We have discussed Ketosis through our various blogs & webinar conducted on 15th December’2019. In brief, keto diet follows a high fat (70% to 80%), low carbohydrate (5% to 10%) & moderate protein intake (15% to 30%). Such a diet allows your body to produce ketones out of fat which is used as fuel instead of glucose (derived from carbohydrates).
Intermittent fasting which taps into Ketosis for a limited period of time by restricting feeding times to 8 to 10 hours window is said to have numerous benefits including increased good gut bacteria, decreasing risk of cancer, increasing fat burning & improving fasting glucose & insulin levels.
Fasting & entering Ketosis is a form of hormetic stress which can have beneficial responses in an individual. However for some people Ketosis & intermittent fasting can be stressful. This has been observed in people facing digestive issues or feeling nauseous after consuming too much fat whose lipid biomarkers go off the chart, have a sensitive thyroid gland & face hypoglycemia when going too long between meals. What can be the reason behind this? Clearly, such forms of diet do not go well with their genetic composition as far as optimal health is concerned.
Given that such forms of diet have become famous, it is vital to understand why these diets may not work for everyone. There is variation in response towards fasting & high fat diet which is due to genetic differences in metabolism which can lead to positive or adverse impact on your health.
Arctic population has an adaptation of a specific diet & long standing in one specific environment. The diet followed by these people consisted of 30% protein, low carbohydrates & high in omega-3 & omega-6 fatty acids. This is the wrong assumption of the Arctic population that they are in a state of Ketosis. While it is true that they are following a low carbohydrate & high fat diet in certain parts of the year due to their genetic differences & interplay between genes & environment, their body creates glucose from high intake of protein.
Inuit or those living in the arctic have deleted variants in FADS1 & FADS2 (protein coding genes) that essentially means it creates inability to convert plant Omega-3 fatty acids to EPA & DHA, another reason why Inuit consume animal based Omega-3 in high quantities.
CPT1A gene, found in liver & kidney, is responsible for Ketosis & is a key regulator for importing long chain fatty acids to mitochondria to help maintain energy when carbohydrate is low.
People living in regions such as Canada & Arctic have homozygous genotypes in the CPT1A gene. Some people have the “ Arctic Mutation” variant in this gene. This mutation results in 20% less enzyme activity causing low levels of Ketones & low blood sugar resulting in lack of Ketogenesis & promotion of hypoglycemia in response to fasting. Why does this happen?
For people living in cold areas & near to mountains, CPT1A mutation increases heat in the body by directing free fatty acids away from liver cells to brown fat. It creates a greater capacity of gluconeogenesis & improved ability to remove excess ammonia from a high protein diet.
Omega-3 fatty acids increase mitochondrial fatty acid oxidation by stimulating the activity of CPT1A. The effects of the mutations in CPT1A occur when the traditional diet changes to a high-carbohydrate diet or environmental stressors such as fasting (especially during strenuous exercise).
PPAR alpha gene plays a major role in fatty acid metabolism, apolipoproteins, HDL, LDL & ketone body production during fasting. Like the CPT1A gene, variants in the PPAR alpha gene may cause low Ketone production during fasting. It is sensitive to saturated fat intake & stimulated by Omega-3 fatty acids intake (only nuts & seeds). Besides, PPAR alpha is also stimulated by wild salmon, crab, shrimp, blueberries, cranberries, zinc (high in seafood) & tomatoes. Coconut oil (natural saturated fat) does not negatively impact PPAR alpha gene like other forms of saturated fats. Variants in this gene point towards coastal culture that is adaptable to high omega-3 intake.
Many people with variants in this gene have blood sugar levels that drop quickly, have issues with saturated fat intake & do well while consistently have 3 meals & regular snacks throughout the day. This gene would tell you if it’s better for you to have 3 meals a day, skipping breakfast or eat three meals with snacks in between.
Fasting & ketosis may create too much stress with people having above-mentioned variants in PPAR alpha genes. It would be at best to shift to monounsaturated & polyunsaturated fat in their diet, lower fasting times & consistent intake of foods that stimulate PPAR alpha gene. This is the reason we always endorse that fitness is never about one-size fits all and multiple variations may be required for every diet for each individual.
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