The mystery of the ketogenic diet: benevolent pseudo-diabetes

Mikhail Blagosklonny

Received 28 Jun 2019, Accepted 11 Jul 2019, Published online: 01 Aug 2019

https://doi.org/10.1080/15384101.2019.1644765

Abstract

Designed a century ago to treat epilepsy, the ketogenic diet (KD) is also effective against obesity and diabetes. Paradoxically, some studies in rodents have found that the KD seemingly causes diabetes, contradicting solid clinical data in humans. This paradox can be resolved by applying the concept of starvation pseudo-diabetes, which was discovered in starved animals almost two centuries ago and has also been observed in some rapamycin-treated rodents. Intriguingly, use of the KD and rapamycin is indicated for a similar spectrum of diseases, including Alzheimer’s disease and cancer. Even more intriguingly, benevolent (starvation) pseudo-diabetes may counteract type 2 diabetes or its complications.¹

Comment

In this fascinating paper, Mikhail Blagosklonny discusses the conflict between the overwhelmingly positive effects seen from low-carbohydrate and ketogenic diets in metabolic syndrome and diabetes and the apparent causing of metabolic syndrome by these diets in some animal studies.

The suggestion has also been made repeatedly in the media that insulin resistance is caused by ketogenic diets (mainly demonstrated in animal studies) and this can be demonstrated in oral glucose challenge tests after a ketogenic diet in both animal and human subjects.  

In the paper above, Blagoskonny discusses ‘starvation diabetes’, a condition observed in rabbits and dogs. This is observed to occur because with long-term starvation, despite ketones being produced, it is still desirable for the body to preserve glucose for use by the neurons of the brain and central nervous system and so, along with low insulin levels, insulin resistance goes up and this reduces the ability of tissue throughout the body (but not so many neurons that don’t require insulin for transporting glucose) to take up glucose, leaving it available for use by the brain. In other words, when there is both low overall fuel availability and low carbohydrate availability, the body will reduce the ability of tissue throughout the body to take up glucose, so as to preserve it for use by the brain and nervous system. This ‘starvation diabetes’ can also be elicited by very low carbohydrate ketogenic diets, especially if also calorie restricted.

When starvation diabetes-like effects are observed as a result of a nutrient-replete ketogenic diet, it has been called ‘benevolent pseudo-diabetes’ and is actually believed to be protective against the typically observed negative effects of diabetes like neuropathy and retinopathy (amongst others) and is also quickly reversed upon resumption of eating a normal diet that is higher in carbohydrate content. Thus, this type of insulin resistance is an adaptation that helps, rather than hinders, and is quite different to the long-term insulin resistance caused by a diet rich in sugar and carbohydrate from ultra-refined foods and other negative lifestyle factors.

The take-home messages from this paper, matched to my clinical observations are several.

1. Humans and rodents are quite different. The conclusions from rodent studies on keto and low carb provide for hypotheses that should be investigated in humans. They should never be applied to humans independently as rodents basically suck at ketosis compared to humans!
2. Transient insulin resistance as shown by an oral glucose tolerance challenge after being on a keto-diet doesn’t actually indicate insulin resistance present with metabolic syndrome, pre-diabetes and diabetes.
3. Transient ‘benevolent pseudodiabetes’ provides benefits to people when in a calorie and carbohydrate-restricted state.

References

1.            Blagosklonny MV. The mystery of the ketogenic diet: benevolent pseudo-diabetes. Cell Cycle. 2019:1-7.