Copyright © 2004, Pulsus Group Inc. All rights reserved

Clinical Cardiology

Long-term effects of a ketogenic diet in obese patients

Hussein M Dashti, MD PhD FICS FACS,¹ Thazhumpal C Mathew, MSc PhD FRCPath,⁴ Talib Hussein, MB ChB,⁵ Sami K Asfar, MB ChB MD FRCSEd FACS,¹ Abdulla Behbahani, MB ChB FRCS FACSI PhD FICS FACS,¹ Mousa A Khoursheed, MB ChB FRCS FICS,¹ Hilal M Al-Sayer, MD PhD FICS FACS,¹ Yousef Y Bo-Abbas, MD FRCPC,² and Naji S Al-Zaid, BSc PhD³

¹Departments of Surgery

²Medicine and

³Physiology, Faculty of Medicine, and

⁴Faculty of Allied Health Sciences, Kuwait University, Safat;

⁵Ministry of Health, Safat, Kuwait

Correspondence: Dr Naji Al-Zaid, Department of Physiology, Faculty of Medicine, PO Box 24923, 13110, Safat, Kuwait. Telephone 965-531-9593, fax 965-531-9597, e-mail alzaidnajeee@hotmail.com

BACKGROUND:

OBJECTIVE:

In the present study, 83 obese patients (39 men and 44 women) with a body mass index greater than 35 kg/m², and high glucose and cholesterol levels were selected. The body weight, body mass index, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, fasting blood sugar, urea and creatinine levels were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored after eight, 16 and 24 weeks of treatment.

Keywords: Diet, Ketosis, Obesity

RESULTS

The mean initial weight of the subjects was 101.03±2.33 kg. The weight decreased significantly during all stages of the treatment period. The body weights at the eighth, 16th and 24th week were 91.10±2.76 kg, 89.39±3.4 kg and 86.67±3.70 kg, respectively (Figure 1). Similar to the loss in body weight, a significant decrease was observed in the BMI of the patients following the administration of the ketogenic diet. The initial BMI, and the BMI after the eighth, 16th and 24th week were 37.77±0.79 kg/m², 33.90±0.83 kg/m², 33.24±1.00 kg/m² and 32.06±1.13 kg/m², respectively

(Figure 2).

The level of total cholesterol showed a significant decrease from week 1 to week 24 (Figure 3). The level of HDL cholesterol significantly increased (Figure 4), whereas LDL cholesterol levels significantly decreased with treatment (Figure 5). The level of triglycerides decreased significantly after 24 weeks of treatment. The initial level of triglycerides was 2.75±0.23 mmol/L, whereas at week 24, the level decreased to 1.09±0.08 mmol/L (Figure 6). The level of blood glucose significantly decreased at week 24. The initial blood glucose level and its level at the eighth, 16th and 24th week were 7.26±0.38 mmol/L, 5.86±0.27 mmol/L, 5.56±0.19 mmol/L and 5.62±0.18 mmol/L, respectively

(Figure 7). The changes in the levels of urea (Figure 8) and creatinine (Figure 9) were not statistically significant.

DISCUSSION

Until recently, ketosis was viewed with apprehension in the medical world; however, current advances in nutritional research have discounted this apprehension and increased public awareness about its favourable effects. In humans, ketone bodies are the only additional source of brain energy after glucose (23,24). Thus, the use of ketone bodies by the brain could be a significant evolutionary development that occurred in parallel with brain development in humans. Hepatic generation of ketone bodies during fasting is essential to provide an alternate fuel to glucose. This is necessary to spare the destruction of muscle from glucose synthesis.

A ketogenic diet is clinically and experimentally effective in antiepileptic and antiobesity treatments; however, the molecular mechanisms of its action remain to be elucidated. In some cases, a ketogenic diet is far better than modern anticonvulsants (25). Recently, it has been shown that a ketogenic diet is a safe potential alternative to other existing therapies for infantile spasms (27). It was further shown that a ketogenic diet could act as a mood stabilizer in bipolar illness (28). Beneficial changes in the brain energy profile have been observed in subjects who are on a ketogenic diet (28). This is a significant observation because cerebral hypometabolism is a characteristic feature of those who suffer from depression or mania (28). It has also been found that a ketogenic diet affects signal transduction in neurons by inducing changes in the basal status of protein phosphorylation (29). In another study (30), it was shown that a ketogenic diet induced gene expression in the brain. These studies provide evidence to explain the actions of a ketogenic diet in the brain.

