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What is the Keto Diet (Ketogenic Diet Guide)

6th May 2022

You may have heard of the ketogenic diet or ‘keto’ before. This is a diet that is very low in carbohydrates. In contrast with a regular low carb diet (under 130g carbs per day), a ketogenic diet usually contains somewhere in the region of 20-50g carbs per day, depending on how ‘carbohydrate tolerant’ an individual is.

The carbs are kept very low so as to encourage the body to burn fat instead of glucose, as with a low carb diet. With a ketogenic diet however, the intake of carbs is low enough, and the rate of fat burning is high enough, to allow the body to greatly increase its production of ‘ketones’ – compounds that are formed from burning fat which themselves are energy sources. A ketogenic diet is eaten for the specific purpose of entering a state of ‘nutritional ketosis’, where blood ketone levels rise to 0.5 - 3.0 mmol/L.

So why do some people choose to keep themselves in ketosis? Some benefits come directly from cutting the carbs, as with a regular low carb diet, but there are also some benefits that are specifically attributable to ketones themselves, since they can change the expression of genes involved in processes such as inflammation and metabolism.

There’s a range of potential applications for a ketogenic diet, some of which are well-characterised and some of which are newly emerging and have yet to be studied extensively. Let’s take a look at some of them.

Weight loss

Perhaps the most obvious reason to take up a ketogenic diet would be weight loss. A standard low carb diet has been shown to be effective for weight loss, and some people may wish to lower their carbs even further, into a ketogenic range, to enhance their fat-burning capabilities even more.

High insulin levels decrease the body’s ability to burn fat in a number of ways [1-2], so lowering insulin levels by reducing carb intake logically increases fat-burning. A ketogenic diet in particular is able to prime the body to burn both dietary fat and stored body fat, thus providing a mechanism for weight loss. Ketogenic strategies are now being proven effective for weight loss in high-quality studies [3].

A four-week pilot study found that a ketogenic diet can effectively reduce body weight and fatty liver in morbidly obese patients scheduled for bariatric surgery, which makes the procedure less challenging [4]. One might wonder how these patients would’ve fared if simply left on the diet, rather than having a large part of their stomach cut out.

Control of blood glucose and insulin levels

Besides weight loss, there are plenty of other metabolic benefits associated with a ketogenic diet. As with a regular low carb diet, a ketogenic diet allows greater control of blood glucose and insulin levels, as dietary carbohydrates are a driving factor in these [5]. This is of particular interest to those with prediabetes, type 2 diabetes and even type 1 diabetes. While a regular low carb diet may be enough for some people to place their type 2 diabetes in remission, others may see more favourable results by dropping the carbs to a ketogenic level.

Interestingly, an SGLT-2 inhibitor drug known as empagliflozin, which is used for management of type 2 diabetes, has effects that mimic the principle effects of a low carb, ketogenic diet: decreased glucose burning and increased fat burning [6].

Epilepsy

Ketogenic diets were commonly and effectively used to treat epilepsy from the 1920s, however they fell somewhat out of favour after the development of anticonvulsant drugs. Research in the area has become somewhat intensive once again, but the ketogenic diet is usually used only on refractory (drug-resistant) epilepsy after drug treatments fail [7-8]. The diet seems to help through a number of mechanisms, including increased efficiency and production of mitochondria – the powerhouses of our cells.

Alzheimer’s disease

Recent literature suggests Alzheimer’s could be a primarily metabolic disease as it features a number of metabolic dysfunctions including similar mitochondrial dysfunctions to those seen in epilepsy [9]. Theoretically then, the ketogenic diet has potential to treat and prevent Alzheimer’s disease. As this is an emerging field of research, studies have been limited by small sample sizes, use of animal models or lack of a control group; however, the results so far are promising and may pave the way to more definitive findings [10-11].

Mental clarity

The brain benefits of a ketogenic diet aren’t necessarily restricted to those with epilepsy or Alzheimer’s disease. Increased use of ketones as an efficient energy source, along with the aforementioned improvements in mitochondrial function, can allow for better mental clarity in healthy individuals. However, most of the evidence for this is so far anecdotal.

Improved mood

It is thought that certain types of depression have a metabolic component. Therefore, a ketogenic diet which improves metabolic health, particularly in the brain, could improve depressive symptoms. Again, while there is plenty of anecdotal evidence for this, there is a lack of scientific literature thus far, with most studies being performed on rodents [12-13].

Endurance athleticism

It is often opined that carbohydrates are essential to exercise, particularly endurance exercise, where ‘carb loading’ is often practised to top the muscles up with glycogen (the body’s store of glucose). However, the body can only accommodate around 2000 kcal of glycogen (~1600 in the muscles and ~400 in the liver) [14]. On the other hand, even the leanest of individuals have tens of thousands of calories (kcal) stored in their body fat.

While people on a high carb diet rely on muscle glycogen and can struggle to access their fat stores efficiently, ‘keto-adapted’ athletes have an increased ability to burn fat for fuel, thus allowing them access to a much larger reservoir of energy [15]. In the context of endurance events, having a larger supply of energy is very much an advantage, and is perhaps why many endurance athletes are now employing a ketogenic approach.

Cancer

Ketogenic diets are also showing promise as an adjuvant cancer therapy that could render cancer cells more susceptible to radiotherapy and chemotherapy. It is thought that ketosis puts stress on cancer cells by restricting the glucose that they normally thrive on and selectively increasing reactive oxygen species (damaging molecules) in cancer cells [16].

