(Low Carbohydrate Diets) LC

In my last article I talked about some of the research around LC diets and their influence on weight loss. However, there was one aspect which I didn’t talk about and that was ketones. I am sure you have all heard the word ketones floating around in the fitness world and when it comes to LC diets and weight loss, ketones seem to be a pretty big deal. So, in this article I want to address what ketones actually are, how they are produced and where they fit into the whole weight loss picture. 

No More Glucose! What Is The Evolutionary Response To An Energy Crisis?

Ok, so you all know that glucose is the major energy source for the body. No glucose, no energy for the body to power all of it’s processes. When glucose levels drop (e.g. through exercise, fasting, LC diets), the body needs to find an alternative source of energy. Fatty acids can come to the rescue and can act as an alternative energy source for many of the tissues, except one: the brain! So what happens then? The brain can’t use fatty acids for its energy and so when glucose starts to drop, the body will produce ketones. This helps spare any remaining glucose needed for the brain, while ketones can be used as the alternative energy source to keep powering the other body tissues. 

Ketogenesis: The Process (Simplified!)

In LC diets, the lack of glycogen stores and thus glucose over time can drive the body to utilise alternative sources of energy. This is supposed to be the beauty of LC diets, there is a switch from carbohydrate utilisation to fatty acid utilisation. So basically the theory is, LC diets force your body to tap more into its fat stores for energy production. Sounds pretty good, right? More fat utilised, more fat loss! There will also be an increase in utilisation of amino acids and glycerol through gluconeogenesis in order to provide sufficient glucose for red blood cells and the central nervous system. But it’s not enough by itself and also, you don’t want to utilise all your precious muscle tissue to provide the body with all its energy!

ltc-ead_nutes_ufrj_br_constructore_objetos_artigo_206_20-_20Cahill_202006_pdf.jpgCahill (2006). Figure shows the increase in B-hydroxybutyrate (ketone body) when glucose levels drop. There is an increase in free fatty acids when insulin levels drop, and these fatty acids are mobilised to increase ketone body production (as evidenced by the increase in B-hydroxybutyrate as insulin and glucose levels fall).

ltc-ead_nutes_ufrj_br_constructore_objetos_artigo_206_20-_20Cahill_202006_pdf.jpg

Cahill (2006). Figure shows the drop in ketone production (B-hydroxybutyrate) when glucose is administered (black arrow). In the presence of sufficient glucose, ketone production is reduced. 

So this is what happens: the body sets ketogenesis into full throttle. On a LC diet, the levels of circulating insulin will be lower and the levels of glucagon (hormone released by the pancreas) higher. Under normal circumstances, insulin is used to maintain the levels of glucose in the blood. As the levels of glucose rise, insulin is released to shuttle that excess glucose into the cells. It keeps your blood sugar levels nice and steady! Likewise, when your levels of blood glucose drop, glucagon release from the pancreas will be stimulated. Glucagon then enhances the breakdown of glycogen to glucose, activates gluconeogensis (amino acid conversion to glucose) and stimulates breakdown of stored fat (triglycerides) into free fatty acids. However, both lower levels of insulin and higher levels of glucagon during LC diets will act to stimulate the mobilisation of fatty acids which then can act as the substrates for ketogenesis. 

Once these fatty acids have been mobilised from triglycerides (stored fat), they can then be utilised to produce Acetyl-CoA (through fatty acid oxidation). But that is not all! There is another important player in all of this: Oxaloacetate. Now, Oxaloacetate is given two choices: it can either combine with Acetyl-CoA to allow Acetyl-CoA to enter the citric acid cycle (the production of ATP by oxidation of Acetyl-CaA) or, it is utilised in the process of gluconeogenesis (ATP production from amino acids). Thus the route taken by Oxaloacetate will depend on the levels of glucose. If the levels of glucose are high, then Oxaloacetate will combine with Acetyl-CoA for the citric acid cycle.

Why? Glucose is used in the process of glycolysis to produce pyruvate (ATP is released in the process). Pyruvate is needed for the production of Oxaloacetate. If glucose levels start to drop too low, then glycolysis starts to fall. Subsequently, there is less pyruvate available for the production of Oxaloacetate. Since glucose needs to be conserved for the brain in desperate times and there needs to be another available energy source for the rest of the body as well, there would be no point allowing glycolysis to carry on at its current rate. You don’t want to use up the every last drop of glucose that the brain needs! Therefore, the remaining Oxaloacetate available will be diverted to gluconeogenesis (rather than combining with Acetyl-CoA). This will allow the Acetyl-CoA to be diverted from the citric acid cycle, towards the production of ketones (in the liver).

