The Effects of the Keto Diet on Health and Disease
Many of the things we hear about the successes or failures of the keto diet come from anecdotes by people who swear by it or have had a terrible experience with it. Instead of focusing on these anecdotes, let’s dive into the research. Before doing this, we need to understand carbohydrates (carbs) and why it makes sense to reduce or eliminate them in certain cases.
Nearly 30% of people in the world are obese and almost half of Americans are obese and this global obesity epidemic is predicted to rise as our diets become more revolved around refined carbs and sugars.7 As obesity increases, the incidences of cardiovascular disease and mortality increase.2
High-glycemic-index (GI) carbs spike blood sugar levels and insulin levels, similar to the pharmacokinetics of addictive drugs. Most high GI foods are refined carbs and sugars that the human body is not meant to consume and digest. Examples of these are high fructose corn syrup, simple white sugars, processed white flours, etc. To read more on the negative effects of these refined carbs on the brain and gut, check out my microbiome blog.
Your diet should be tailored towards your lifestyle. In this 6-week customized meal plan, I focus on your health to get you the results you want. I work most dietary lifestyles, including the ketogenic diet.
Similar to these addictive drugs, glucose and insulin alter dopamine concentration and lead to addiction-like cravings. Dopamine is a neurotransmitter that plays a role in the reward-motivation behavior and is known as the “fight or flight” neurotransmitter. If something makes you feel good, you are more likely to do it again and this is how most addictions evolve.
Blood glucose and insulin levels rise and fall quickly and this is associated with shifts in other metabolic fuels and hormones. These properties make high GI carbs a trigger for food addiction. However, fatty foods do not induce opiate-like withdrawal symptoms, as seen in sugar bingeing.8
Benefits of the Ketogenic Diet
Weight loss for those seeking it
The cause of weight loss on the keto diet is still highly debated and seems to be caused by several factors. Weight loss may be due to:
- Reduction in appetite due to more filling fats
- Suppression of appetite due to ketone bodies
- Reduction in lipogenesis (formation of fat) and increased lipolysis (the breakdown of fat)
- Greater metabolic efﬁciency in consuming fats
- Increased metabolic costs of gluconeogenesis. When not provided through diet, the body will synthesize glucose from amino acids obtained from protein either from diet or from muscle
It is crucial to understand that weight gain on the keto diet is due to a caloric surplus and not due to the diet itself. Many people fail to see results on the keto diet due to the misconception that the amount of calories consumed does not matter. As with any diet, a caloric surplus will cause weight gain regardless of the nature of the diet.
It is very difficult for individuals to maintain their body weight after fat loss. Prolonged diets cause an increase in hunger and a decrease in metabolic rates, resulting in a tendency to regain fat. A meta-analysis of 13 different studies found that individuals assigned to a keto diet achieved signiﬁcantly greater long-term reductions in body weight than in a high-carb, low-fat diet.9
A study found that metabolism slowed by more than 400 kcal/day on a low-fat diet while there was no significant decline in metabolic rate on the keto diet.10 This suggests that the quality of the calories consumed affects the number of calories burned.
Type 2 Diabetes
Insulin resistance is the primary cause of type 2 diabetes (T2D). The main feature of insulin resistance is the inability of muscle cells to uptake glucose. A person with insulin resistance will divert a greater proportion of dietary carbs to the liver where much of it is converted to fat.11 Hemoglobin A1C concentrations [HbA1C] higher than 6.5% in individuals is an indicator of T2D.
In an ongoing 5-year study, 80.2% of the participants demonstrated [HbA1C] of 7.6% and only 19.8% of the participants demonstrated [HbA1C] below 6.5%. After 10 weeks on the keto diet, 56.1% of the participants demonstrated [HbA1C] below 6.5%. The study also demonstrated the reduction and elimination of diabetes medications in 56.8% of participants.12 Glucose control improves not only because there was less glucose coming in, but also because insulin sensitivity improved.
Cardiovascular Disease and Cholesterol Levels
In humans, the keto diet has been associated with a significant reduction in LDL “bad” cholesterol and an increase in HDL “good” cholesterol. The keto diet may be associated with some improvements in some cardiovascular risk factors, such as obesity and HDL cholesterol levels, but many of these studies are limited by time. Most individuals considering the diet are overweight, so any sort of weight loss would be beneficial to their overall health. It is crucial that these individuals maintain their body weight after weight loss.2
The human body makes 80% of the cholesterol it needs and only 20% comes from diet. Considering this, dietary cholesterol is not the cause of high cholesterol, but genetics is. While cholesterol is crucial for the production of every cell and for survival, people with genetically high cholesterol have elevated levels of LDL which can form plaques and clog arteries. One of the concerns people have when on the keto diet is dietary cholesterol from fats. Extensive research does not show evidence that dietary cholesterol plays a role in the development of cardiovascular disease.13
DNA Damage and Stress
The three main ketones produced through ketosis are acetoacetate, acetone, and β-hydroxybutyrate (BHB). Ketones decrease oxidative stress, increase antioxidants and scavenge free radicals. Free radicals are reactive oxygen and nitrogen species that possess unpaired electrons. They are highly reactive and can cause damage to DNA. A high concentration of free radicals in the body leads to oxidative stress because the body is unable to regulate them, leading to a number of diseases.14
A balance between free radicals and antioxidants is necessary for life. Results from one study strongly suggest that ketone bodies improve post-traumatic brain injury through their antioxidant properties, and prevention of oxidative stress-mediated mitochondrial dysfunction. 15
Longevity and Mortality
Caloric restriction, without malnutrition, has been shown to increase lifespan. In one study, 12 months old mice were assigned to a keto diet and compared to mice on a control diet. The mice were either allowed to live their natural lifespan or sacrificed after 1 month and 14 months on the keto diet to study their health. The keto diet signiﬁcantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a keto diet displayed greater longevity. 7
The more time a mouse spends exploring new objects, the stronger its grip strength is and the longer it can hang, the healthier it is. As observed in Figure 1, mice on the keto diet experienced significantly greater grip strength and hanging strength as well as greater time spent exploring new objects. 1
Figure 1. “A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice” 1
In another study, the keto diet was observed to slow cognitive decline and preserves motor function in aging mice. This suggests that ketone bodies may be necessary to elicit an extension of healthspan.14
Can you Build Muscle on a Ketogenic Diet?
