In the previous episode, we have briefly discussed the short history and current practices of ketogenic diet (KD). To refresh our mind, KD supplies the energy mostly from fat instead of carbohydrate. Besides that, we have also discussed how easy it is to adopt KD as one of the reasons many people choose to follow this method of diet. In this episode, we will dive deeper to see the physiological impact of KD to our body.
Ketogenic diet and weight loss
When following a KD, carbohydrate starvation leads to physiological state called ketosis [1], which can also be found during fasting. Ketosis is normally achieved after a few days in which the body's glucose reserves become insufficient for the production of oxaloacetate for normal fat oxidation in the Krebs cycle and the supply of glucose to the central nervous system. During ketosis, the body use ketones (e.g., beta-hydroxybutyrate, acetoacetate, acetone) as a substitute for glucose to be the source of energy. The mechanism by which weight loss is achieved is yet to be established. It is also not entirely clear if the weight loss is simply due to water loss. Some suggested mechanisms are listed below in order of importance and available evidence [2]:
Reduction in appetite due to higher stiety effect of proteins, effects on appetite control hormones, and to a possible direct appetite-suppressant action of the KBs.
Reduction in lipogenesis and increase lipolysis.
Reduction in resting respiratory quotient and, therefore, greater metabolic efficiency in consuming fats.
Increased metabolic costs of gluconeogenesis and the thermic effect of proteins.
Ketogenic diet and metabolic health
Some studies have shown that KD evidently to be beneficial for type 2 diabetes (T2D), metabolic syndrome, as well as improving cardiovascular risk [2-4]. It has also been reported that KD cause a rapid and sensible weight loss along with favorable biomarker changes, such as reduction in serum HbA1c, the glycated haemoglobin, as well as adiponectin and markers of insulin sensitivity [5].
However, apart from these recognized benefits, KD also causes substantial rise in (apoB) low density lipoprotein (LDL) cholesterol levels [5] and many physicians are therefore hesitant to endorse this method of diet. Controlled studies comparing low-fat versus low-carbohydrate diets did not demonstrate the superiority of either dietary approach for weight loss. Compared with a low-fat diet, a low carbohydrate diet program had better participant retention which might result in the greater weight loss in 24 weeks. During active weight loss, serum triglyceride levels decreased more and high-density lipoprotein cholesterol level increased more with the low carbohydrate diet than with the low-fat diet [6].
The bottom line is that despite its current popularity, we have very few studies that can support or refute its impact on health. The National Lipid Association Nutrition and Lifestyle Task Force reviewed all the available evidence in 2019 and found low and very-low-carb diets are not superior to other dietary approaches for weight loss [7]. Regardless of benefits in terms of weight loss and glucose control at the beginning, compared to other diet approaches, the gap diminishes and is no longer statistically significant the longer KD is adopted.
On the other hand, KD has also been shown to promote higher fat deposition, inflammation marker C reactive protein [5], and liver fat [8]. Noteworthy, most interventions were only conducted in the short term [8], so assessment for a long-term impact is warranted. Hence, plant-based diets allowing a moderate daily content of non-saturated fats, and low intake of red meats and saturated fats hold for now the best epidemiological and randomized clinical trial evidence for being safe, effective, as well as sustainable [9].
S.A.D Team
Reference
Ludwig DS. The Ketogenic Diet: Evidence for Optimism but High-Quality Research Needed. The Journal of Nutrition 2019. doi: 10.1093/jn/nxz308.
Paoli A, Rubini A, Volek J, Grimaldi K. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European journal of clinical nutrition 2013;67(8):789-96.
Paoli A. Ketogenic diet for obesity: friend or foe? International journal of environmental research and public health 2014;11(2):2092-107.
Athinarayanan SJ, Adams RN, Hallberg SJ, McKenzie AL, Bhanpuri NH, Campbell WW, Volek JS, Phinney SD, McCarter JP. Long-term effects of a novel continuous remote care intervention including nutritional ketosis for the management of type 2 diabetes: a 2-year non-randomized clinical trial. Frontiers in endocrinology 2019;10:348.
Rosenbaum M, Hall KD, Guo J, Ravussin E, Mayer LS, Reitman ML, Smith SR, Walsh BT, Leibel RL. Glucose and Lipid Homeostasis and Inflammation in Humans Following an Isocaloric Ketogenic Diet. Obesity 2019;27(6):971-81. doi: 10.1002/oby.22468.
Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Annals of internal medicine 2004;140(10):769-77.
Kirkpatrick CF, Bolick JP, Kris-Etherton PM, Sikand G, Aspry KE, Soffer DE, Willard K-E, Maki KC. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. Journal of clinical lipidology 2019;13(5):689-711. e1.
Luukkonen PK, Dufour S, Lyu K, Zhang X-M, Hakkarainen A, Lehtimäki TE, Cline GW, Petersen KF, Shulman GI, Yki-Järvinen H. Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease. Proceedings of the National Academy of Sciences 2020;117(13):7347-54. doi: 10.1073/pnas.1922344117.
O'Neill B, Raggi P. The ketogenic diet: Pros and cons. Atherosclerosis 2020;292:119-26.