A common question people have when starting keto is “will this kick me out of ketosis?” I’m going to address as many items as I can think of and explain why it will or will not kick you out of keto. This is going to be as comprehensive as possible so either use ctrl + f to find what you’re looking for or buckle up and read on.

How do humans enter ketosis in the first place?

Things will become much more clear if we explain how humans enter ketosis. Mainly, liver glycogen is what determines if ketones will be produced. Specifically, glycogen in the liver signals malonyl-coa to be formed by carboxylating acetyl-coa. Acetyl-coa is used in many processes and it’s the main substrate used to be turned into ketones.

The wiki on regulation of ketogenesis which applies to this scenario says “When the body has no free carbohydrates available, fat must be broken down into acetyl-CoA in order to get energy. Acetyl-CoA is not being recycled through the citric acid cycle because the citric acid cycle intermediates (mainly oxaloacetate) have been depleted to feed the gluconeogenesis pathway, and the resulting accumulation of acetyl-CoA activates ketogenesis.”

Basically, when there is more acetyl-CoA than oxaloacetate, the acetyl-CoA becomes acetoacetate, a ketone body. In plain English, carbs provide oxaloacetate, so if it doesn’t have carbs, it likely isn’t going to kick you out of ketosis. I’ll state the exceptions later.

Why do humans enter ketosis so readily?

Humans enter ketosis faster than any animal on the planet. It usually takes 24-36 hours before we enter ketosis.This is because we have huge brains and tiny bodies. Our brains need ~400 calories/day, which for most people that equates to 20% of our total energy demands. To put this in perspective, most animals only use 2-8% of their basal metabolism for their brain. This means our small liver glycogen stores of 100g are the only way of the brain getting glucose. There are no other glucose storage components that the brain can take from. This means at 400 calories/day, those 100g of glucose get used up in 24 hours. Doing the math, that means our brain consumes ~4g glucose/hour.

Therefore, even if something does kick you out of ketosis and we assume that all the glucose provided goes to the brain (it doesn’t), then just assume a 4g/hr clearance. Ate 20g extra carbohydrate? Don’t freak out, you’ll be back in ketosis within 5 hours max.

Where is the brain getting its energy?

Expanding on the above concept, if the brain doesn’t have glucose, the body will make ketones to feed it. The brain needs to get energy from somewhere, if not glucose, then where? Lactate can be used, but you need to be metabolizing carbs to get lactate, so that isn’t practical. Ketones are the only other solution. I ask this question often when people think something kicks them out of ketosis: “if not glucose or ketones, where is the brain getting its energy?” That question is the basic litmus test for ketosis. If the brain is short on energy by even just 50 calories, that will be made up by producing ketones. No energy for the brain = death. No exceptions. To find out if a biochemical scenario would kick you out of keto, ask “are they alive, then where is the brain getting energy?” Usually it’s glucose or ketones.

Does an insulin spike kick you out of ketosis?

Short answer: a little bit, but not really enough to freak out over because insulin clearance is fast.

Long answer: Here is a study where a dude fasted for almost a month. His ketones were high (14 mmol/l) and he was injected with insulin (around 0.1 IU/kg, so around 7-8 IU). For 30 min, his ketones and blood sugar dropped, there was a massive uptake of ketones by the brain and ketone production was halted. However, because insulin clearance is fast, within 30 min his ketones started shooting back up. It didn’t take him long even with insulin because no oxaloacetate was provided.

Fructose doesn’t spike my blood sugar, does that mean I won’t be kicked out of ketosis?

Fructose is the most anti-ketogenic sugar available. It cannot be metabolized anywhere but the liver because nothing else has the enzymes to metabolize it, therefore it refills liver glycogen rapidly. It is guaranteed to take you out of ketosis, alongside being harmful to the liver. Avoid it like the plague.

This means avoiding fruits also. It is better to consume 10g of fructose free carbohydrate (potato, rice, dextrose only candy like Smarties) than it is to consume 10g of fruit. On average, 50% of the carbs in fruit are fructose. Glucose can go to muscles instead of the liver, meaning liver glycogen stays empty. Fructose must be metabolized in the liver, meaning bye bye ketones.

