12 Benefits of ketosis for Overall Health and Medical Conditons

by | Last updated: Aug 16, 2020 at 3:58PM | - Published on: Feb 9, 2020

Nutritional ketosis is a natural metabolic state for humans. A lot of research links ketosis benefits to blood sugar control, fat loss, mood control, cancer, epilepsy and more.

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Ketosis benefits for overall Health

Very low-carb ketogenic diets becoming more and more popular, and a lot more research is being done on the benefits of being in a state of nutritional ketosis. While there are many long-term benefits, there are a few that often rank at the top of most people’s list.

Fat loss

One of the most well-recognized benefits of following a ketogenic diet is its ability to help reduce stubborn fat, like the last rolls of belly fat. The primary reason why is because well-formulated ketogenic diets can rectify the energy partitioning away from fat storage and towards a leaner physique. It can also help normalize appetite by normalizing the hunger hormones ghrelin and cholecystokinin (CCK). Ghrelin is released from the stomach and intestines, with the highest levels occurring during a fasted state. After consuming a meal, ghrelin levels decrease in response to circulating nutrients. Ghrelin levels also increase significantly after weight loss, which is the reason why weight can be difficult to keep off — your hunger is raging! But being in ketosis helps to suppress the increase in ghrelin that is experienced after losing weight [1]. Studies have shown that a ketogenic diet leads to decreased amounts of circulating ghrelin and therefore decreased feelings of hunger.

Low insulin levels

If trying to get into a state of ketosis and insulin levels are excessively high, it will be virtually impossible; insulin suppresses the burning of fat and production of ketones in the body [2]. So in order to get into ketosis, insulin levels must be under control.

Chronically high insulin levels and disrupting the communication of intestinal molecules (i.e. incretin signaling) can lead to the bad kind of insulin resistance over time. This means that cells are unable or unwilling to take up vast amounts of glucose and amino acids anymore. As more and more insulin is needed to take up a given amount of glucose – a vicious cycle forms where more and insulin is needed over time. Then comes the point where the pancreas is no longer able to supply the required insulin, and so fasting blood sugars surpass 120 mg/dL. Or A1c exceeds 6.5%. At these levels, it’s known as type 2 diabetes. With the ketogenic diet, insulin requirements are dramatically lowered (normalized). This may effectively reverse type 2 diabetes.

Following a ketogenic diet is highly beneficial for reversing high insulin levels (i.e. hyperinsulinemia) and thus normalizing insulin signaling. Carbohydrates raise insulin levels more than the other macronutrients protein and fat. When a meal with fast digesting carbs is consumed (e.g pasta), your liver receives aberrant signals from the gut and fat tissue. These signals cause the liver to struggle with the appropriately release of moderate glucose levels into the bloodstream. As they blood sugar levels keep getting higher and higher, the pancreas has to compensate by secreting more and more insulin to normalize the levels. This leaves the body bathing in a lipogenic environment, one favoring fat storage over fat burning, and likely in a chronic inflammatory state as well.

When carbs are absent or only form a small part of the diet, as on a ketogenic diet, insulin levels do not fluctuate as drastically as they would if consuming a higher carbohydrate diet with fast absorbing sugars [3]. The keto diet doesn’t prevent the production of insulin outright – that would be deadly! Rather, it decreases it enough to allow the body to produce ketones and able to fulfill its other crucial roles without the excessive damage.

Improves cardiovascular health

As obesity becomes more prevalent in industrialized countries, the prevalence of cardiovascular disease has also steadily increased. Diets rich in carbohydrates, specifically those with fast absorbing sugars like flour and sugar, are consistently linked with robust mechanisms underlying the development of metabolic syndrome, a major contributor to the development of cardiovascular disease (CVD).

Studies have shown the keto diet to be particularly effective for fat-loss, but more specifically visceral fat-loss. Evidence shows that a keto diet can also be effective for improving biomarkers used to assess CVD, such as weight and body fat percentage, glucose homeostasis, A1c and lipid markers like LDL, HDL and triglycerides [4,5].

Mood stabilization

The switch from glucose to ketones to fuel the brain is the underlying thought as to why the ketogenic diet has so many profound neurological benefits. Many studies looking at brain metabolism support the case-reports and anecdotes suggesting keto can help with mood disorders such as bipolar disorder, anxiety, and depression [6,7]. The preeminent mechanism put forth to support these observations is that the brain improves its general redox state when in ketosis and relying less on glucose [8]. The way in which naturally occurring free radicals are produced when metabolizing ketones, as well as their inherent anti-inflammatory action, are also potential mechanisms explaining the seemingly beneficial effect of ketosis on mood disorders [9,10].

