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PPARA

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Under normal circumstances, the body’s preferred source of energy is glucose derived from carbohydrate. By contrast, a ketogenic diet relies on burning fat for energy, producing ketone bodies and thus entering a state of ketosis.
When a state of dietary ketosis is achieved, blood ketone test results will usually fall between 1.5 and 3.0 mmol/L. This equates to 150-300 mg/dL. Dr. Veech at Harvard was one of the first scientists to show how ketones confer a protective effect in the body. However, emerging research teaches us that not everyone can achieve a state of nutritional ketosis.
Some reach the 1.5 mmol/L threshold with ease while others struggle. Why?
PPARA variants impact fat metabolism and the body’s response to different fatty acids. (R)(R)
The PPARA gene is a key player in this process which functions to activate fat metabolism in the liver, producing the sought after elevation in ketone bodies. As such, a reduction in PPARA activity can be associated with several effects, namely increased circulating triglycerides, total cholesterol, LDL and apoB count, and an overall poorer response to saturated fat in the diet.
But most importantly, reduced PPARA activity is associated with an increased difficulty in entering ketosis. (R)(R) After all, if you cannot enter a state of ketosis, you cannot achieve the benefits of a ketogenic diet, and thus may want to consider a different approach.
The “G” allele of the SNP rs1800206 (also known as L162V) in the PPARA gene is associated with reduced PPARA activity and an increased difficulty entering ketosis.

L162V

Science Grade
A+
Heart Health
rsID Number Major Allele Minor Allele
rs1800206 c g

Risk Description

The “G” allele of the SNP rs1800206 (also known as L162V) in the PPARA gene is associated with reduced PPARA activity and an increased difficulty of entering ketosis.

Direct Nutrients:*

Ingredient Active Ingredient Effect
Polyunsaturated fatty acids

A large study found that carriers of the risk G allele benefitted from consuming larger amounts of polyunsaturated fatty acids (PUFA). Carriers of the G allele’s triglyceride and apoC-III levels went up on a low-PUFA diet. By contrast, when the PUFA intake increased, they had lower triglyceride and apoC-III levels. The study authors pointed made sure to note that the PUFA response was dose dependent.  The more PUFA G allele carriers ate, the more their triglycerides and apoC-III levels dropped. (R) (R)

Nutritional Contraindications:*

Ingredient Active Ingredient Effect
Saturated fat

Diets high in saturated fat are contraindicated for carriers of the G allele for rs1800206. Studies show these individuals will have a poor LDL response on high saturated fat diets. (R)

Discuss this information with your doctor before taking any course of action.

Dr. Aaron Gardner, BSc, MRes, PhD

Dr. Aaron Gardner, BSc, MRes, PhD is a life-scientist with a strong background in genetics and medical research, and the developing fields of personalized medicine and nutrition. Read his full bio here.
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