Even when there is no more glucose left to spare for the brain, ketones can still be utilised to provide the brain with its energy requirements. But really, this is the last-resort scenario for the brain.

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The Benefits Of A Ketogenic Diet?

So there are a few ways that ketogenic diets might exert their weight loss-inducing effects (Paoli, 2014):

•Higher Protein Intakes, Gluconeogenesis And The Thermic Effect Of Food•

With the reduction in carbohydrates in ketogenic diets, protein intake is usually increased to make up the lost energy requirements. Deriving energy from protein is a metabolically ‘expensive’ process (high thermic effect of food). It takes a lot more calories to extract the energy from it than from carbohydrates and fats. As a result, not all the calories you consume on a ketogenic diet will be utilised by the body. Some of those will be wasted in trying to digest the extra protein. These wasted calories are likely to lead to the increased weight loss seen in comparison to other ‘less expensive’ diets (e.g. those that utilise primarily carbohydrates as the main energy source). 

Also, given that glycogen stores and glucose levels will suffer from larger depletions from a ketogenic diet than in comparison to a moderate/high carbohydrate diet, the body will start to ramp up gluconeogenesis (mobilisation of amino acids to produce glucose) in order to supply the body with its glucose needs. This is usually a very energy demanding process and is likely to cost you a few hundred extra calories per day. 

•Protein And Ketone-Induced Appetite Suppression•

Appetite suppression might occur through two mechanisms: through protein itself. Protein has greater effects on satiety than carbohydrates and fats. People following ketogenic diets are therefore likely to experience lower levels of hunger and through this consume less total calories, than with diets consisting of higher amounts of carbohydrates.

It’s also likely that ketones themselves might have a direct effect on appetite suppression through mediating changes in the release of various hormones responsible for regulating hunger and satiety, particularly Ghrelin. 

•Reduction In Lipogenesis And Increased Lipolysis• 

A reduction in circulating levels of insulin and an increase in glucagon in ketogenic diets results in an increase in the mobilisation of fatty acids from triglycerides (stored fat). These fatty acids can then be utilised by the mitochondria in the liver to produce ketone bodies. 

•Greater Metabolic Efficiencies•

As highlighted by Veech (2004), ketones seem to impact significantly mitochondrial energetics. Basically ketones are able to influence mitochondrial ATP production in a way that results in an increase in energy output. An increase in energy output is therefore likely to lead to more calories being expended. 

PubMed_Central__Figure_1__Eur_J_Clin_Nutr__2013_Aug__67_8___789–796__Published_online_2013_Jun_26__doi_ _10_1038_ejcn_2013_116.jpg

 

Paoli et al (2013). Figure shows some of the potential effects that ketogenic diets have on weight loss (and other areas). 

Is Ketosis Really Dangerous For Us?

When you type in ketosis on the internet, you usually come across things like ‘diabetic ketoacidosis’. Now, diabetic ketoacidosis is pretty bad news! In this case, if you can’t produce enough insulin, then you can’t shift enough glucose from your blood into your cells for energy. As a result, the body starts to break down fats which are used to produce the ketones to fill this energy gap. However, in this circumstance, blood ketone concentrations can exceed 25 mmol/L and blood pH can decrease below 7.3 (become more acidic) (Noakes and Windt 2017). That all signals bad news indeed! If left untreated, can lead to hypovolemia (loss of blood volume caused through increased urinary loss of water, sodium, potassium and glucose). It’s therefore understandable that lots of people see ketosis through dietary manipulation as undesirable. 

However, as Veech et al. (2001) points out, blood ketone levels can reach 7-8 mm/L in fasting individuals. Given that episodic starvation was a normal state during the hunterer-gatherer times, the production of ketones would have served as an essential survival mechanism to spare the bodies muscle mass while continuing to serve the brains energy requirements. As Veech. et al. (2001) says ‘’the survival benefit is obvious: about 2 months for an average weight starving adult compared to a calculated 2-3 weeks were ketones not available’’. In other words, ketone production is really just a temporary survival mechanism during starvation periods until glucose becomes readily available again. It’s not a long-term sustainable solution. This brings into question whether ketogenic diets (even though there seems to be benefits in the literature) are really meant for the long-term?

Given that ketosis represents a state of starvation, the body is likely to switch on behavioural mechanisms that shift ones desire to eat. This desire is likely to make ketogenic diets unsustainable over the long term. Over the short term, yes, these diets might provide substantial weight loss benefits, but given that the body is actually in a state of starvation, intense desires for food (especially carbohydrates) are likely to make the success of such a weight loss approach harder (and possibly dangerous) over the longer-term. 


Next article will look at the role of ketones in exercise performance! Stay tuned