A Look at the Keto Diet
An In-Depth Look at the Keto (Low-Carb) Diet
Joy Stepinski, MSN, RN-BC
February 25, 2023
Introduction
According to the Centers for Disease Control and Prevention [1], obesity has a prevalence of 41.9% in the pre-pandemic years of 2017 – 2020. Adding overweight to that number and the prevalence jumps to 73.6%. Overweight is defined as having a body mass index (BMI) of 25 – 29.9 and obesity of 30 – 39.9. Worldwide obesity rates have tripled since 1975 [2], and according to the World Health Organization most people live in countries where overweight and obesity kill more people than being underweight. In order to lose weight, people often look for solutions. Many attempt a low-carbohydrate, high-protein, high-fat diet as a way to lose weight, often enamored by the messages of popular diet books and speakers that promote this way of eating. Popular low carb fad diets include the ketogenic diet or the Atkins diet. This article will explore the benefits and drawbacks of the low-carb diet.
What is a ketogenic (keto) diet?
A ketogenic diet is a way of eating that causes the body to enter into a chronic state of ketosis [3]. The body primarily uses glucose as a source of energy. However, in certain circumstances, such as starvation, a different metabolic state can be used. This provides a different energy source and a mechanism to aid in survival. Instead of glucose, ketones are utilized. During the 19th century, medical professionals discovered ketone bodies in the blood and urine of diabetic patients. This led to investigations that concluded later in the 20th century that although the brain largely used glucose and oxygen as a form of energy, under certain conditions it could also use ketone bodies for fuel.
A low-carbohydrate, moderate protein, and high-fat diet can lead to the metabolic state of ketosis [4] and cause ketone bodies to be produced. In research, urinary ketones can determine if a patient achieves ketosis. When glucose is not available, fatty acids are released from fat stores. The body attempts to use protein in creating glucose instead of using it for tissue repair. The liver converts the fatty acids into ketones. Thus, the body enters into a metabolic state of ketosis.
Literature
In one randomized controlled trial [5], the authors investigated the outcome of patients (n = 63) consuming a low-carbohydrate, high-protein, high-fat diet versus a “conventional” low calorie, high-carbohydrate, low-fat diet. Subjects were randomly assigned to one of the diets and were followed over the course of one year. Various measurements were taken, such as blood, urine ketones, and weight. The subjects in the low-carbohydrate group were provided with a copy of “Dr. Atkins’ New Diet Revolution” and the conventional high-carbohydrate group received “The LEARN Program for Weight Management.”
The research showed that results of the low carb diet showed short-term benefits. Long-term advantages were inconclusive. Patients following the low carbohydrate diet experienced greater weight loss at 3 months and 6 months. However, the results at 12 months were not significant. Ultimately, there was no relationship between ketosis and weight loss. The authors concluded that although HDL levels increased and triglyceride levels decreases for much of the time period, a low-carb diet was not associated with decreased LDL cholesterol. Notable issues with the study include a high drop-out rate of 41%. Additionally, there was no food journal or diary maintained by participants to scrutinize adherence to their specified diet. Ketosis was not always present in the low-carbohydrate group, which conveyed that a true keto diet was not followed. With respect to cardiovascular risk, the study was inconclusive on the benefits of the Atkins diet and the overall safety of the low-carbohydrate diet.
Another study used 22 participants (n = 22) classified as overweight or obese with a BMI over 25kg/m2 [6]. The subjects had not been diagnosed with any chronic disease and did not use drug prescriptions. This study consisted of a low-carbohydrate diet, enriched with proteins. Participants were provided with specific instructions regarding their diet for 6 weeks. They consumed one packet of Myopenta daily. Whey proteins were used because other studies showed that whey increases muscle growth and decreases blood pressure and inflammation. The subjects were followed by a dietician weekly. Moderate exercise was encouraged, but not structured. Lab samples were drawn following a nightly fast, including plasma glucose, Vitamin D, TSH, and plasma lipids. Body composition was evaluated and ultrasound measurement of the carotid artery was performed. The authors report significant results noted with the low-carbohydrate diet, which specifically consisted of decreased body weight, waist circumference, fat mass, diastolic blood pressure, triglycerides, total cholesterol, pre-albumin, insulin, FT3, and c-IMT. The study conclusion indicated that a low-carb diet would be beneficial in order to start losing weight.
