Definitions of low-carbohydrate and ketogenic diets.

By Eugene J. Fine and Richard D. Feinman

Preliminary reports of the  USDA Guidelines for Americans Committee (DGAC) included  a definition of  low-carbohydrate diets as those with less than 45 % energy from carbohydrate. https://www.dietaryguidelines.gov/sites/default/files/2019-09/DP-ObesityProtocol-09-19-19.pdf . Long opposed to low-carbohydrate diets, little is expected of the DGAC.  The definition constitutes a disingenuous effort of the committee to comply with requirements of the National Academies and Congressional committees that they get serious, while still insuring that low-carbohydrate is not given adequate attention. Nobody working in this field would recognize 45 % as low-carbohydrate. The statement did however spark an exchange in an email discussion group that we belong to. The question was raised as to whether recommendations should be based on percentages of intake or absolute values in grams and even whether it should be the same for everybody: does an NFL linebacker have the same response to carbohydrate as a biochemistry professor (even one in CrossFit or Slow Burn)? In distinction to the common statement that there are no definition of low-carbohydrate diets, workers in the field generally agree that it is more precisely defined than other diets, The criteria in Table 1, reproduced in several peer-reviewed publications, represent a good guide on carb restriction [1].  In the email discussion, we pointed out that the most common cut-off is 130 g/day which the American Diabetes Association (ADA) [2] considers the boundary for low-carb. It turns out that the number is actually biologically meaningful and derived from the classic work of George Cahill on ketosis. 

Blood glucose and ketosis.

The 130 g cut-off for low-carbohydrate diets goes back to the original understanding of the role of ketone bodies and control of blood glucose. The major reason for the need to maintain constant levels of glucose resides in brain utilization. No other organ is as important for blood supply. The classic work from the 1960’s was carried out by Oliver Owen & George Cahill [3,4]. They studied brain metabolism under the “usual” conditions — in this case, signifying our western dietary culture where the mean carbohydrate (starches and sugars) consumption per day runs in the range of 300-400 grams. Owen and Cahill hospitalized 6 morbidly obese men and sampled from their carotid arteries and jugular veins (Figure 1) to measure the difference in glucose entry into and egress from the brain, that is, how much glucose was consumed by the brain. The method is very intuitive, very simple and very elegant. (It was also invasive. It hasn’t been repeated and it’s questionable whether it would be approved by Institutional Review Boards these days). The authors determined that the brain uses 130 grams of glucose/day. They also determined ketone body utilization using measurements form the same blood vessels. Under usual (ie, high carbohydrate) conditions, ketone body utilization was negligible. 

What Owen and Cahill did next was equally remarkable. The morbidly obese patients (none less than 300 pounds) were placed on a total fast for six weeks. They were provided, of course, with water as well as trace vitamins and minerals, but no caloric food. The goal was to determine what happened to brain metabolism when no carbohydrate (or any other macronutrient) was available. What happened was 65-70% of brain metabolism switched to ketogenic metabolism, using beta-hydroxybutyrate as a substrate to substitute for the absent glucose [Figure 2].  

Ketosis protects protein during starvation

During starvation glucose becomes unavailable, — glycogen from the liver runsout in a few days at most. Glucose is supplied by gluconeogenesis from other metabolites and these come mostly from body protein — the threat in starvation is not about energy per se but rather the loss of lean body mass.  As starvation proceeds nitrogen is removed from amino acids from protein — and the carbon skeleton is used for gluconeogenesis.  Thus, ketone bodies as an alternative fuel for the brain are able to relieve the demand on body protein for glucose and are said to be “protein sparing.” Figure 3 shows how, as starvation proceeds, less and less nitrogen in the form of urea or ammonia is excreted in the urine. Some glucose from gluconeogenesis (about 40 grams per day) is still required for the brain Roughly half is derived from protein and the other half from conversion of the glycerol backbone of triacylglycerol catabolism.  And that’s what Owen and Cahill found. 

