Effect of a Ketogenic Diet on Body Weight and Lipid Profile

This review article aimed to study the effects of a ketogenic diet on obesity-related measures, and lipid profiles. Total 22 articles were included in the review. Anthropometric measures included in the review were total body mass (Wt), fat mass (FM), body mass index (BMI), and waist circumference (WC). Lipid profile included in this review was serum cholesterol level, serum HDL, serum LDL, and serum triglycerides (TAG). The shortest intervention in these studies lasted for 4 days, and the longest intervention lasted for 12 months. There was a significant Wt loss in all studies. Significant reduction in BMI, FM, and WC was also observed in many studies. In most studies, variable effects on lipid profile were observed. Serum TC level fell in 10 studies and serum TAG levels decreased in 13 studies, but this reduction was statistically insignificant in most studies. Serum LDL level fell in 10 studies and increased in 3 studies, and serum HDL levels fell in 7 studies and increased in 6 studies, but these changes were also not statistically significant in most studies. This review article found beneficial effects of ketogenic diet weight loss and lipid profile, but the studies in this review included dietary intervention of a period≤12 months. Studies for extended periods (at least ≥2 years) should be done to observe long-term effects of a ketogenic diet.

This review article was aimed at studying outcomes of KD and VLCKD on obesity-related measures, and on lipid profile. It also discussed the effects of KD on certain obesity-related diseases.

MATERIALS AND METHODS: Review of Literature
A systematic literature search Google scholar was performed to identify various studies published since 2017. Only those studies were included which were done on "human subjects", with overweight or obesity. Studies were included which evaluated the effects of KD and VLCKD on blood sugar control, decrease in fat mass, and lipid profile as main measures. The search terms were composed of a combination of keywords "ketogenic diet or high-fat diet", "weight loss", "lipid profile", "NAFLD", and "Type2 DM". Reference lists of review articles were also screened to identify eligible studies. A total of 49 articles were extracted. Two articles were removed because they were animal studies. Other 17 articles were removed because 12 of them were review articles, one was an editorial, 3 were opinions, and one was a case report. Three more articles were removed because they included only one gender. Further 5 articles were removed because they did not contain desired outcome variables. Hence total 22 articles were selected (Fig. 1).

Outcome measures
Outcome measures included anthropometric measures and biochemical measures. Anthropometric measures included in the review were total body mass (weight= W), fat mass (FM), body mass index (BMI), and waist circumference (WC). Biochemical measures included lipid profile i.e. serum total cholesterol (TC), serum high-density lipoprotein (HDL), and serum low-density lipoprotein (LDL), and serum triglycerides (TAG).

RESULTS:
In our review, the dietary intervention lasted for ≤5 weeks in 10 studies, and for ˃5 weeks in 12 studies. The shortest intervention in these studies lasted for 4 days, and the longest intervention lasted for 12 months (Table 1).

Anthropometric measures
A significant change in Wt was observed in most studies in the review (Table 1). This decline in Wt actually reflected total fat loss, which included loss of visceral fat also. The studies which did not mention body weight, reflected fat loss in form of change in   (Valenzano et al., 2019), and insignificantly in 3 studies, but increased insignificantly in only 2 studies. There was no significant increase in LDL levels in any study.

DISCUSSION:
All studies constituting this review revealed a statistically significant reduction in body fat in terms of weight, fat mass, BMI, and WC. Our review also found correction of lipid profile in most studies. In this review, a variable effect of ketogenic diet was observed on lipid profile. It was expected that a very high-fat diet would lead to derangements in the lipid profile. However, contrary to this expectation, a shift of lipid levels was found towards the healthy side. Serum TC declined in all the studies in which it was measured. Serum LDL and TAG levels increased insignificantly in some studies but fell in majority of the studies, but HDL levels increased in about 50% of these. Our pre-sent review, however, found a decrease in LDL levels in most studies, and even at 12 months of dietary intervention (Perticone et al., 2019).  , 2021). VLCKD also showed achievement of a significant decline in body weight in patients. Results were obtained during the ketogenic phase and weight remained stable over the next two years (Castellana et al., 2020). Our review of literature revealed that there was significant weight loss even in dietary intervention as short as four days.

Effect on serum lipids
In literature, the ketogenic diet showed a rise in HDL levels, along with a rise in amounts of LDL, and verylow-density lipoproteins (VLDL) in blood (Batch et al., 2020). However, in the present review, a variable effect of ketogenic diet was observed on lipid profile. A shift of lipid levels was found towards the healthy side. Serum TC levels declined in all studies, serum LDL and TAG levels increased insignificantly in some studies, but fell in most, and HDL levels increased in about half of them. Review found a decrease in LDL levels in most studies, even at 12 months (Perticone et al., 2019).

