Hello, me again. Im going to talk about intermittent fasting. Is it good? Is it bad? Is it helpful for weight loss? Is it beneficial for anything else? Let's find out...
What is intermittent fasting? Essentially, its time restricted eating, where we have a window to eat, and a window to fast (not eat). Some common protocols we see are the the 16:8 (16 hour fasting window), or the 5:2 (two days of fasting - but people still eat low calories allowances, strangely. So not really fasting). There are numerous cases where Time Restricted Eating (TRE) and Continuous Energy Restriction (CER) yield the same results, and the argument is that either work, provided you are creating a calorie deficit. Some shallow minds will end the argument there, and put everything down to a calorie deficit. Unfortunately the discussion can go a little deeper than that.
When people talk about intermittent fasting, they believe the reason they lose weight is because of ketosis, where the body has depleted glycogen and the body must now burn fat for energy, which in part, is true, but again, its a little deeper than that. Is fat tissue the only other form of stored energy that can be used as an energy substrate? No. The big issue is that people don't understand the actual fasting process. When we do intermittent fasting, we are relying on the fact we need to get into a fasted state, to really receive the benefits of the fasted state, obviously. Otherwise, we wouldn't really being doing anything, simply just eating our calories in a certain window, calorie deficit or no calorie deficit. And this is where most people can clearly state that TRE vs CER reap exactly the same results, because more often than not, they are exactly the dame anyway. Why? Because it takes a lot longer than 16 hours for the average individual to enter a the post-absorptive state. And this is why when people carry out a fasting method, they are not really fasting. Literature clearly shows that the post-absorptive state is reached after 18 hours, and the truly fasted state not until 36-48 hours . This is also dependant on multiple variables. Many people that a are about to enter the fasting window, will make sure they have a nice big meal to mitigate hunger throughout the early period of the fasting window, which obviously just prolongs the ability of the body to enter the post-absorptive state, probably pushing 18 hours nearer 20. What is also an important variable is the fact different body types and sizes will have different physiological responses to nil food. The bigger the person, the bigger the stomach, the more food they eat, the more tissues having the ability to store energy means the longer it will take for the body to deplete all available energy. And lets be honest, people that commit to intermittent fasting are probably on the slightly bigger side, hence trying to lose weight. They probably won't be anywhere near fasted after a standard 16 hour fasting window. They especially won't be entering a fasted state on a 5:2 diet, where the 2 days of limited food still involve food consumption, digestion and higher insulin levels.
But wait... that doesn't mean fasting is pointless or bad, provided we enter the fasted state.
Mechanisms of action:
As previously stated, when we intermittent fast, we are aiming for ketosis. Anton et.al. have used the term “metabolic switch” to describe “the body’s preferential shift from utilization of glucose from glycogenolysis to fatty acids and fatty acid-derived ketones” (pg. 255). They point out that “ketones are the preferred fuel for both the brain and body during periods of fasting and extended exercise”  As the human body undergoes an extended period of time without food, adipose tissue lipolysis increases to produce more fatty acids and glycerol. The free fatty acids are transported to the liver where they are oxidized to β-hydroxybutyrate and acetoacetate. They are converted to energy through beta-oxidation. If you are familiar with the metabolic pathways, beta-oxidation is one of them and the outcome will always be a molecule named Acetyl-CoA. This is very important to understand in the realms of fat/weight loss because this is purely the result of reduced caloric intake and the metabolic pathways producing molecules that can be used to make energy. The only difference is we are getting the energy from fat tissue, instead of glycogen, or amino acids, or directly from dietary fat and carbohydrates. Remember we are still juts talking about the metabolic switch, no magical weight/fat loss tool, simply just the body needing to switch where it gets its energy from. So hopefully we understand that the ketones themselves are not magical for weight loss, the weight loss is simply a result of the reduced caloric intake, however the ketones may influence other systems that will indirectly and arguably aid fat loss chronically, in my opinion. In the case of ketosis alone, not necessarily in na intermittent, or fasted state, we can still produce ketones, and they can be extremely beneficial.
Firstly, two of the main reasons why ketones may be highly advantageous are the following.
Epilepsy: The ketogenic diet was first introduced for treating epileptic patients. Ketone bodies may have anti-seizure, anticonvulsant and neuroprotective properties.
Cognitive function: studies show improved memory, cognition and motor function, and in mice studies, it shows increased the amount of motor neurons in the tonal chord and preserved motor function.