Improves cognitive function

Energy for the body comes in the form of ATP, which is produced primarily by mitochondria – although the brain has an unusually high need for glucose compared to other tissues. Areas of the body that need larger amounts of ATP to function have more mitochondria to supply this energy reliably. If the number of mitochondria increases sufficiently and their energetic output is improved, there is more energy for the brain to meet its high energy demands. Fasting is one way to up-regulate mitochondrial biogenesis (production of new mitochondria). Regular fasting helps to protect the brain as well as other tissues from developing cancerous cells, toxic buildup from regular metabolism and chronic inflammation derived from unavoidable environmental factors (e.g. pollution) [11].

The ketogenic diet also decreases oxidative stress, the major factor in mitochondrial damage. Chronic and excessive stress creates inflammation which is no longer helpful but damaging, in part because it can impair mitochondrial function [12]. As oxidative stress increases, so does the extent of the damage. And as the brain relies heavily on mitochondria, it is often the first to show signs of this. Compared with glucose metabolism, ketones have been shown to produce lower levels of oxidative stress, which means potentially less inflammation, better energy output, and improvements in cognitive function [13].

Increases metabolic flexibility

Metabolic flexibility is the ability of the body to switch between burning carbs and burning fat, or technically speaking, the capacity to match fuel oxidation to fuel availability. Having metabolic flexibility means that the body is able to use different fuel sources to power different activities. Mitochondria are the structures that ultimately turn most of food derived molecules into useable energy (ATP). So naturally, being metabolically inflexible denotes an issue with mitochondrial function.

Metabolic inflexibility can be caused by a few different things (not a complete list):

Dysfunctional mitochondria — Mitochondria that don’t function as they should will produce less energy than healthy mitochondria. If oxidative stress levels are high, it impairs the rate and ability at which they can produce energy.

Too few mitochondria — As energy is produced primarily by mitochondria, too few of them that don’t work properly severely limits the amount of energy that is produced and makes switching from carb-burning to fat-burning very difficult.

Insulin resistance — Insulin sensitivity and resistance are natural responses regulating how much energy a cell receives. This enables the body to ensure it doesn’t energetically underload or overload cells (just like electric circuits are built so as to avoid blowing up light bulbs). The problem is, insulin resistance can become maladaptive when constantly triggered due to damaging environmental factors (e.g. fast absorbing sugars, dysregulated circadian rhythms, air pollution…). When insulin resistant, the body has a harder time burning excess fat stores and using them for fuel, making it hard for you to seamlessly switch between fat and glucose.

The ketogenic diet, however, helps to improve metabolic flexibility via many of the aforementioned mechanisms. It improves insulin sensitivity, reduces oxidative stress and improves mitochondrial function. So long story short, when you are metabolically flexible, your body can use carbohydrates and fat for fuel.

Ketosis Benefits for Medical Conditions

One of the most well-researched areas with respect to the ketogenic diet is its ability to help combat chronic diseases. Whether it’s cardiovascular diseases, diabetes, or epilepsy, ketogenic diets have been shown to be highly beneficial for reducing and managing symptoms as well as potentially undergoing a complete reversal.

Epilepsy

One of the earliest uses for the ketogenic diet was as a treatment for epilepsy. Epilepsy is a neurological disorder that is marked by abnormal electrical discharges in the brain that cause seizures. These sudden episodes can range in intensity but are generally characterized by altered or decreased consciousness, convulsions and/or involuntary movements. Pharmaceutical drugs are often the first choice for treating epilepsy yet ketogenic diets have been proven time and time again to be very beneficial and hence highly successful.

While the exact mechanism remains largely unknown, several other mechanisms have been proposed [14,15,16,17]:

  • Changes in ATP production may increase neuron resiliency in the face of metallic demands during seizure episodes
  • Altered brain pH affects neuron excitability
  • Ketone bodies/fatty acids exhibit a direct inhibitory effect on ion channels
  • Altered amino acid metabolism favors the synthesis of GABA (an inhibitory neurotransmitter)
  • Enhanced mitochondrial function
  • Decreased reactive oxygen species
  • Gut microbial-derived amino acid blood levels

Metabolic syndrome

Metabolic syndrome is a condition characterized by high levels of visceral fat, elevated blood pressure, high triglycerides, elevated blood sugar, and elevated LDL; these symptoms greatly increase the risk of developing diabetes, heart disease, and stroke. Although LDL cholesterol was put on this list it no longer deserves its sport [18].

Studies have shown that being in a state of nutritional ketosis helps to improve markers of metabolic disease including HbA1c, lipids, high-sensitivity CRP, fasting insulin and glucose levels, and helps reduce overall body weight [19]. In turn, by improving biomarkers of metabolic syndrome, the disorder can be reversed.

