Ketone Bodies for Optimal Health

screen-shot-2017-02-13-at-13-54-02

The ketogenic diet is a high-fat, low-carbohydrate diet that is frequently used in medicine to treat drug resistant epilepsy. This diet is becoming increasingly popular in the news due to its suggested ability to cause weight loss and improve brain function.

In this post Brianna Stubbs, DPhil student in metabolic biochemistry at Oxford University, explains exactly what ketosis is, how the ketogenic diet is used to treat disease, and benefits for the general population.

Discovery of ketone bodies

Ketone bodies were first discovered in humans when physicians in the late 19th century observed them in the urine of acutely ill diabetic patients. Since their discovery they have gone from a hallmark of disease to a central characteristic that has sustained human evolution due to the human body’s ability to produce and metabolise ketone bodies.

The human brain is very greedy in terms of energy, accounting for 20% of our daily total basal metabolic rate. However, the brain normally derives all of its energy from carbohydrates, as it is unable to burn fat. Fat stores contain a great deal more energy than carbohydrate stores, however this would be inaccessible to the brain were it not for ketone bodies. Ketones are produced from fat during fasting when carbohydrate stores are depleted. This allows the brain to make use of the energy contained in fat to continue to operate (1). Without this adaptation, our ancestors would have fallen unconscious and died as their carbohydrate stores ran out.

Insulin is a hormone released in response to dietary carbohydrate. If insulin stores are kept low for several days, fat is released from the cells where it is stored, travels to the liver and is converted to ketones. As blood ketone concentrations increase through fasting, the body enters a state of physiological ketosis (2). This state is maintained by feedback inhibition of ketone bodies on their own production. Pathological ketosis is seen in diabetics, where ketone production is dysregulated and can reach excessively high levels (3). A such concentrations the buffering capacity of the blood is exceeded and the resulting metabolic acidosis can be fatal.

However, physiological amounts of ketones have a role as a metabolic fuel and as a signal to regulate the mobilisation and utilisation of other fuels (4). Ketones slow down liver glucose production and decrease the rate of protein breakdown in the body, which protects against muscle wastage during periods of starvation.

Nutritional strategies to create ketosis without fasting are now being developed. This include ketogenic diets that stimulate ketone production through increased fat consumption whilst strictly limiting carbohydrate intake. There is a growing body of evidence to support the utility of nutritional ketosis for optimising health and also exercise performance (5).

The Ketogenic Diet and Health

Nutritional ketosis has several applications that are already documented in medicine. A ketogenic diet has been the only effective treatment for drug resistance epilepsy, in some cases completely eliminating seizures (6).

Ketogenic diets have also been shown to be a highly effective strategy for weight loss compared to calories restricted, non-ketogenic diets. This is in part due to the appetite suppressing effect of the diet, making it easier to consume fewer calories (7). During ketosis, ketone production from fat occurs at a steady rate throughout the day and so it is reported that energy levels and ‘fulness’ are more stable when the body is using ketones as a fuel compared to the oscillations experienced as a consequence of the repeated fluctuations in blood sugar that accompany carbohydrate rich meals and snacks.

A ketogenic diet may also benefit patients suffering with diseases that are characterised by harmful alterations in metabolism such as type two diabetes, Alzheimer’s Disease and even cancer.

For type two diabetes, a low carbohydrate, ketogenic diet can decrease levels of insulin and reduce fluctuations in blood glucose (8).

Symptoms of Alzheimer’s Diseases have improved in some reported cases following consumption of medium chain triglycerides (MCTs) and nutritional ketone esters (9), which can act as a precursor for ketone production.

Dietary ketones may be a helpful addition to cancer treatment; cancer cells often develop mutations that cause them to become totally reliant on rapid metabolism of glucose to sustain their proliferation and expansion. The decrease in blood glucose seen during ketosis and the inhibitory effect of ketones themselves on glucose breakdown could help to weaken tumors by ‘starving’ them of their only fuel source and make them more vulnerable to attack by standard anti-cancer treatments (10).

Conclusion

Whilst it is evident that ketogenic diets and nutritional ketones have a large role in the treatment of disease, such a diet may also be applied to the general population looking to maintain steady energy levels throughout the day and cut the ties that make us obligate consumers of carbohydrates.

Ketosis is not the answer for everyone. Perhaps one of the biggest challenges to the individual’s health is the medical community’s search for a ‘unifying dietary hypothesis’: a single diet that optimises the health of everyone in the population. The idea on inspection appears ludicrous@ Many people may benefit from following a ketogenic diet or consuming nutritional ketones, however there are an equal number of people who would not or who might experience negative outcomes.

To close, don’t be afraid to experiment whilst listening to your body to determine the best lifestyle choices for your changing health needs.

Written by Brianna Stubbs, Oxford University DPhil student in metabolic biochemistry

References:

  1. Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF. Brain Metabolism during Fasting. J Clin Invest 1967;46(10):1589-&.
  2. Cahill GF, Jr. Starvation in man. New Engl J Med 1970;282(12):668-75.
  3. Alberti KG, Hockaday TD. Rapid blood ketone body estimation in the diagnosis of diabetic ketoacidosis. Br Med J 1972;2(5813):565-8.
  4. Robinson AM, Williamson DH. Physiological Roles of Ketone-Bodies as Substrates and Signals in Mammalian-Tissues. Physiol Rev 1980;60(1):143-87.
  5. Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostag Leukotr Ess 2004;70(3):309-19.
  6. Cox P, Clarke K. Acute nutritional ketosis: implications for exercise performance and metabolism. Extr Physiol Med 2014;3(1):17.
  7. Kossoff EH, Krauss GL, McGrogan JR, Freeman JM. Efficacy of the Atkins diet as therapy for intractable epilepsy. Neurology 2003;61(12):1789-91.
  8. Gibson AA, Seimon RV, Lee CM, Ayre J, Franklin J, Markovic TP, Caterson ID, Sainsbury A. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes Rev 2015;16(1):64-76.
  9. Feinman RD, Pogozelski WK, Astrup A, Bernstein RK, Fine EJ, Westman EC, Accurso A, Frassetto L, Gower BA, McFarlane SI, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition 2015;31(1):1-13.
  10. Newport MT, VanItallie TB, Kashiwaya Y, King MT, Veech RL. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s disease. Alzheimer’s & dementia : the journal of the Alzheimer’s Association 2015;11(1):99-103.
  11. Poff AM, Ari C, Arnold P, Seyfried TN, D’Agostino DP. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. Int J Cancer 2014;135(7):1711-20.

 


Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s