Recommendations and Definitions.

Brain size and brain glucose requirements do not vary greatly (compared to variations in body size). On that basis, 130 g per day seems like a good ball park  number for the brain’s requirement for glucose under “usual” (non-starvation conditions where ketone bodies can supply more than half of the need). Practically speaking, while any reduction in dietary glucose (from sugar or starch) to under 130 grams/day will lead to ketogenesis,until brain glucose supply drops below 50g/day, the level of ketone bodies will not reach what we consider significant ketosis (say, at least 0.5 mM).  Dietary intake between 100-130 grams/ day of carbohydrate may be described as slightly reduced intake; less than 100 g. per day is low- carbohydrate but without significant ketosis. Less than 50 grams per day is the threshold for more substantial and physiologically measurable ketosis. Serious ketosis (say 1 mM and above) usually requires intake <30 grams/day.

It is important, though, to emphasize that 130 g/day does not constitute an indication of our dietary needs for glucose which is, of course, zero. There is no requirement for dietary carbohydrate. You know this because glycogen stores are small and would supply only a couple of days of glucose. Even thin people can go weeks or even months without food. It was described in Nutrition in Crisis [5] how many dietitians have misunderstood this point and tend to recommend, as part of their traditional opposition to low-carbohydrate diets, that 130 g. of dietary glucose is a requiement. In fact, this was due to misinterpretation by the Institute of Medicine. The misunderstanding of dietitians might be forgiven since it follows the pronouncements by a respected and authoritative source. George Cahill told us that by the time he realized what had happened, it was too late to change things. In any case, the 45 % of calories level of carbohydrate is likely to be recommended in the 2020 dietary guidelines and will insure that low-carbohydrate diets are categorized in such a way that they do not show unusual effects. This will be taken to support the long-standing mantra that only calories count although the data show that in head-to-head comparisons do better than controls, usually low-fat diets, for however long they are compared. 

Ketogenic  diets

The current interest in ketogenic  diets derives from new appreciation of the inherent metabolic effects of ketone bodies beyond reduction in carbohydrate and improvements in the glucose-insulin axis.  One of the desirable effects of the diet that is different from the evolutionary benefit in starvation is in “protein sparing.” Jennifer Elliott pointed out to us that people with diabetes generally only show an increase in nitrogen excretion. Why is this? The deficit from gluconeogenesis is made up by increased dietary protein consumption. George Cahill used to say that the Atkins diet was a high calorie starvation diet. 

References

  1. Richard D. Feinman, Wendy K. Pogozelski, Arne Astrup, Richard K. Bernstein, Eugene J. Fine, Eric C. Westman, Anthony Accurso, Lynda Frassetto, Barbara A. Gower, Samy I. McFarlane, Jörgen Vesti Nielsen, Thure Krarup, Laura Saslow, Karl S. Roth, Mary C. Vernon, Jeff S. Volek, Gilbert B. Wilshire, Annika Dahlqvist, Ralf Sundberg, Ann Childers, Katharine Morrison, Anssi H. Manninen, Hussain M. Dashti, Richard J. Wood, Jay Wortman, Nicolai Worm, (2015) Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition 31 1-13
  2. American Diabetes Association (2013) Nutrition Recommendations and Interventions for Diabetes–2013 Diabetes Care.
  3. Owen, OE Morgan, AP, Kemp, HG, Sullivan, JM, Herrera, MG, Cahill, GF, Jr. (1967) Brain metabolism during fasting, J. Clin. Investig. 46, 1589–159
  4. Owen, OE (2005) Ketone Bodies as a Fuel for the Brain during Starvation. Biochem and Molecular Biol Education 33, 246–251.
  5. Feinman, RD. (2019) Nutrition in Crisis, Chelsea-Green Publishing, White River Junction, VT. https://amzn.to/2L4f8tM

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