Alzheimer’s disease

Alzheimer’s disease is a progressive cognitive disorder that slowly impairs an individual’s thinking and memory. One of the major features of this disease is a loss in the connections between neurons in the brain. While the cause of its development and progression is unknown, research shows a promising link to metabolic dysfunction as a key factor. Current research has shown a clear link between the development of Alzheimer’s disease and dementia with blood sugar regulation disorders, with insulin resistance and diabetes most strongly correlated.

Insulin resistance has been shown as a major contributor to cognitive decline. A recent study found a very clear link between blood sugar levels and neurodegenerative diseases. Researchers at the University of Bath have found that excess blood glucose causes damage to a vital enzyme — macrophage migration inhibitory factor (MIF) — involved in the inflammatory response at the early stages of Alzheimer’s through a process called glycation [20]. They found that disease progression could be linked to an increase in the glycation of the MIF enzyme.

While a few large-scale studies have been completed on the association between Alzheimer’s and the ketogenic diet, several smaller studies have shown positive results. A 2009 study of 152 patients with mild Alzheimer’s showed improvements in cognition after following a ketogenic diet for 45 days [21]. Additionally, higher blood ketones have been associated with improves in memory recall in a study of 20 patients diagnosed with Alzheimer’s disease or mild cognitive impairment [22].

Ketone bodies themselves have been shown to be neuroprotective, which bodes well as a potential treatment option or intervention for improving neurodegenerative diseases [23].

Cancer

Several studies have been conducted on the efficacy of the ketogenic diet as an adjunct therapy for cancer. As a cancer therapy, ketogenic diets (or fasting) reduce circulating glucose levels to starve the sugar hungry cancer cells. The rising blood ketones also serve as a good substitute fuel for normal cells who are also starved of glucose. Reducing blood glucose also helps to decrease insulin and insulin-like growth factor levels, both of which are important forces exacerbating cellular proliferation [24].

The evidence so far shows that all cancers have some degree of mitochondrial dysfunction, with some even showing a down-regulation of enzymes necessary for ketone utilization [25,26]. So when the body is fueling itself with a low glucose-to-ketone ratio (e.g. 1), there is much less fuel available for cancer to survive and replicate, but still great fuel for normal cells to survive and for our immune system to fight back.

The ketogenic diet is not a panacea though. It will not lower blood levels of the amino acid glutamine, the other fuel remaining circulating in our bloodstream beloved by cancer cells since they can ferment it for energy and ‘parts’ (e.g. new structural molecules) [27]. The ketogenic diet is part of the larger umbrella of metabolic therapies that are very promising cancer therapies.

Polycystic ovarian syndrome (PCOS)

PCOS is one of the most commonly diagnosed reproductive disorders among women of reproductive age. Symptoms are associated with high levels of testosterone and include irregular or absent menses, excess body hair, and infertility, as well as medical abnormalities like obesity, insulin resistance, hyperinsulinemia, type 2 diabetes, and dyslipidemia and metabolic abnormalities including elevated serum testosterone, insulin resistance, and poor cholesterol ratios [28].

PCOS can be reversed for all intents and purposes if insulin levels are lowered, improve insulin resistance is improved and hormonal imbalances are addressed. Currently, no pill can do this. Fat-loss is also key in reversing the disorder given that being obese increases the amount of tissue producing inflammatory signals.

As the ketogenic diet has proven successful for weight loss and improving insulin sensitivity, it may be beneficial for PCOS. In a small 12 subject study conducted on women aged 18-45 with a diagnosis suggestive of PCOS, following a ketogenic diet shower improvement in body weight, percent free testosterone, LH/FSH ratio, and fasting serum insulin [29].

Lou Gehrig’s disease (ALS)

Lou Gehrig’s disease, more commonly known as ALS, is a progressive neurological disorder that causes progressive wasting of muscles and leads to difficulties in speech, swallowing, mobility and even breathing.

As the ketogenic diet has been proven effective in protecting nerve cells and their ability to produce energy, it has the potential to improve symptoms associated with ALS. Research has proven that mitochondrial dysfunction plays a central role in neuronal cell death in ALS. This study looked at the effect of the principal ketone body BHB (D-β-3 hydroxybutyrate) and how it impacts the generation of energy (ATP) to exert its neuroprotective effects. While there are few human studies on the efficacy of the keto diet in ALS development, this rodent study showed positive results. It was the first study to show that the KD can alter the progression of ALS [30]. The effects may be due to the ability of ketone bodies to promoting better ATP generation by shifting towards another ‘path’ for energy production (i.e. bypassing something called Complex 1).

Last word

The list of benefits that are being attributed to being in nutritional ketosis is growing. In the medical literature it started with epilepsy but in the public’s eye, fat-loss is what it’s all about. It should come as no surprise given our current obesity epidemic. Nevertheless, it’s interesting to note that many people come to a ketogenic for the fat-loss but end up staying for other benefits relating to physical and mental health.

Written by Raphael Sirtoli, MSc Biology

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