Ketones: Helping You Achieve Optimal Health & Wellness

Health, as defined by Webster’s dictionary, is “the condition of being sound in body, mind, or spirit… freedom from physical disease or pain… the general condition of the body.”[1]  Wellness is an active pursuit to maintain and improve health, particularly through diet and exercise. Adapting the human body to an alternative, more efficient fuel source (ketones) may be an ideal way of achieving health and wellness. In this paper, the term “ketone” is a biological reference to one or all of the three main ketone bodies produced by the liver via beta-oxidation: acetoacetate (AcAc), acetone (Ac), and beta-hydroxybutyrate (BHB). [2] BHB is the primary ketone in the blood and has been shown to have many beneficial effects on the human body.

Ketones are viable sources of energy, and are produced by the liver during times of fasting, strenuous exercise, eating a low-carbohydrate/high-fat diet, and through ketone supplementation. A state of ketosis (becoming keto-adapted) is signaled by a rise in blood ketone levels. [3] During ketosis, ketones not only replace glucose as the primary energy source that the body uses, but ketones may actually be preferred over glucose by some of our most vital organs: the brain, the heart, and skeletal muscle. [4, 5, 6] Nutritional ketosis (natural physiological state when the liver is producing ketones due to a high-fat diet) offers a vast array of potential benefits for health and well-being, including weight loss, increased satiety, and optimized mental and physical performance. There is also growing evidence that ketone supplementation and/or lowering dietary carbohydrate intake and switching to ketone metabolism through nutritional ketosis may protect the body from many common ailments.

1. Decrease Blood Sugar/Insulin Spikes and Crashes

Most low-fat diets are also low-calorie diets, which can lead to cravings and constant hunger. It is also quite common to have difficulty maintaining weight loss after following these diets. On low-fat/high-carbohydrate diets, the body is using glucose as its main fuel source. However, the body has limited storage capacity for glucose, and, thus, hunger can kick in quite rapidly. As blood glucose sharply increases following high carbohydrate consumption, insulin also rises to transport glucose from the blood stream for storage/use. Blood sugar fluctuations result in characteristic highs and crashes. [7] Common side effects of these fluctuations [8] include:

• Nausea
• Headache
• Mood swings
• Extreme hunger
• Weakness/Dizziness

During nutritional ketosis, the peaks and valleys of both glucose and insulin responses to food level out; fasting blood glucose decreases and insulin levels drop dramatically. [9, 10, 11] 

2. Lose Weight, not Muscle

Weight loss is routinely observed in patients that are following a high-fat, carbohydrate-restricted diet. [5, 10, 11, 12] Weight loss occurs initially through water loss due to increased excretion of sodium and potassium. Fat loss follows as the metabolic machinery switches from using glucose to using ketones as fuel. As a natural reaction to low blood levels of glucose, the body will not only use dietary fat for fuel, but will also recruit fat from storage, converting triglycerides to ketones in the liver.   Moderate amounts of protein are consumed with a typical ketogenic diet and, therefore, lean mass is preserved, while fat is lost. [13, 14]  This muscle-preserving effect has also been seen with BHB supplementation rather than through dietary means. [15, 16, 17]

3. Suppress Appetite and Improve Satiety

Satiety and appetite are physiological opposites, so generally speaking, satiety is the same as appetite suppression. Satiety is another response to ketogenic dieting that is regularly reported. [18] The root causes for satiety are complex. Both fat and protein have been reported to induce satiety (a feeling of fullness, a desire to stop eating).  Reductions in blood sugar fluctuations are also believed to play a role through the complex interactions of glucose-insulin-ghrelin-leptin. [19] Additionally, elevated blood BHB levels are linked to satiety. In a study where sodium BHB was given orally and intravenously to obese patients undergoing 14 days of therapeutic starvation, none of the patients had hunger complaints. [20]

4. Fuel Your Brain the Way it Prefers

Though the human brain accounts for only 2% of body weight, it consumes 20% of the body’s total energy requirements. [21] While glucose is the fuel of choice for the brain during high carbohydrate eating, the brain can readily use ketones for energy, and it has been suggested that brain cells preferentially use these molecules over glucose. [3] Nutritional ketosis tips the balance in favor of ketones as the predominant fuel in the blood stream. However, ketone supplementation can also raise the concentration of ketones, such as BHB, in the blood and can fuel the brain even in the presence of glucose. [4, 22]

There is increasing interest in both healthy populations and specific patient populations regarding ketosis and improvements in brain function (cognition).  Increasing blood ketones through supplementation with medium-chain triglycerides (MCT oils are typically derived from coconut oil) has been shown to improve cognition in older adults. [23] Similarly, the ketogenic diet has been shown to improve cognition in children with epilepsy. [24] Individual reports of improved focus with ketone supplementation in humans abound. In research studies, ketone supplementation has also been shown to improve working memory in rodent models. [25] Clearly, more study is warranted to understand the role of ketones and cognition.