Possible mechanics why we get positive response from ketone production and utilisation:
Ketone bodies have an antioxidant capacity within mitochondria by reducing cell death and ROS (free radicals). Fewer free radicals means less inflammation. Reactive oxygen species (ROS) are key signalling molecules that play an important role in the progression of inflammatory disorders . An enhanced free radical production generation causes endothelial dysfunction and tissue damage. The vascular lining plays an important role in passage of macromolecules and inflammatory cells into tissues from the bloodstream. Under the inflammatory conditions, oxidative stress leads to the opening of inter-endothelial junctions (junctions in the lining of vascular systems) and promotes the migration of inflammatory cells across the endothelial barrier. This can lead lead to tissue injury. Imagine we have large scale inflammation and tissue injury is certain organs/glands that help produce key hormones, and specific times to regulate blood sugar (pancreas) or mood (brain). If these tissues are damaged through excess inflammation, it will undoubtedly increase our chances of failed weight management. Im not saying ketones are the only anti-oxidant, that can prevent the effects of free radicals and regulate levels of inflammation, but we can clearly see how they would help in our pursuit of health.
Cell studies have shown ketogenesis turns on PPAR-gamma, a known anti-inflammatory molecule. Im not going to rewrite the whole previous paragraph in a different way to describe anti-inflammation, but I will explain one thing. Anti-oxidation and anti-inflammation are different. Anti-oxidants are as described above, but anti-inflammatories directly impact the inflammation process.
Ketone bodies may activate the Nrf2 pathway (Nuclear Factor-like 2), increasing mitochondrial glutathione. Nrf2 is the most important pathway to increase our natural and innate antioxidant defence. This pathway plays a huge role in oxidative stress. Nrf2 controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the physiological and pathophysiological outcomes of oxidant exposure.  Activating this pathway may be very beneficial for mitigating levels of oxidative stress.
Increased bOHB (beta-hydroxybutryate), one of 3 main ketones created by the liver (78% of total ketones) BOHB supports cognitive function; on low glucose levels the brain is starved of fuel which can lead to brain fog and difficulty concentrating, so this ketone can supply fast acting fuel for the brain with roughly 70% of its energy needs. It also exerts great neuroprotective benefits including a reduction in reactive oxygen species (free radicals) and reduced neuroinflammation. This ketone, along with another key ketone acetoacetic acid, can easily pass through membranes and the are a great source of energy for the body and brain. These ketones actually provide the brain as a more efficient source of energy than glucose.
Lastly, a very interesting study I came across actually did show improvements in metabolic conditions in humans. Halberg et al. evaluated insulin sensitivity by hyperinsulinemic euglycemic clamp in 8 heathy men, pre- and post-ADF (Alternate Day Fasting - another popular IF method) with 20 hours of fasting. Insulin-mediated glucose uptake was assessed by glucose infusion rate (GIR). GIR is essentially how fast your body uptakes carbohydrates, and obviously if that is too fast, people will enter hyperglycaemia, not ideal. The final clamp was performed after a 36 hour fast. Although subjects maintained stable weight, insulin sensitivity improved, as indicated by significant increases in GIR, adiponectin, and inhibition of insulin-mediated lipolysis. The same results were not seen in a 14 hour post-fast study. So the insulin sensitising effects of fasting are more towards 20hours fasting rather than closer to 14 (confirming my earlier explanation of entering true fasted states). Improving insulin sensitivity will indirectly, or you could say directly impacts how we partition, or don't partition our ingested nutrient. Insulin resistance individuals will experience less nutrients enter desired cells, and potentially induce weight gain (i'm not getting into insulin resistance today).
To conclude, intermittent fasting is not just about a calorie deficit, and if performed correctly can have many beneficial outcomes. Notice I didn't talk about autophagy, a wrongly considered process if we are talking about the effects of intermittent fasting alone. Autophagy is seen in many other scenarios. Fasting is very, very healthy, it's not all about weight loss. And remember the effects of fasting, albeit not directly associated with immediate weight/fat loss can have some seriously beneficial outcomes for your long-term health, long-term weight management, and just overall function and well being.
If you do decide to participate in fasting, please do so under the supervision of a professional, im not telling you to, i'm simply here to tell you the benefits, and that's not to mention the potential implications if someone is not suited to the task.
Published by Luke French, Health & Physique Specialist | 22nd January, 2021
Personal Trainer and health coach specialising in fat loss, body composition and performance in the local area of Tunbridge Wells, Sevenoaks, Tonbridge and Hildenborough.
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 Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126-1167. doi:10.1089/ars.2012.5149
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