Thursday, January 13, 2011

High protein and ketosis

Traditional ketogenic diets are both low in protein and carbohydrates. The main argument is that because almost 60% of the ingested amino acids are glucogenic, one must also restrict protein intake to achieve ketosis. According to VanItallie and Nufert (see Ketosis Essentials):

"This occurs because approximately 48 to 58% of the amino acids in most dietary proteins are glucogenic. For every 2 grams of protein consumed in a carbohydrate-free diet, somewhere between 1.0 and 1.2 grams are potentially convertible to glucose. Therefore, to obtain a degree of hyperketonemia (approximately 2–7 mM/L) believed to be therapeutically effective in certain important medical conditions such as epilepsy, patients must rigorously restrict protein as well as carbohydrate intake and, when possible, increase their level of physical activity. (my emphasis)"
This is why, for example, a typical ketogenic diet to treat epilepsy utilizes a ratio of 4:1 or 3:1 (Fat:Protein+Carbohydrates). 

So what happens when we eat a high fat/high protein diet? Let's look at Eskimos (1). On average, they consume approximately 280g of protein, 125g of fat and 54g of carbohydrate. This gives us a total of 2461 kcal of which 45.5% is protein, 45.71% is fat, and around 8.77% is carbohydrate. This is both high protein and high fat, and very low carbohydrate. Kind of my ideal diet. When researchers studied their metabolisms, they found that they are not in ketosis during their usual diet. Ketosis is developed during fasting, but to a much lesser degree than other human subjects. The authors concluded:
"Eskimos show a remarkable power to oxidize fats completely, as evidenced by the small amount of acetone bodies excreted in the urine in fasting." 
Further studies showed the same results. For instance, Steffanson and Andersen, both who lived eating 9 years an Eskimo diet, participated in a controlled study eating only meat for one year (2). Besides health improvements, a very mild ketosis was observed, similar to the Eskimo studies. But these studies are really old (late 20's-early 30's) and the degree of ketosis was measured by urinary ketones. It is known that ketonemia is a better indicator of the degree of ketosis than ketonuria (3, 4, 5). This is very important because measuring ketosis by ketonuria tend to show many false positives (throw away dose damn strips!). 

During popular weight loss ketogenic diets, ketonuria (6, 7) and ketonemia (8) are observed despite the high percentage of calories derived from dietary protein. Even with a low calorie high protein diet (PSMF) ketonemia appears (9).

If KB are excreted by urine, why does ketonuria not always correlate with the degree of ketosis? The answer lies in KB metabolism. During fasting, KB start to rise until a plateau is reached almost at 5 days. This occurs both because of a reduced skeletal muscle clearance and decreased production by a negative feedback loop (10). The effect on KB removal rate is equal on both diabetic and normal subjects, only differing on the production rate of KB (ketogenesis)*. Urinary excretion of KB is always < 10% of total turnover. So the level of KB in plasma is determined by the difference between ketogenesis and clearance by extra hepatic tissues, while ketonuria accounts only for a small part of the equation. Increasing the utilization of ketones by peripheral tissues reduces its excretion, so one active keto-adapted person can be in strong ketosis but show almost no urinary ketones.

Although the degree of ketosis is dependent on the amount of dietary fat, there are some tools for increasing it without decreasing protein intake and/or increasing fat intake. Exercise has shown to increase both ketogenesis and metabolic clearance rate (11), but the effect on the latter is abolished at high concentrations (12) and when basal ketone concentrations are high (5.7mM) (13). This is because skeletal muscle adapts to use FFA as energy and spares ketones for non-FFA-using tissues, like the brain. During a LCKD, exercise enhances ketogenesis and the degree of ketonemia, as RQ values during exercise in ketogenic conditions have shown to be as low as 0.7 (14) and even 0.66 (15). In fact, post-exercise ketosis is a well known phenomenon (16). 

The hormonal environment is another factor that influences ketogenesis and plays a direct role in the enhancing properties of exercise. Insulin is the classic anti-ketogenic hormone, while catecholamines are strong ketogenic activators (17, 18). Exercise increases the body energy needs and catecholamine secretion, while decreasing insulin and glucose levels (16). With some differences, this scenario is similar during fasting. Traditionally, studies on FK and energy metabolism during fasting have been done during starvation, but lately ADF and IF is being studied as a potential therapy to treat and prevent several diseases. For example, ADF increases bOHB levels after 22 days even while eating ad libitum and without  carbohydrate restriction (19). Moreover, KB begin to rise after an overnight fast in "normal" people**. This is because during short term fasting the expression of PDK4, LDL, UCP3 and CPTI is increased, showing a "glucose-sparing" mechanism and shifting towards a lipolytic metabolism (20). This changes arent reversed by a LCKD, which has similar effects on gene expression. IF/ADF would potentiate the effects of a LCKD on ketogenesis, lipid metabolism and glucose sparing.

Another aspect which influences the degree of ketosis is food. It is well known that coconut oil (and specifically MCTs) increases plasma KB (21, 22). Black tea has also shown some ketogenic properties (23). Adrenergic stimulation by dietary stimulants (such as coffee or green tea) could induce ketogenesis, specially during a fast, where adrenergic sensitivity is increased. Both adrenaline and noradrenaline have ketotic effects (24). Catechin-poylphenols in green tea, for example, have shown to inhibit catechol-O-methyl-transferase and caffeine to inhibit transcellular phosphodiesterases (25).


