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The KD, a diet low in carbohydrates and high in fat and protein, has been shown to effectively reverse obesity, metabolic syndrome, and type 2 diabetes. It also has therapeutic potential for treating other chronic diseases. By identifying genetic and dynamic markers of KD response, we can pinpoint those who are most likely to benefit from the diet and those who may be at risk for negative health effects.
The Genetic Factor That Poses a Risk with the Ketogenic Diet:
The APOE2 gene is most compatible with a diet that is high in fat and low in carbohydrates, with a preference for saturated fats.
APOE3 is appropriate for both.
For individuals with APOE4, a diet high in monounsaturated fats and low in carbohydrates is recommended, while saturated fats should be avoided.
According to research, individuals who carry the APOE4 gene are particularly susceptible to the negative effects of high cholesterol. They can benefit greatly from a diet low in saturated fats and high in monounsaturated fats and low carbohydrates. Conversely, those who carry the APOE2 gene are better suited to a high-fat, low-carbohydrate diet, regardless of the amount of saturated fats consumed.
PDCD is caused by genetic mutations in PDHA1 (most common), PDHX, PDHB, DLAT, PDP1, and DLD, resulting in the inability to properly utilize pyruvate from carbohydrates and an increase in lactate. The introduction of a ketogenic diet allows cells to derive energy from fatty acids instead. On the other hand, GLUT1 DS is caused by genetic mutations in SLC2A1, which encodes for the protein GLUT1 responsible for transporting glucose into the brain. The ketogenic diet is used as an alternative fuel source, providing the brain with ketones.
In a study of 86 adults, consisting of 53 overweight men and 33 women who were either normoweight or overweight, it was discovered that certain SNPs in genes responsible for metabolic enzymes such as gastric lipase (LIPF, rs814628-G), hepatic glycogen synthase (GYS2, rs2306179-C), cholesteryl ester transfer protein (rs5883-T), and galanin (rs694066-G) were significantly linked to a greater weight loss in response to a KD (8%-13% carbohydrates, 60%-63% fat, and 28%-30% protein) over a period of 4-12 weeks.
The response to KD resulted in greater weight loss for individuals with 5 genetic variants: rs814628-G in gastric lipase (LIPF), rs2306179-C in hepatic glycogen synthase (GYS2), rs5883-T in cholesteryl ester transfer protein (CETP), and rs694066-G in galanin (GAL).
The angiotensin II receptor type 2 (AGTR2, rs5950584-G) was linked to a more significant decrease in body fat percentage when following a KD diet, according to one genetic variation study.
In patients with Alzheimer's disease, the genetic variant APOE, rs429358-T was linked to a more significant cognitive enhancement when treated with MCT-based agents.
The chromodomain Y ligand 1 (CDYL1, rs12204701-G) genetic variant was linked to a more significant reduction in seizures among individuals with epilepsy.
Follow the link of the selected polymorphism to read a brief description of how the selected polymorphism affects Keto diet and lchf and see a list of existing studies.
SNP polymorphisms related to the topic Keto diet and lchf:
| rs3916 | |
| rs4994 | A beta-3-adrenergic receptor mutation is associated with visceral obesity but lowers serum triglyceride levels. Carriers of the G allele necessarily need strength training to lose weight and keep the body in good shape. |
| rs5883 | CETP regulates reverse cholesterol transport, a process by which excess cholesterol is removed from peripheral tissues and returned to the liver. CETP may mediate the triglyceride-lowering and LDL and HDL remodelling effects observed with low-carbohydrate diets. |
| rs274555 | |
| rs597539 | |
| rs694066 | |
| rs814628 | A polymorphism in the LIPF gene contributes to reduced breakdown of fat in the stomach and promotes more effective weight loss on high-fat diets. |
| rs1440581 | Association of the rs1440581 variant of the PPM1K gene with improved insulin sensitivity in people who followed a high-fat diet. |
| rs1522813 | Positive feedback and effective weight loss on high-carbohydrate, high-fat restricted diets. |
| rs1799883 | This genotype is associated with increased sensitivity to both saturated fat and refined carbohydrates. Thus, allele A impairs the effectiveness of both low-carbohydrate and low-fat diets. |
| rs1799958 | |
| rs1801282 | Peroxisome proliferator-activated receptor gamma gene variation on the progression of type 2 diabetes and obesity. Also higher risk of cardiovascular disease with a diet high in saturated fat. |
| rs2286963 | |
| rs2306179 | gene is responsible for hepatic glycogen synthase, which catalyses the formation of glycogen from glucose in the liver. According to the study carriers of the minor allele C lost more weight than homozygotes for the major allele T in response to a keto diet (8-13% carbohydrate, 60-63% fat and 28-30% protein) over a period of 4-12 years. This suggests that the liver glycogen response to carbohydrate restriction may influence the weight loss response to the keto diet. |
| rs2924679 | |
| rs3764261 | People with the CETP rs3764261 CC genotype may achieve a greater effect in raising HDL cholesterol and lowering triglyceride levels by choosing a low-carbohydrate, high-fat weight loss diet instead of a low-fat diet. |
| rs5950584 | In the study, the minor G allele was associated with a greater reduction in body fat percentage in response to the keto diet, with ~12% of total energy derived from carbohydrates. Given that the AGTR2 gene is X-linked, its effect on fat loss in BC may be more prevalent and/or stronger in men than in women. |
| rs7938117 | |
| rs9943291 | |
| rs10060615 | |
| rs11161521 | |
| rs12204701 | The A allele of the CDY1L gene rs12204701 contributes to seizure reduction efficacy of more than 50% in patients with drug-resistant epilepsy in response to a keto diet. |