Although more long-term studies are needed before a firm conclusion can be drawn, it appears, from most literature studied, that the keto diet is protective against muscle protein degradation during energy restriction, provided that it contains adequate amounts of protein and high amounts of fat.16
When glucose levels are low in the body, gluconeogenesis takes place. In ketosis, ketone bodies are the primary source of energy, decreasing gluconeogenesis significantly. Considering this, the breakdown of proteins to synthesize glucose is also significantly decreased. This is observed by decreased nitrogen levels in the urine of fasted human subjects. Nitrogen in urine is a product of protein degradation. 17
- Roberts, M. N.; Wallace, M. A.; Tomilov, A. A.; Cortopassi, G. A.; Ramsey, J. J.; Lopez-Dominguez, J. A.; Roberts, M. N.; Wallace, M. A.; Tomilov, A. A.; Zhou, Z.; et al. A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice Short. Cell Metab. 2017, 26 (3), 539-546.e5.
- Kosinski, C.; Jornayvaz, F. R. Effects of Ketogenic Diets on Cardiovascular Risk Factors : Evidence from Animal and Human Studies. 2017, 1–16.
- Paoli, A. Ketogenic Diet for Obesity : Friend or Foe ? 2014, 2092–2107. .
- Shilpa, J.; Mohan, V.; Diet, M.; Centre, H.; Diabetes, M. Ketogenic Diets : Boon or Bane ? 2019, 148 (3), 251–253.
- Puchalska, P.; Crawford, P. A. HHS Public Access. 2018, 25 (2), 262–284. Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics.
- Manninen, A. H. METABOLIC EFFECTS OF THE VERY-LOW- CARBOHYDRATE DIETS : MISUNDERSTOOD “ VILLAINS ” OF HUMAN METABOLISM. 2004, 1 (2), 7–11.
- Christopher, J. L.; Danaei, G.; Ding, E. L.; Mozaffarian, D.; Taylor, B.; Ezzati, M. The Preventable Causes of Death in the United States : Comparative Risk Assessment of Dietary , Lifestyle , and Metabolic Risk Factors. 2009, 6 (4).
- Lennerz, B.; Lennerz, J. K. Mini-Reviews Food Addiction , High-Glycemic-Index Carbohydrates , and Obesity. 2018, 71.
- Bueno, N. B.; Sofia, I.; Melo, V. De; Oliveira, S. L. De. Systematic Review with Meta-Analysis Very-Low-Carbohydrate Ketogenic Diet vs. Low-Fat Diet for Long-Term Weight Loss : A Meta-Analysis of Randomised Controlled Trials. 2013, 1178–1187.
- Ebbeling, C. B.; Swain, J. F.; Feldman, H. A.; Wong, W. W.; Hachey, D. L.; Garcia-lago, E.; Ludwig, D. S. Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance. 2019, 307 (24), 2627–2634.
- Paoli, A.; Rubini, A.; Volek, J. S.; Grimaldi, K. A. Beyond Weight Loss : A Review of the Therapeutic Uses of Very-Low-Carbohydrate ( Ketogenic ) Diets. Eur. J. Clin. Nutr. 2013, 67 (8), 789–796.
- Mckenzie, A. L.; Hallberg, S. J.; Creighton, B. C.; Volk, B. M.; Link, M.; Abner, M. K.; Glon, R. M.; Mccarter, J. P.; Volek, J. S.; Phinney, S. D. A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level , Medication Use , and Weight in Type 2 Diabetes: 2 (1), 1–14.
- Soliman, A. Ghada. Dietary Cholesterol and the Lack of Evidence in Cardiovascular Disease. 2018.
- Lobo, V.; Patil, A.; Phatak, A.; Chandra, N. Free Radicals , Antioxidants and Functional Foods : Impact on Human Health. 2010.
- Greco, T.; Glenn, T. C.; Hovda, D. A.; Prins, M. L. Ketogenic Diet Decreases Oxidative Stress and Improves Mitochondrial Respiratory Complex Activity. 2016.
- Boison, D.; Stone, R.; Neurobiology, D. New insights into the mechanisms of the ketogenic diet. 2018, 30 (2), 187–192.
- Manninen, A. H. Nutrition & Metabolism Very-Low-Carbohydrate Diets and Preservation of Muscle Mass. 2006, 4, 4–7.
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