However, the limitations of the study are worth considering. As identified by the authors, the research lacked a formal control group. There was no control of participants not taking the Myopenta and no other diet was compared. The number of participants was quite small. The authors also relayed that the limited number of subjects did not allow for detailed information to be extrapolated, such as BMI, gender, and physical activity. There was weekly monitoring of food intake by the dietician, but no discussion of a food journal or diary, or whether there were issues with adherence to the diet. There was also no long-term following of the subjects more than the six-week length. Although the preliminary results showed some promise, the study design contained serious flaws.
A third study (n = 132) included subjects with a BMI of at least 35 to enroll [7]. The participants were considered severely obese with a mean BMI of 43. They were noted to have a high rate of chronic disease including diabetes (39%) and metabolic syndrome (43%). The subjects were randomly assigned to a carbohydrate-restricted or calorie- and fat-restricted diet. Each group received education led by a nutrition expert. For the first four weeks, the participants received 2 hours of education and subsequently one-hour monthly sessions for the next five months. The low-carbohydrate group was restricted to ≤ 30g of carbohydrate daily. For the low-fat group, subjects were asked to follow guidelines by the National Heart, Lung, and Blood Institute on obesity management guidelines with calorie restriction to create a deficit of 500 calories per day with ≤30% from fat. The participants received a diet handout, instructions on nutrition labels, sample menus, recipes, and education on counting carbohydrates and calories. No specific exercise was recommended. The conclusion of the study showed that there was more weight loss among the low-carbohydrate diet. The author proposed that the weight loss could be due to the overall caloric intake, simplicity of the diet or improved compliance. The participants experienced lower triglyceride levels, diabetics showed greater glycemic control, and non-diabetics showed better insulin sensitivity.
However, this study, too, had noteworthy limitations. The research experienced a high attrition rate of 79 of 132 subjects, which is a dropout rate of approximately 40%. The authors stated that the weight loss may have been associated with decreased triglyceride level and increased insulin sensitivity associated with the low-carbohydrate group. However, other factors were the type of carbohydrates consumed, proportion of complex carbohydrates, or the quantity of fiber. The control group had followed the Obesity Management Guidelines of the National Heart, Lung, and Blood Institute. A low-calorie diet was recommended, but the type of nutrition was not discussed. Again, there was no food journal or diary kept by the subjects. The authors did not reveal how or if the adherence to the diet was monitored. The study was fairly short, lasting 6 months. Because there was no long-term data reviewed, the authors noted that the diet cannot be endorsed without knowing long-term cardiovascular outcome.
As a follow up, a separate study was published investigating the effects of these subjects after one year [8]. This time, there were 87 participants of the 132 original identified subjects. After one year, the weight change differences were not significant between the two groups. The authors also found that subjects on the low-carbohydrate diet experienced more of a decrease of triglyceride levels and improved HgA1c levels. The conclusion was that the low-carbohydrate diet was better after one year in terms of atherogenic dyslipidemia, specifically triglyceride and HDL cholesterol, as well as glycemic control for patients with diabetes. However, there was not a significant difference in weight loss. The overall effect upon cardiovascular health and diabetes were not known.
The limitations continued in the second study with a high attrition rate (34%), small sample size, and poor adherence of the diet. While data was not collected for all participants at the 6- and 12-month marks, weight could be collected retrospectively through medical records. The authors accounted for the missing data through sensitivity analysis. Adverse reactions were also reported. The low-carbohydrate group showed an increase in blood urea nitrogen, which is related to kidney function. Within the same group, one person was hospitalized for chest pain, which was reported not cardiac-related. Two people died. The authors related that there is likelihood that the low-carbohydrate diet is not sustainable and that the diet may be optimal for metabolic effects on obese people, who overconsume carbohydrates. Finally, more research is needed on the effect upon cardiovascular and diabetes outcomes.
In a commentary proceeding the two studies, Dean Ornish, a well-known physician who uses preventive lifestyle medicine, raised several points. Although the low-carbohydrate diet appeared to have more beneficial results, neither diet was able to achieve significant weight loss or lower LDL levels. Other studies show that dietary cholesterol and total fat contributes to atherosclerosis. People on the conventional diet described in the studies used refined carbohydrate. However, whole food carbohydrate was not discussed. Ornish commented:
The debate should not be "low carbohydrate” versus "low fat.” Patients have a spectrum of dietary choices. To the degree they reduce their intake of refined carbohydrates and excessive fats and increase their intake of unrefined carbohydrates (fruits, vegetables, whole grains, legumes)… they may feel better, lose weight, and gain health.