One of the mechanisms of a ketogenic diet in epilepsy may be related to increased availability of beta-hydroxybutyrate, a ketone body readily transported through the blood-brain barrier. In support of this hypothesis, it was found that a ketogenic diet was the treatment of choice for glucose transporter protein syndrome and pyruvate dehydrogenase deficiency, which are both associated with cerebral energy failure and seizures (26).

One argument against the consumption of a high fat diet is that it causes obesity. The major concern in this regard is whether a high percentage of dietary fat promotes weight gain more than a low percentage of fat intake. Because fat has a higher caloric density than carbohydrate, it is thought that the consumption of a high fat diet will be accompanied by a higher energy intake (31). On the contrary, recent studies from our laboratory (12) and many other laboratories (24,32–34) have observed that a ketogenic diet can be used as a therapy for weight reduction in obese patients.

It has been found that a sugary diet is the root cause of various chronic diseases of the body. A recent study (35) showed that sugar can accelerate aging. Several recent studies (36,37) have pointed to the fact that a diet with a high glycemic load is independently associated with the development of cardiovascular diseases, type II diabetes and certain forms of cancer. Glycemic load refers to a diet of different foods that have a high glycemic index. Glycemic index is a measure of the elevation of glucose levels following the ingestion of a carbohydrate. The classification of a carbohydrate based on its glycemic index provided a better predictor of risk for coronary artery diseases than the traditional method of classification of carbohydrate into simple or complex forms (38). In other studies (38–46), it was shown that the risk of dietary glycemic load from refined carbohydrates was independent of other known risk factors for coronary diseases.

It is now evident that high carbohydrate diets increase fasting plasma triglyceride concentrations (47–51) and decrease HDL cholesterol concentrations (52–55). These changes are associated with enhanced atherogenesis (55). However, it has been shown that short-term ketogenic diets improve the lipid disorders that are characteristic of atherogenic dyslipidemia (56). It has also been found that sugary drinks decreased blood levels of vitamin E, thus reducing the amount of antioxidants in the body. It has been proven, beyond a doubt, that disrupting the oxidant-antioxidant status of the cell will lead to various diseases of the body (57).

The relation between a high fat diet and cancer is not conclusive. Recent epidemiological studies (17,58–60) could not explain a specific causal relationship between dietary fat and cancer. It has been found that altered energy metabolism and substrate requirements of tumour cells provide a target for selective antineoplastic therapy. The supply of substrates for tumour energy metabolism can be reduced by dietary manipulation (eg, ketogenic diet) or by pharmacological means at the cellular level (eg, inhibitors of glycolysis or oxidative phosphorylation). Both of these techniques are nontoxic methods for controlling tumour growth in vivo (61). Sugar consumption is positively associated with cancer in humans and test animals (58–61). This observation is quite logical because tumours are known to be enormous sugar absorbers. It has also been found that the risk of breast cancer decreases with increases in total fat intake (16). Further studies on the role of a ketogenic diet in antineoplastic therapy are in progress in our laboratory.

A link between low fat diets and osteoporosis has been suggested. Very low fat diets are considered to be low in calcium content. Women on low fat diets excrete most of the calcium they consume; therefore, they are more prone to osteoporosis. However, a high fat diet can rectify this situation (62).

In the present study, a control population on a low fat diet was not included due to the difficulties in recruiting subjects for a control group. However, several studies (63,64) with appropriate control groups that compared the effect of a low fat diet with a low carbohydrate ketogenic diet have recently been published. In this regard, these two recent studies are comparable with the present study. Brehm et al (23) showed that obese women on a low carbohydrate ketogenic diet lost 8.5 kg over six months compared with 4.2 kg lost by those in the low fat diet group (P<0.001). Twenty-two subjects from the low carbohydrate ketogenic diet and 20 subjects from the low fat diet completed the study, with both groups reducing their energy intake by approximately 450 kcal from the baseline level. In another study performed in 132 severely obese subjects for six months (24), there was greater weight loss in the low carbohydrate ketogenic diet group than in the low fat diet group (5.8 kg versus 1.9 kg, P=0.002). Both of these studies support the findings presented in the present paper.

REFERENCES