5. Reduce Stress and Improve Mood

A key indicator of health is to be sound in body, mind and spirit. Psychological stress antagonizes each of these and, as such, is a major indicator of health and wellness.  Diets high in carbohydrates can exacerbate stress due to blood glucose fluctuations.  In a clinical study, subjects given supplemental BHB had lower peak adrenaline, noradrenaline, cortisol and growth hormone responses during hypoglycemia. [26] Elevated levels of the aforementioned hormones are all linked to stress. There are also several reports from clinical studies of ketogenic diets showing improved mood. [27, 28, 29]

6. Optimize Physical Performance

Several clinical studies have demonstrated the protein-sparing effect of the ketogenic diet in humans [15, 16, 17], emphasizing that even though nutritional ketosis can promote weight loss, it doesn’t necessarily mean that muscle mass will also decrease. Nutritional ketosis and low carbohydrate approaches combined with moderate protein intake and exercise can be effective tools in reducing body fat while increasing muscle mass. Supplementation with BHB has also demonstrated muscle building and sparing effects in humans, specifically through attenuation of leucine oxidation and promotion of protein synthesis. [6] BHB supplementation showed reduced net body protein loss in obese patients undergoing therapeutic starvation for 14 days. [20] Another potential benefit of ketone supplementation is decreased respiratory exchange ratio, a good indicator of overall fitness that measures the ratio of carbon dioxide production to oxygen consumption. [63] Not only can this improve endurance, but it may also benefit patients with respiratory failure. [63]

7. Minimize Risk of Diabetes, Insulin Resistance, Metabolic Syndrome, and Obesity

As previously mentioned, blood sugar fluctuations from a high-carbohydrate diet can create a number of issues. Chronic high blood sugar levels may lead to type 2 diabetes, cardiovascular disease, and other serious medical conditions. [30] The risk for these ailments is significantly decreased by adapting to a ketogenic metabolic state. [3, 10] One important thing to note is that ketosis is often confused/associated with a life-threatening medical condition called diabetic ketoacidosis (DKA). During DKA, the patient will have both high ketone and high blood sugar levels, unchecked by insulin. [2] This is very rare, and usually will only occur in those with uncontrolled type 1 diabetes. [2] Patients with type 1 diabetes may still benefit from low-carb diets, but it is crucial to consult a physician to monitor blood sugar and ketones on a regular basis.

• Diabetes/Insulin Resistance: Ketosis can reduce blood sugar and corresponding insulin fluctuations, lower fasting blood sugar, and protect from the negative effects of low blood sugar. Ketosis has also been shown to increase insulin sensitivity and improve glycemic control. [11, 12] In one study, obese patients with type 2 diabetes were put on a low-carbohydrate/high-fat diet and saw improved insulin sensitivity, hemoglobin A1C, and decreased triglyceride and cholesterol levels. [10] More long-term studies need to be done to establish nutritional ketosis as a part of diabetes management.
• Metabolic Syndrome: According to the National Heart, Lung, and Blood Institute, metabolic syndrome is “a group of risk factors that raises your risk for heart disease and other health problems, such as diabetes and stroke.” [31]  There are five risk factors associated with metabolic syndrome: large waistline, high triglycerides, low HDL, high blood pressure, and high fasting blood sugar. Co-occurrence of any three indicates metabolic syndrome. Nutritional ketosis has been shown to positively impact all factors including weight loss [5, 10, 11, 12], decreased triglycerides [10], increased HDL [32],  decreased blood pressure [32], and decreased fasting blood sugar. [11]
• Obesity: Many clinical studies have evaluated the ketogenic diet for its effects on obesity. [33] The induction of nutritional ketosis has both physiological and biochemical support and consistently induces weight loss. The available evidence points to reduced appetite/increased satiety [34, 35, 36]; reduced fat storage and increased fat breakdown [37, 38]; increased metabolic use of fats [29, 39, 40];  the thermic effect of proteins [41]. Supplementation with BHB during a ketogenic diet study in obese patients reduced net body protein loss, increased the fat/lean ratio of the tissue loss, while preventing hunger. [20]  Similarly, studies have demonstrated the muscle-sparing effects of BHB supplementation during weight loss trials with obese patients. [15, 16]