In the final study, 53 adult female participants were described as having a BMI between 30 – 35, and stable body weight for six months [9]. Measurements were taken at the 3- and 6-month mark after beginning the diet. This included fasting blood and body fat through DEXA scans. The subjects were divided into two groups. One group was instructed to eat a low carbohydrate diet of 20g of carbohydrate per day, then after two weeks increased to 40 to 60 g/day if urinary ketones showed ketosis. The other group was asked to consume a calorie-restricted and moderately low-fat diet with 55% carbohydrate, 15% protein, and 30% fat. To promote compliance, dieticians provided an intervention at three months and biweekly group meetings comprising cooking tips, behavior modification, stress management, and prevention of relapse. Additionally, participants met with an assigned dietician on specified weeks, submitted a three-day food journal, and were weighed. Blood pressure and urinary ketones were also monitored.
The results showed that in addition to lower carbohydrates, the low-carbohydrate group also consumed less vitamin C and fiber at three months and again at six months. The low-fat group consumed less protein, cholesterol, total fat, saturated fat, monosaturated fat, and polyunsaturated fat. Body weight, fat mass, and lean body mass decreased in both groups, greater overall in the low-carbohydrate group. No differences occurred in blood pressure and remained stable for both groups. The authors concluded that people who consume a low-carbohydrate diet can avoid negative effects of food through restriction of calorie intake. Throughout the study, normal levels were seen relating to blood pressure, plasma lipids, glucose, and insulin in this group.
Like the previous studies, several limitations were noted. The length of the research was very short, of six months. The dropout rate was 21% with 42 of 53 women completing the study. The authors proposed important shortcomings. The study only consisted of healthy adults and none with cardiovascular risk factors. Furthermore, the findings only represent one small study, and sustained safety and efficacy of the low-carbohydrate diet was not determined. Additionally, long-term weight loss and effect on cardiovascular health was not discovered. The low intake of calcium and fiber in the low-carbohydrate group may lead to a negative ramification, as well as perpetual ketosis. According to the authors, enduring ketosis may be associated with heart issues. In general, this study was better designed than the preceding ones discussed above. There was a stricter follow up to dietary adherence, including the 3-day food journal. When subjects dropped out, the reasons were disclosed, such as dislike of diet.
Summary of Research Findings
Overall, these five studies appeared to have a short amount of time allotted to the research with a maximum of one year, a high attrition rate, and a mostly low adherence rate to the specified diet. None of these studies were conclusive on long-term effects, especially with respect to cardiovascular effects. None of the studies included or mentioned a whole food plant-based diet as a control.
Furthermore, subjective findings would be helpful in examining meaningful diet changes. While lab values may have decreased with certain criteria, the participants may have felt poorly. Subjective findings, in addition to barriers that the subjects perceived, would give additional breadth of knowledge regarding effectiveness. Likewise, discerning if subjects dropped out due to negative effects of a low-carbohydrate diet would have contributed to the research implications.
Although consent was obtained in these studies, the negative ramifications of a low-carbohydrate diet were not discussed very much. The authors did not disclose in the published research about potential hazards for this type of diet, and stated that safety of the diet was largely unknown. The exceptions were in the studies Brehm and colleagues [9] and Foster and coauthors [5], which indicated that enduring ketosis could contribute to cardiac issues.
Other uses for the ketogenic diet
For the general population, the long-term outcome of the ketogenic diet is inconclusive. However, the diet may be beneficial in some cases. For example, it has some success in treating seizure disorders like epilepsy among children [10]. While the brain largely uses glucose for energy and functioning under normal conditions, it will metabolize ketones when glucose is not available. The history of a ketogenic diet in epilepsy is longstanding, which historically has been treated with fasting or other dietary guidelines for millennia. In 1921 investigators noted that acetone and beta-hydroxybutyric were present following a subject exposed to either starvation or a diet low in carbohydrates. The scientists focused on a ketogenic diet because the method would likely be as effective as fasting and could be maintained for a longer time period. Children showed benefit and one publication noted that of 1000 children, 52% gained complete control of seizures and another 27% experienced a greatly improved condition [11]. The diet offers an alternative to expensive seizure medications, which have toxic side effects and can be ineffective towards refractory seizures. Yet, using this treatment should be done under close physician supervision as it can have adverse effects and adherence is difficult [4].
Another use for a restricted ketogenic diet is in some cancers, such as brain cancer [12]. Current standard of care for brain cancer includes surgical resection, chemotherapy, and radiation therapy. Patients also frequently receive a drug called dexamethasone, which is a corticosteroid and raises blood glucose levels. Emerging research discusses that glucose and glutamine can actually be the fuel for growth of malignant cells. Glutamine is a type of amino acid that is related to the neurotransmitter glutamate, a neurotransmitter in which transporters are present on glial cells. Disruption of the glutamine-glutamate pathway provides glioblastoma multiforte, the most malignant form of brain cancer, the glutamine it needs for fuel. Conventional forms of treatment can lead to neurotoxicity and cause increased glutamine.