In addition, beta-hydroxybutyrate, which is the main ketone body produced by the body on a ketogenic diet, has been shown to protect healthy cells from oxidative stress and inflammation – two processes that can promote the development of cancer [17-18].

A diet with potential

So as we can see, there are a range of potential benefits of ketogenic diets, some of which are amplified benefits of a low carb diet, coming directly from lowering the carbs, and others that may be specific to ketosis itself. Many of these benefits are just beginning to emerge in the scientific literature, and with interest in the field growing, it’s likely we’ll be seeing further developments on these in the future.

References

  1. Dallon, B.W., Parker, B.A., Hodson, A.E., Tippetts, T.S., Harrison, M.E., Appiah, M.M.A., Witt, J.E., Gibbs, J.L., Gray, H.M., Sant, T.M. and Bikman, B.T., 2017. Insulin selectively reduces mitochondrial uncoupling in brown adipose tissue in mice. Biochemical Journal, 475(3), pp.561-569.
  2. Strålfors, P. and Honnor, R.C., 1989. Insulin‐induced dephosphorylation of hormone‐sensitive lipase: Correlation with lipolysis and cAMP‐dependent protein kinase activity. European journal of biochemistry, 182(2), pp.379-385.
  3. Hallberg, S.J., McKenzie, A.L., Williams, P.T., Bhanpuri, N.H., Peters, A.L., Campbell, W.W., Hazbun, T.L., Volk, B.M., McCarter, J.P., Phinney, S.D. and Volek, J.S., 2018. Effectiveness and safety of a novel care model for the management of type 2 diabetes at 1 year: an open-label, non-randomized, controlled study. Diabetes Therapy, 9(2), pp.583-612.
  4. Schiavo, L., Pilone, V., Rossetti, G., Barbarisi, A., Cesaretti, M. and Iannelli, A., 2018. A 4-Week Preoperative Ketogenic Micronutrient-Enriched Diet Is Effective in Reducing Body Weight, Left Hepatic Lobe Volume, and Micronutrient Deficiencies in Patients Undergoing Bariatric Surgery: a Prospective Pilot Study. Obesity surgery, pp.1-10.
  5. Volek, J.S., Phinney, S.D., Forsythe, C.E., Quann, E.E., Wood, R.J., Puglisi, M.J., Kraemer, W.J., Bibus, D.M., Fernandez, M.L. and Feinman, R.D., 2009. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids, 44(4), pp.297-309.
  6. Ferrannini, E., Muscelli, E., Frascerra, S., Baldi, S., Mari, A., Heise, T., Broedl, U.C. and Woerle, H.J., 2014. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. The Journal of clinical investigation, 124(2), pp.499-508.
  7. Augustin, K., Khabbush, A., Williams, S., Eaton, S., Orford, M., Cross, J.H., Heales, S.J., Walker, M.C. and Williams, R.S., 2018. Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders. The Lancet Neurology, 17(1), pp.84-93.
  8. Nei, M., Ngo, L., Sirven, J.I. and Sperling, M.R., 2014. Ketogenic diet in adolescents and adults with epilepsy. Seizure, 23(6), pp.439-442.
  9. Demetrius, L.A. and Driver, J., 2013. Alzheimer’s as a metabolic disease. Biogerontology, 14(6), pp.641-649.
  10. Pinto, A., Bonucci, A., Maggi, E., Corsi, M. and Businaro, R., 2018. Anti-Oxidant and Anti-Inflammatory Activity of Ketogenic Diet: New Perspectives for Neuroprotection in Alzheimer’s Disease. Antioxidants, 7(5).
  11. Taylor, M.K., Sullivan, D.K., Mahnken, J.D., Burns, J.M. and Swerdlow, R.H., 2018. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 4, pp.28-36.
  12.  Sussman, D., Germann, J. and Henkelman, M., 2015. Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring. Brain and behavior, 5(2), e00300.
  13. Murphy, P., Likhodii, S., Nylen, K. and Burnham, W.M., 2004. The antidepressant properties of the ketogenic diet. Biological psychiatry, 56(12), pp.981-983.
  14. Wasserman, D.H., 2009. Four grams of glucose. American Journal of Physiology-Endocrinology and Metabolism, 296(1), pp.E11-E21.
  15. Volek, J.S., Freidenreich, D.J., Saenz, C., Kunces, L.J., Creighton, B.C., Bartley, J.M., Davitt, P.M., Munoz, C.X., Anderson, J.M., Maresh, C.M. and Lee, E.C., 2016. Metabolic characteristics of keto-adapted ultra-endurance runners. Metabolism, 65(3), pp.100-110.
  16. Allen, B.G., Bhatia, S.K., Anderson, C.M., Eichenberger-Gilmore, J.M., Sibenaller, Z.A., Mapuskar, K.A., Schoenfeld, J.D., Buatti, J.M., Spitz, D.R. and Fath, M.A., 2014. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism. Redox biology, 2, pp.963-970.
  17. Newman, J.C. and Verdin, E., 2014. β-hydroxybutyrate: much more than a metabolite. Diabetes research and clinical practice, 106(2), pp.173-181.
  18. Youm, Y.H., Nguyen, K.Y., Grant, R.W., Goldberg, E.L., Bodogai, M., Kim, D., D'agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T.D. and Kang, S., 2015. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nature medicine, 21(3), p.263.