You can eat a high protein diet and still induce strong ketosis. A combination of a high fat/high protein diet, resistance exercise and fasting (as per my recommendations in my introduction post) induces a strong metabolic response of adaptation to a ketotic environment, without worrying on specific macros or restricting too much protein intake.

Addendum: That certain amino acids are glucogenic means that they can potentially be converted to glucose. In this case, when keto-adapted, glucose needs are reduced, so is GnG. This has been observed in studies in which a severe carbohydrate restriction only increases GnG slightly after a few days (26, 27). Increasing glucogenic precursors per se does not rise BG levels (28)***, which might affect ketosis. Hepatic glucose output is an extremely well regulated process which serves to mantain BG levels in an adequate range and prevent hypoglycemia.  As keto-adaptation occurs, glycogenolisis is reduced and GnG increased, in a controlled manner. GnG must not be avoided, its the natural and optimal way to control glycemia****.

*The reason why ketoacidosis is not developed under non-diabetic circumstances is because of insulin, which controls the rate of ketogenesis and lipolysis. 
** "Normal" as someone who eats SAD or a high carbohydrate diet.
*** This is why protein does not rise BG levels.
**** In TIIDM subjects, for example, this HGO control is dysregulated so hyperglycemia occurs.


  1. awesome post, pretty much sums my 'diet' !!! yay, glad i found your blog, got some reading to do at work today haha(hater of desk job here)

  2. @malpaz:

    Thank you! Hope you find useful information.

  3. Thanks very much for starting this blog on the benefits of keeping a ketogenic way of eating. I look forward to reading more.

    Would you consider changing the colors of the blog so that it is easier to read? The dark background and small, light colored printing is difficult to read and not at all restful for the eyes.

    All the best to you.

  4. @H: Thanks for the suggestion. I really like this template but will consider changing colors. Maybe a bigger font will help?

  5. Let's look at Eskimos (1). On average, they consume approximately 280g of protein, 125g of fat and 54g of carbohydrate. This gives us a total of 2461 kcal of which 45.5% is protein, 45.71% is fat, and around 8.77% is carbohydrate.

    The claims in this paper are totally implausible. Every other paper I have read suggests that Inuits typically consumed a very high fat diet with less than 20% of kilojoules from protein and only 2% carbohydrate. They were known to selectively eat the fattiest parts of mammals.

    Stefansson and Anderson ate an ad libidum diet containing 15-20% protein and 80-85% fat.

    McClellan WS, DuBois EF: Clinical calorimetry XLV: Prolonged meat diets with a study of kidney function and ketosis.
    J Biol Chem 1930, 87:651-68.

    McClellan WS, Rupp VR, Toscani V: Clinical calorimetry XLVI: prolonged meat diets with a study of the metabolism of nitrogen, calcium, and phosphorus.
    J Biol Chem 1930, 87:669-80.

    Domestic cats and polar bears - which are the purest mammalian carnivores typically obtain less than 20% of their calories from protein.

  6. This is why, for example, a typical ketogenic diet to treat epilepsy utilizes a ratio of 4:1 or 3:1 (Fat:Protein+Carbohydrates).

    The ratio refers to the percentage of calories as fat. A 3:1 diet has 75% of the calories in the form of fat. A 4:1 diet has 80% of the calories as fat.

  7. blogblog,

    I have seen the studies on an all-meat diet before. In fact, they mention the study on eskimos I reference in the introduction. Problems with studying eating patterns among non-industrial populations include the external influence of researchers. I dont know what your point is but what I wanted to say with this post is that I dont think is necessary to worry about eating more than 0.8-1g/kg protein to be in ketosis. Maybe if you are interested in CR/IGF-1 restriction...if not, ad libitum is the way to go.

    Re KD for epilepsy: According to the last recommendations, fat calories can go up even to 90%.

  8. In the Stefansson and Andersen trial Bellevue every individual piece of food eaten was analysed for fat, protein and carbohydrate. The fat:protein:carbohydrate ratio was 78:22:2 overall. The study you mention is obviously flawed. It is apparent that fat consumption was underestimated and protein overestimated. No one is going to be eating 4g/kg protein for an extended period.

    90% of calories as fat seems quite reasonable for young children who have high energy needs - polar bears get about 90% of the calories from fat. The main problem is the actual "foods" used. It could be done just as easily with fatty meat and be far more palatable and healthier.

  9. That kind of diet is really good for building muscles. Take the necessary vitamin for your health.

    Supplements Canada

  10. I know IF is intermittent fasting, but what is ADF?

    What do you think of a ketogenic diet in terms of helping an autoimmune peripheral neuropathy? (I figure it won't hurt, anyway, and might help.)

    1. ADF = Alternate day fasting. 36h fast-24h eat.

      A ketogenic diet would probably be beneficial.

  11. I finally hit 0.5mmol/L of blood ketones today. I usually try to keep my protein less than 125g, but I had read before this shouldn't matter so I only loosely follow that. Although I do find that calorie restriction helps. I do wonder how people get kept adapted without it. Because I spent a month eating low carb and didn't get very high in blood ketones, but when I restricted calories it suddenly worked. Although I had also increased my exercise so maybe this explains it? Also, do you have any thoughts on resistant starch?