What about gluconeogenesis (GNG)?

Okay this one is trickier. GNG happens all the time on keto. They are synonymous. In the scope of this article, we won’t address how “excess protein” impacts keto because that’s an article on its own. But lets talk GNG specifically.

GNG and ketogenesis can happen together. Just because GNG is initiated doesn’t mean ketosis stops. They occur together all the time. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2129159/ This study says “The hormonal changes associated with a low carbohydrate diet include a reduction in the circulating levels of insulin along with increased levels of glucagon. This activates phosphoenolpyruvate carboxykinase, fructose 1,6-biphosphatase, and glucose 6-phosphatase and also inhibits pyruvate kinase, 6-phosphofructo-1-kinase, and glucokinase. These changes indeed favor gluconeogenesis. However, the body limits glucose utilization to reduce the need for gluconeogenesis.”

The body doesn’t use as much glucose when glucose isn’t available (what a smart body), so therefore it doesn’t need GNG as much. In fact, there is little difference in the amount of glucose created via GNG on keto vs the amount created on a high carb diet.

That is enough evidence to show that ketosis and GNG happen together, but what of the glucose created via GNG?

Well, it doesn’t matter if the glucose provided via GNG becomes metabolized and produces oxaloacetate because GNG clears oxaloacetate. In essence, this means that regardless of glucose produced or metabolized via GNG, the oxaloacetate provided is likely to be retaken up as necessary to be used for GNG instead of beta oxidation of acetyl-CoA, meaning that acetyl-CoA can become a ketone. Yay!

Even if I consume all my protein at one meal vs 6?

Yes, regardless of the huge spike in insulin, as I stated above insulin itself will not destroy ketosis unless oxaloacetate is provided. Protein also spikes glucagon the same amount that it spikes insulin. Glucagon increases ketogenesis. No issues here.

When does fat become anti-ketogenic?

Fat is primarily ketogenic (90%) but also has a slight anti-ketogenic effect (10%). This represents the fact that ten percent of the total fat grams ingested will appear in the bloodstream as glucose (via conversion of the glycerol portion of triglycerides). If 180 grams of fat are oxidized (burned) per day, this will provide 18 grams of glucose from the conversion of glycerol.

What about artificial sweeteners?

Some artifical sweeteners do turn into glucose when metabolized. Look at this table and find your sweetener on it that you are about to consume. GI doesn’t always work as a direct comparison to glucose, since fructose doesn’t raise blood sugar but it does take you out of ketosis. So use this table, if the sweetener has a GI above 5, count it gram for gram as equivalent to any other carb. This means you can still consume it if you will stay under your carb limit for the day. For those sweeteners with a GI less than 5, count every 3g of the sweetener as 1g carbohydrate.

Alcohol?

Alcohol (ethanol) is metabolized into acetyl-CoA. It doesn’t provide glucose or oxaloacetate. If you don’t consume carbs with your alcohol, the alcohol actually increases ketosis because the acetyl-CoA:oxaloacetate ratio gets even higher. The body tries to clear the acetyl-CoA by producing more ketones.

The downside is that by providing more acetyl-CoA, alcohol stops your body from using its own fat stores to create more acetyl-CoA, therefore slowing down fat loss. Calories count.

Nuts, dairy, any other whole food?

Look at the carb count. How many carbs does it provide, and is that going to put you over your carb limit for the day? There is nothing magical in these foods that will take you out of ketosis.

Caffeine will not take you out of ketosis nor does it spike insulin.

What about the filler in pills?

Some pills use pure table sugar for filler, others use talc or another benign powder. Even if it happens to be pure sugar, weigh your pill. It’s likely only .5g, therefore it’s no more than .5g of sugar. Add it to your carb count if you’re that pedantic.

MSG – Monosodium glutamate

MSG is one sodium molecule (monosodium) bound to a glutamate molecule. Glutamate is a non-essential glucogenic amino acid. It can be converted to glucose, but nobody consumes enough MSG for this effect to be significant. Most of the time you’ll consume milligrams worth of MSG. Obviously many grams of carbohydrate will be necessary to kick you out entirely.

This article will be updated as other relevant questions arise.