How Vinegar Can Kick You Into And Out of Ketosis

It's all about the dose!

To my knowledge, there are no human studies showing that vinegar raises ketones, and this is supported by a 2018 review cited in a 2020 case report whose authors were also unaware of such studies.

However, animal studies support vinegar being ketogenic, and this is predicted from the most basic biochemistry of ketogenesis.

In “This is How Ketogenesis Works,” I covered how the central determinant of ketogenesis is the ratio of acetyl CoA to oxaloacetate.

Acetyl CoA consists of acetate bound to coenzyme A (CoA).

Carbs make both acetyl CoA and oxaloacetate, so they are not ketogenic. Fatty acids make acetyl CoA but not oxaloacetate, so they are ketogenic. In the presence of carbs, oxaloacetate gets made, so carbs suppress the ketogenic effect of fats.

Carbs can nearly abolish the ketogenic effect of long-chain fats. As I covered in How Insulin Stops Fat-Burning, carbs turn off the carnitine shuttle, which is required to import long-chain fatty acids into the mitochondria where they generate acetyl CoA. (For context, see also Why Insulin Doesn’t Make Us Fat).

MCT oil and to a much lesser extent coconut oil are independently ketogenic even in the presence of a high carb load, because fatty acids with 10 or fewer carbons efficiently enter the mitochondria without the carnitine shuttle, and therefore generate acetyl CoA without generating oxaloacetate.

Of course, you would generate more ketones from them if you restricted carbs, since you would have less oxaloacetate. And you would generate even more if you restricted protein, since many amino acids can generate oxaloacetate.

The acetic acid in vinegar is the acetate that binds to CoA to make acetyl CoA and it cannot generate oxaloacetate. Specifically, acetate easily slips through the mitochondrial membranes on its own and then acetyl CoA synthetase (also known as acetate CoA ligase) uses ATP to join acetate to CoA, forming acetyl CoA. Therefore, unless all the known biochemistry is fundamentally flawed, it is impossible for acetic acid not to be ketogenic even in the presence of carbs.

Indeed, doses of 50-200 milligrams of acetic acid are dose-dependently ketogenic in rats, and this is the equivalent of humans consuming 3-13 grams. This was true even in rats on a standard carb-inclusive stock diet, though feeding them a low-protein diet enhanced the ketogenic effect.

Nevertheless, too much acetic acid can kick you out of ketosis.

The difference between acetic acid and a long-chain fatty acid is that long-chain fatty acids are joined to CoA using ATP from the cytosol, whereas acetic acid is joined to CoA using ATP from the mitochondrion.

In 1988, Richard Veech, the student of Hans Krebs (of “Krebs Cycle” fame), and one of the fathers of metabolomics and advocate of the health benefits of ketones, performed an experiment to try to understand why high doses of sodium acetate used in dialysis buffer could cause adverse effects such as lower blood pressure and flushing.

Injection of 1.2 grams of sodium acetate into rats failed to elevate ketone bodies at all in this experiment. This is the equivalent of a human consuming 78 grams.

The primary metabolic harm of this massive dose of sodium acetate was excessive hydrolysis of mitochondrial ATP used to join acetate to CoA. This led to the buildup of pyrophosphate (two phosphates chopped off from the ATP molecule). This, in turn, diverted energy away from ATP synthesis and toward bringing in positively charged calcium to balance the negatively charged pyrophosphate (achieving electric neutrality so the mitochondrion doesn’t explode). This then led to precipitation of calcium with the pyrophosphate, damaging the mitochondrion and its ability to both burn glucose and generate ketones. 

The most dramatic change representing these metabolic abnormalities that can be easily measured at home was a 65% increase in plasma glucose and a failure to increase ketones.

These experiments suggest 3-13 grams of acetic acid can kick you into ketosis but that 78 grams will kick you out.

The area in the middle is a gray area that it makes sense to completely stay away from.

Braggs Apple Cider Vinegar is 5% acetic acid, so this is the equivalent of 4-17 tablespoons kicking you into ketosis and wildly higher amounts kicking you out, without knowing the starting place for the decline of the ketogenic effect.

Medical use of sodium acetate infusions have suggested that humans are capable of metabolizing 11.8-17.7 grams of acetate per hour before acetate levels would excessively accumulate. Elemental diets have in the past used as much as 12 grams of acetate per day in amino acid salts. The much higher amounts analogous to those used in the Veech experiment lower blood pressure and cause flushing, and in the rats elevate blood glucose.

There is probably some risk of acidosis when straight vinegar is combined with other factors. For example, this case report documented acidosis in someone on metformin and a ketogenic diet who regularly used vinegar. In this case, metformin is raising lactic acid by inhibiting complex I of the respiratory chain and the ketogenic diet is increasing ketones, which are acidic.

You can neutralize the acidity of apple cider vinegar with baking soda. Mixing 1/4 teaspoon of baking soda with 1 tbsp apple cider vinegar in a cup of water brings the pH to 6.5 and imparts a fizzy flavor, and using 1/2 teaspoon completely neutralizes the acidity.

This is because the bicarbonate reacts with the protons associated with the acetate to form water and CO2. The CO2 makes fizz, and then leaves as the drink turns flat. The H+ ions left to become water molecules and positively charged sodium was left over to balance the negative charge of the acetate. You thus now have fully dissolved (ionized) sodium acetate.

The principle signs you have too much vinegar in your system would be elevated blood glucose (shown in rats), acidic urine pH (below 6 would be the beginning of mild concern), breathing faster (a predictable physiological response to acidity), or, as documented in the case of massive boluses of sodium acetate used in dialysis, a drop in blood pressure or a flushing response.

Notably, a decline in the dose-dependent ketogenic effect or a mild elevation of blood glucose probably mark the transition between healthy or neutral “kicking you into” ketosis and the unhealthy “kicking you out of” ketosis.

If you’re on keto have you played around with vinegar? Let me know in the comments!