The presence of these molecules of both glucose and glutamine leads to the acceleration of tumor growth, and also causes a high probability of recurrence and reduced survival. Studies have shown that the ketogenic diet can reduce glucose and possibly lower brain glutamine levels. In this way, tumors may be decreased in size and inflammation, as well as the produce new blood vessels. While conventional treatment has a very low survival rate, the ketogenic diet may be a worthwhile application, provided that the patient maintains compliance and motivation.
Conclusion
Ketogenic diets may offer benefits to patients with specific conditions, such as seizure disorder or brain cancer. However, eating this type of diet is largely not recommended for most people. Carbohydrates are the main source of fuel for the body, evident in fruits, vegetables, and whole grains. Additionally, minerals, phytochemicals, and fiber are found in carbohydrates and needed by the body. Diets lacking in fiber have a direct impact to the gut microbial flora. Consuming a high-fat diet is linked with many chronic diseases, including cardiovascular disease, Alzheimer’s, cancer, diabetes, and chronic kidney disease. On a high-fat diet, LDL cholesterol can increase significantly. Low-carbohydrate diets are not shown to be more effective at weight loss than calorie-restricted or low-fat diets [4]. A carbohydrate-rich whole food plant-based diet has demonstrated significant improvements in health.
References:
1. Centers for Disease Control and Prevention. (2023). Obesity and overweight. https://www.cdc.gov/nchs/fastats/obesity-overweight.htm
2. World Health Organization. (2021). Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
3. Nordli, D. R., & De Vivo, D. C. (1997). The ketogenic diet revisited: Back to the future. Epilepsia, 38(7), 743-749. https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1528-1157.1997.tb01460.x
4. Crosby, L., Davis, B., Joshi, S., Jardine, M., Paul, J., Neola, M., & Barnard, N. D. (2021). Ketogenic diets and chronic disease: Weighing the benefits against the risks. Frontiers in Nutrition, 8, 702802.
5. Foster, G. D., Wyatt, H. R., Hill, J. O., McGuckin, B. G., Brill, C., Mohammed, B. S., Szapary, P. O., Rader, D. J., Edman, J. S., Klein, S. (2003). A randomized trial of a low-carbohydrate diet for obesity. New England Journal of Medicine, 348, 2082-2090. https://doi.org/10.1056/NEJMoa022207
6. De Pergola, G., Zupo, R., Lampignano, L., Paradiso, S., Murro, I., Cecere, A., Bartolomeo, N., Ciccone, M. M., Giannelli, G., & Triggiani, V. (2020). Effects of a low carb diet and whey proteins on anthropometric, hematochemical, and cardiovascular parameters in subjects with obesity. Endocrine, Metabolic & Immune Disorders Drug Targets, 20(10), 1719–1725. https://doi.org/10.2174/1871530320666200610143724
7. Samaha, F. F., Iqbal, N., Seshadri, P., Chicano, K. L., Daily, D. A., McGrory, J., ... & Stern, L. (2003). A low-carbohydrate as compared with a low-fat diet in severe obesity. New England Journal of Medicine, 348(21), 2074-2081. https://doi.org/10.1056/NEJMoa022637
8. Stern, L., Iqbal, N., Seshadri, P., Chicano, K. L., Daily, D. A., McGrory, J., ... & Samaha, F. F. (2004). The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Annals of Internal Medicine, 140(10), 778-785. https://doi.org/10.7326/0003-4819-140-10-200405180-00007
9. Brehm, B. J., Seeley, R. J., Daniels, S. R., D’Alessio, D. A. (2003). A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. The Journal of Clinical Endocrinology & Metabolism, 88(4), 1617 – 1623. https://doi.org/10.1210/jc.2002-021480
10. Martinez, C. C., Pyzik, P. L., & Kossoff, E. H. (2007). Discontinuing the ketogenic diet in seizure‐free children: Recurrence and risk factors. Epilepsia, 48(1), 187-190. https://doi.org/10.1111/j.1528-1167.2006.00911.x
11. Wheless, J. W. (2008). History of the ketogenic diet. Epilepsia, 49, 3-5. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1528-1167.2008.01821.x
12. Seyfried, T. N., Marsh, J., Shelton, L. M., Huysentruyt, L. C., & Mukherjee, P. (2012). Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer?. Epilepsy research, 100(3), 310-326. https://doi.org/10.1016/j.eplepsyres.2011.06.017