Ketone Supplements: an Aid to Longevity?

Longevity is being studied extensively, and so are exogenous ketones. The interlinking between the two reveals therapeutic effects against aging.

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The human body functions as a result of various physiological, psychological, as well as biochemical activities taking place within. As we age, these internal activities also start faltering. While some of these can be attributed to our genetic makeup, other causes are usually tied to the lifestyle choices we make. The cell is the basic structure of the human body and is largely responsible for its comprehensive functioning. When dysfunctional cells start accumulating instead of being eliminated, they lead to the secretion of toxic compounds. This leads to chronic inflammation of blood vessels, impairment in cellular functioning, which can potentially be a trigger for diseases like diabetes, Alzheimer’s, other neurological disorders, cardiovascular diseases, mobility issues, and so on.

Such experiences not only affect one’s lifespan but also degrade their quality of life. We are reluctant to consider the prospect of living a long life, since it can be marred by chronic illnesses. Longevity is therefore aiming not only to increase the quantity of one’s life but to also fill those years with healthy life experiences, i.e. to improve one’s healthspan.

Ketone bodies

All the talk about leading a healthy life has led to people investing heavily in building themselves a diet to suit their particular requirements. This also includes the consumption of supplements to give them a boost towards their goal. A relatively new entrant in this section is the ketogenic diet and supplements. The premise of a keto diet lies in the switching up of the body’s primary source of fuel from glucose to beta-oxidised fatty acids. When the glucose in the body drops below the necessary level for converting it into energy, fat cells will free up fatty acids. These are then sent to the liver where they are oxidised in the presence of an enzyme, B-hydroxybutyrate dehydrogenase. This enzyme ultimately breaks down the fatty acids to form ketone bodies, and the process is known as ketosis.

The most prominent and abundantly present ketone body is the beta-hydroxybutyrate (BHB), which is circulated throughout the blood to different cells, to be utilised as fuel for their functioning. Under such conditions, the brain will also start relying on ketone bodies for its cognitive performance. The production of ketone bodies takes place in one of two ways: a) Endogenous ketosis, which is brought about by prolonged fasting, intense exercise, or a low-carb, high-fat ketogenic diet; and b) Exogenous ketosis, which can be achieved by the ingestion of ketone supplements containing ketone bodies such as the BHB. These come in the form of ketone salts, medium-chain triglyceride oils, and ketone esters. Their function is to produce a rise in blood ketones, and complement endogenous ketosis.

A regulated increase in blood ketone levels has shown several beneficial effects in countering terminal illnesses, which can be pivotal in the research against aging, and towards longevity. Read on to find out about the documented positive impacts of ketone bodies on some prominent agents of mortality.

Alzheimer’s disease

An increased concentration of ketone bodies in the blood has shown to exhibit certain positive effects on Alzheimer’s disease, a progressive neurodegenerative disorder causing cognitive impairment. Without any curative treatment, the disease, as it advances, leads to severe degradation of brain function, hampering both the healthspan and lifespan in humans. One of the features of Alzheimer’s is its negative impact on glucose utilization by the brain, which results in a deficit of energy being supplied to the brain. Since ketone bodies act as alternative sources of energy, raising blood ketone levels above the 0.2 micromolar concentration can help to transcend this block in glucose utilization by the brain.

In a study, therapeutic hyperketonemia was induced through regular ingestion of a ketone supplement containing BHB ketone bodies in a patient diagnosed with Alzheimer’s disease. Observations over various parameters were conducted over 20 months, which exhibited an improvement in behaviour, cognitive functioning, and performance of daily activities. Without making any dietary changes, being on a ketone supplement alone resulted in the patient becoming self-sufficient in his day-to-day activities.

Additionally, ketone supplements may also prove helpful against the accumulation of extracellular amyloid B-peptide, which results in cognitive impairment in individuals diagnosed with Alzheimer’s. In a study where male 3xTgAD mice were fed a diet consisting of BHB and (R)-1,3-butanediol, there were significant improvements in their cognitive functioning and a reduction in the deposition of amyloid B-peptide. This shows that ketone bodies have the potential to retard the progression of the disease.


Type-2 diabetes, commonly present in adults, severely affects one’s functional capacities, quality of life, and can even lead to premature mortality. Reduced insulin sensitivity in the body disturbs the regulation of blood glucose. There is a rise in blood glucose concentration due to the inability to make and secrete insulin. The low-carbohydrate ketogenic diet was found to be effective in bringing blood glucose levels close to normal in a group of adult rats when studied over a period of 8 weeks.

In another study comprising of obese patients with type 2 diabetes, a strictly followed low-carbohydrate diet showed marked improvements in 24-hour blood glucose profiles, increased insulin sensitivity by ~75%, and loss in weight due to the reduced calorie intake. A 2012 study also showed the beneficial effects of a low-carbohydrate ketogenic diet on obese patients with type 2 diabetes. The diet led to an improvement in glycemic control.

Ketone bodies act as the primary source of energy to the body when there is insufficient glucose supply, which would have otherwise been the default fuel. Since ketone bodies essentially replace glucose, they have a direct effect on diabetic conditions and symptoms. Improvement in insulin sensitivity will lead to re-stabilisation of glucose levels, consequently resulting in an improvement in one’s healthspan.

Cellular communication and gene expression

Cellular signaling is necessary to trigger an immune response, and for the release of growth and developmental hormones in the body, among others. Cells communicate between themselves through different pathways, via the release of ligands. These attach themselves to the relevant receptors, making it through to the destination cells, where a response is generated.

Histone is one such protein that binds itself to DNA and regulates its access. Its binding is then reduced by acetyl groups, which opens access to the DNA, allowing for proteins to be manufactured. Histone deacetylases (HDACs), however, disrupt the functioning of these acetyl groups, thereby closing off access to the DNA. An inhibitor is therefore necessary to keep the access open, by inhibiting the HDACs enzymes. A study examining ketone bodies as potential signaling metabolites has shown that ketone bodies are inhibitors of HDACs. As an inhibitor, ketone bodies have the potential to restore and protect cellular communications, which would have otherwise been closed off. This can be an endogenous route to the extension of lifespan as HDAC inhibitors are being used to treat cancer, cardiovascular diseases, and inflammation-related disorders.

Other important benefits of ketone bodies towards longevity

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is key for the growth of neurons, improvement in synaptic connections, and overall brain health, including prevention against death of neurons. Ingestion of exogenous BHB ketone bodies recently exhibited favourable changes in BDNF levels.

Additionally, metabolic health has been shown to have a direct consequence on mortality and related illnesses. Exogenous ketosis can help in the regulation of the body’s metabolic health, preventing the potential onset of certain terminal diseases.

What lies ahead

The market for ketone supplements is slowly opening up and expanding. As seen above, studies showcasing the positive impact of exogenous ketones on age-related factors will likely augment the interest shown in supplements like ketone salts and esters. The prospect of longevity can have a catalysing effect on the demand for ketone supplements, as a natural medium to fight against age-related adverse developments.

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