates we eat. As everyone with diabetes knows, eating carbohydrates increases blood glucose. And as every insulin manufacturer knows, blood glucose can be decreased by an increase in insulin. Less known, a sustained low level of insulin (e.g., from a sustained low level of blood glucose due to a sustained avoidance of carbohydrates) causes ketosis and natriuresis (i.e., the process of sodium excretion in the urine).

Drs. Volek and Phinney, the authors of The Art and Science of Low Carbohydrate Living, recommend that ketogenic dieters eat three to five grams of sodium per day (ideally in a homemade bone broth) to counteract the loss of sodium due to natriuresis. Although I am now in my 31-st month of a ketogenic diet, I initially neglected to follow their sodium recommendation (which is about twice the maximum amount of sodium recommended by the U.S. Dietary Guidelines), and I paid for my neglect with strange muscle aches while running and also a drop in blood pressure that caused a face plant one morning. These symptoms went away when I added a daily bowl of salty soup to my diet. Most long term ketogenic dieters have similarly concluded that they need substantially more dietary sodium than the 2.3 gram limit recommended in the 2015–2020 version of the Dietary Guidelines for Americans.

For decades the nutrient requirement statistical model, as presented in the Dietary Reference Intakes report, was based upon the assumption that nutrient recommendations are independent of the consumption of all other nutrients. The 2015–2020 version of the Dietary Guidelines for Americans has moved slightly away from that assumption by introducing the concept of “eating patterns” consisting of “interacting food components.” According to the Dietary Guidelines for Americans, An eating pattern represents the totality of all foods and beverages consumed. All foods consumed as part of a healthy eating pattern fit together like a puzzle to meet nutritional needs without exceeding limits, such as those for saturated fats, added sugars, sodium, and total calories. All forms of foods, including fresh, canned, dried, and frozen, can be included in healthy eating patterns.”
In other words, the 2015–2020 version of the Dietary Guidelines for Americans recognizes that there may be dependencies between nutrient requirements and other nutrients eaten but those dependencies between “interacting food components” must stay within an independent set of limits for saturated fats, added sugars, sodium, and total calories. In contrast to this new view from the dietary guideline committees, virtually every ketogenic dieter knows from experience that the sodium limit (and perhaps also the saturated fat limit) is very much dependent upon carbohydrate intake.

5. Some healthcare providers are skeptical of dietary fat

Fat accounts for about 75% of the calories in an avocado, which is similar to the percentage of fat in a ketogenic diet.

Many studies have shown that a large serving of fat quickly reduces the body’s sensitivity to insulin, thereby interfering with the body’s ability to lower high levels of blood glucose. For example, the recent article Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance in The Journal of Clinical Investigation by Hernandez et al. documents a study in which fourteen lean and healthy individuals drank 1.18 grams of palm oil for each Kilogram of body weight (i.e., that is 6.2 tablespoons of palm oil for a 150 pound person), resulting in “decreased whole-body, hepatic, and adipose tissue insulin sensitivity by 25%, 15%, and 34%, respectively.

Insulin insensitivity (i.e., insulin resistance) and therefore high levels of blood glucose can cause

  • hardening of the arteries,
  • heart disease,
  • stroke,
  • kidney disease,
  • blindness,
  • increased infections, and
  • loss of toes, feet, or fingers caused by poor circulation and infections.

Given that many studies show a large serving of fat is bad for health, it is not surprising that many people believe that an even larger serving of fat would be even worse.

6. Systems analysts are skeptical of blindly assuming linearity

This figure 2 is from The Institute of Medicine’s Dietary Reference Intakes publication.

However, the reasoning behind the idea that eating more fat is necessarily worse for our health is based upon the assumption that our metabolism is somewhat linear. Studies clearly show that a large serving of fat quickly reduces our health by reducing our insulin sensitivity (e.g., the Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance article by Hernandez et al.). Although it may initially seem obvious that eating even more fat would reduce our health even more, in reality our metabolism is highly nonlinear and more dietary fat does not necessarily reduce our health. Specifically, if your diet replaces enough glucose with enough fat, your metabolism switches into a state of ketosis in which the cellular preference for fuel switches from glucose to fat. In ketosis, blood glucose remains relatively low and therefore the problem of reduced insulin sensitivity is much less of an issue because insulin is not needed to lower an already low level of blood glucose.

We would all be more aware and interested in our metabolism’s ability to switch into ketosis if we were born able to see exhaled carbon dioxide, perhaps as a greenish smoke. Then we would be able to see ketosis, as it causes a person’s Respiratory Quotient (RQ), the ratio of carbon dioxide produced to oxygen consumed, to decrease by as much as 30%. My personal interest in carbon dioxide exhaust started with a job. About 20 years ago I helped write software that slightly reduced the carbon dioxide produced by a coal fired steam generator. By polling an assortment of sensors, the software calculated the optimal time for steam generator tube cleaning, performed by a large rod called a “soot blower” that occasionally (e.g., about every 12 hours) moved around and sprayed water while the power plant was fired up and fully operating. Cleaning too frequently unnecessarily dampened the fire. Cleaning too infrequently allowed a buildup of insulating carbon on the steam generator tubes. In that energy industry project, even a 1% decrease in coal burned and the corresponding 1% decrease in carbon dioxide waste was very significant, which makes a 30% decrease in a body’s production of waste carbon dioxide seem spectacular to me, even though the comparison is not entirely consistent: the power plant’s carbon dioxide waste decrease is due to a process change (i.e., timing of cleaning) and the body’s decrease is due to a fuel change (i.e., fat instead of glucose).

If we could see our abrupt switch into ketosis simply by looking at our exhaled breath, we would quickly abandon our unrealistic mental model of our metabolism being linear. In addition to changing our perception of a high fat diet, accepting that our metabolism is a highly nonlinear system would also change our recommended dietary allowance (RDA) for nutrients because the current RDA recommendations are based upon the unrealistic assumption that our metabolism is linear. Specifically, figure 2 (above) shows the Normal nutrient requirement distribution and the cumulative 97.5% cutoff defined as the RDA. Because of our false assumption that metabolism is linear, the Normal nutrient requirement distribution (i.e., system input) maps into a Normal distribution of health outcomes (i.e., system output) and we incorrectly conclude that 97.5% of us will have good health outcomes by eating a diet that meets the RDAs.

The 20 year old nutrient requirement linear models defined in the Dietary Reference Intakes — The Essential Guide to Nutrient Requirements by the Institute of Medicine and used in every subsequent dietary guidelines publication will need to change in order to finally include the option of a healthy ketogenic eating pattern.

[end of installment 3]