8. Improve Cardiovascular Health

When looking at the long-term effects of a ketogenic diet in obese patients, it was demonstrated that ketosis resulted in decreased triglyceride levels, increased “good” HDL cholesterol, lowered “bad” LDL cholesterol levels, and decreased blood glucose. [5] In this clinical study, a low-carbohydrate/high-fat diet improved biomarkers that are indicators of cardiovascular disease, contradicting the idea that all fat causes heart disease. [42] Healthy fats (saturated, monounsaturated, and some natural polyunsaturated) in combination with carbohydrate restriction can decrease the risk of heart disease. Excess stored fat (body fat) and intake of unhealthy fats (trans and processed polyunsaturated) can increase the risk of heart disease. Elevated free fatty acids can mediate insulin resistance and are observed in obesity. [43]  Lowering of blood pressure is also commonly observed in patients in ketosis/on a ketogenic diet. [44]

Additionally, BHB supplementation in healthy humans consuming a standard American diet caused a decrease in free fatty acids in the blood, as well as decreased blood glucose production. [45]

9. Hope for Tomorrow – Recent Medical Research

The ketogenic diet and ketone supplementation have been extensively studied in both basic research settings as well as in human clinical trials for several major diseases. A growing body of evidence shows that ketosis is a viable approach to avoiding complications from a variety of ailments.

• Seizures: The ketogenic diet has been used for decades to treat drug-resistant childhood epilepsy [46] and is currently used in multiple epilepsy centers throughout the world. [47] Evidence from animal studies indicates that ketone supplementation may be efficacious in attenuating seizures. Ketone supplementation has been shown to attenuate seizure activity in an Angelman syndrome mouse model [48], as well as delay CNS oxygen toxicity seizures in rats. [49]
• Polycystic Ovary Syndrome (PCOS): A recent pilot clinical trial indicates that ketosis can result in many improvements for women suffering from PCOS, a disorder associated with insulin resistance, obesity, and diabetes. [50]
• Migraines: Another pilot clinical study demonstrated that ketosis is helpful in the management of migraines and can reduce their frequency. [51]
• Neurodegenerative Diseases: Human clinical studies with MCT ketogenic supplementation showed improvements in memory in adults diagnosed with mild cognitive impairment. [52] Animal studies have demonstrated that BHB is energy-sparing in the brain and has been cited to be neuroprotective against Alzheimer’s and Parkinson’s diseases. [53] Ketones have also been shown to be neuroprotective during hypoxia in animal models by depressing glucose uptake and consumption. [54, 55]
• Cancer: Ketones exhibit anti-cancer effects, as shown in animal models and human tumor cell lines. [56, 57, 58] Positive results using the ketogenic diet have also been observed in case studies of individual humans [59, 60], but more research needs to be conducted to ascertain whether cancers are responsive to ketosis/ketones or if ketosis is helpful as palliative or adjuvant therapy. [61]
• Wound Healing: Ketones have further medical application in wound healing. This is likely due to their ability to improve blood flow and decrease oxidative stress as demonstrated by ketone supplementation in animal models. [62]

Conclusion

Collectively, scientists, nutritionists and physicians recommend reductions in sugars and processed carbohydrates for a healthy diet. Going one step further, very low carbohydrate/ketogenic diets also have potential positive impacts on health and wellness. More recently, the addition of ketones through dietary supplementation with ketogenic foods (coconut or MCT oils) or with ketone supplements, such as BHB, have been linked to positive health outcomes. Many of the advantages of ketones as a fuel source have been well documented, while there are others that still need more research. The Keto Advocate’s YouTube channel contains interviews of top researchers and physicians covering ketosis, the ketogenic diet, and ketone supplementation for health, wellness, and disease support. 

It is important to consult a physician before making any significant dietary changes, especially if you have a pre-existing medical condition.

References