Effect on NAFLD
There is a common belief that increasing dietary fat intake leads to fatty liver and prevents fat mass loss. But a normo-caloric high-fat ketogenic diet (HFKD) has been found to inhibit lipogenesis and induce fatty acid oxidation, leading to weight loss and reduced heaptic fat. Conversely, a hypercaloric but proper diet diminishes fat oxidation in liver and increases lipogenesis from carbohydrates, causing NAFLD (Wata-nabe et al., 2020). At very low caloric intake, macro-nutrient disposition is not important in improving liver pathology. It is rather caused by weight loss itself. Whereas at higher calories, the macronutrient ratio seems to become more important. Carbohydrate restriction plays a primary role in the efficacy of KD on NAFLD. Ketosis might affect NAFLD pathogenesis, apart from carbohydrate restriction. Ketone esters reduced glycolysis and increased muscle fat oxidation in the absence of a carbohydrate-restricted diet when administered to athletes . Our review found improvement in lipid profile in most studies, and even a reduction in liver size and statuses in NAFLD patients .

Effect on Type2 DM
Studies found that ketogenic diet could reduce fasting blood glucose and glycosylated hemoglobin, along with improving lipid metabolism and reducing body weight (Yuan et al., 2020). It also improved weight and metabolic parameters in Type2 DM patients (Choi

Effect on cardiovascular diseases
Obesity, hypertension, type2 DM, and NAFLD are all connected, and all are major risk factors for cardiovascular diseases . KD results in decreased bodyweight, TAG, and diastolic blood pressure, and an increment in HDL levels as well (Gupta et al., 2017). All these changes are beneficial for the cardiovascular system.

Effect on polycystic ovary syndrome (PCOS)
PCOS is accompanied by obesity, insulin resistance, LH/FSH ratio, and androgen excess. KD helped treat PCOS by improving body weight, testosterone levels, luteinizing hormone/ follicle-stimulating hormone ratio, and insulin levels (Gupta et al., 2017). KD is not free of adverse events, if not carried out with proper care . If present in large amounts, βhydroxybutyrate, and acetoacetate can result in a decreased blood pH (acidemia). A third ketone, acetone, is neutral, which does not alter blood pH. Acetone can pass through lungs into one's breath, and can make it a ketone biomarker (Blanco et al., 2019).One case report narrated that KD offers short-term weight loss, but it can have potentially harmful side effects like ketoacidosis (Blanco et al., 2019). But this diet can be considered safe for weight loss in diseases like DM, because the ketosis during this diet does not go beyond 7 to 8 mM/L, and hence the possibility of ketoacidosis in these patients is limited (Fig. 2)   KD was found to have positive effects on body weight, BMI, waist circumference, HDL levels, triglyceride levels, blood sugar level, hemoglobin A1c (HbA1c), and insulin levels. However, there was not enough record to support ketogenic diet for long time because most of the studies were of shorter duration, i.e., ranging from 3 months to 3 years. Although most studies mentioned the shift in lipid profile to be favorable, increases were also found in TC and LDL (Batch et al., 2020). Some studies showed that significant differences were found in the first 6 months of intervention, but this statistical significance decreased after one to two years. Meager sample sizes, brief study durations, and absence of control diets decrease validity of these studies (Drabińska et al., 2021). Majority of the studies in the present review had fewer than 50 participants, were of about 3 months duration, and about half of the studies did not have controls. As there is restrained number of strong studies depicting the potential risks of KD, recommendations to support ketogenic diet in patients without comorbidities, should be done by the nutritionist (Batch et al., 2020). VLCKD is a great therapy for people with obesity and especially for those who have already been unsuccessful in losing weight in the past, and/or have an urgency to lose weight. Once the target weight is achieved, it is compulsory to suggest an appropriate healthy lifestyle i.e.
physical activity and a balanced nutritional pattern (Drabińska et al., 2021).

CONCLUSION:
Our literature review found considerable favorable effects of both KD and VLCKD on fat mass and lipid profile, though the studies included in the review included 12 months dietary intervention only. More studies need to be done for extended periods of time (at least ≥2 years) to observe effects of these diets after long duration.

ACKNOWLEDGEMENT:
We thank our colleagues for their moral support and guidance.

CONFLICTS OF INTEREST:
There is no conflict of interest.