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Ketosis – What is it? Can I follow a ketogenic diet? Is it safe? What do my genes say?

Ketosis - What is it? Can I follow a ketogenic diet? Is it safe? What do my genes say?
Ketosis
  1. What is it?
  2. Can I follow a ketogenic diet?
  3. Is it safe?
  4. What do my genes say?
Ketosis has been a buzzword around social media of late, but what is it? 
Ketosis is a natural process that occurs when your body does not have enough glucose for energy, it then burns stored fats resulting in a build-up of ketones in the body. Ketones are produced in your liver when you don’t have enough insulin in your body to turn sugar into energy. Ketones are synthesised from fats you eat and your body’s fat stores. Ketosis can be reached through fasting or following a ketogenic diet.
So what is a ketogenic diet? 
A ketogenic diet is high in fat (70% of total calories) and low in carbohydrates (5-10%). The aim is to achieve ketosis and to sustain this process over a longer period. You are considered to be in nutritional ketosis when your beta-hydroxybutyrate (BHB) levels are between 1-4mmol/L.
Is it healthy to follow a ketogenic diet?
Being in ketosis is safe for most people and it has been shown to provide health benefits including weight loss, optimal blood sugar and insulin levels and improved mental focus.
But it is not safe for everyone. For example, people with type 1 diabetes should avoid being in ketosis because they have a higher risk of developing ketoacidosis, which is potentially life-threatening. Individuals with type 2 diabetes, high blood pressure, liver, heart or kidney disease or during pregnancy should only follow this type of diet under medical supervision.
Saturated fat can be protective and healthful, which is what a well-formulated ketogenic diet is focused around. Reducing saturated fats might not be the right choice for some people. Knowing your genetic blueprint can help establish which food sources are best for you. For the majority of people, ketosis provides a way to balance cholesterol levels, protect your heart, and achieve the ideal body weight. For others, it’s helpful to know in advance if saturated fats can cause a problem, so they can be substituted with other good fats that may work better for their unique genetic make-up.
The Retterstol study showed the variability in response between participants following a high-fat, low-carbohydrate diet. The rise in LDL-C on the high-fat diet varied between 5% in some participants to 107% in others. Clearly showing that one’s genetic make-up plays a big role in how your body will respond to a high-fat diet.  (https://www.sciencedirect.com/science/article/abs/pii/S0021915018314321)
Because of these gene variants, some people do less well on a standard ketogenic diet. Knowing your genetic make-up helps to solve the mystery when you aren’t making progress even when you’re following the diet to the T.
What role do my genes play?
There are several genes that could potential play a role in whether a ketogenic diet will be beneficial or not. The GeneDiet™ test highlights most of these genes and their effect under the Low-fat diet responsiveness section of the report.
PPARG
This gene regulates how easily saturated fats from diet are stored in the body as opposed to burned as fuel.
If you have the CC variant of this gene, you are more likely to store the saturated fats that you eat, so you may have a greater risk of obesity. However, if you have the CT or TT variants, you tend to burn saturated fats more easily.
FTO 
FTO has been termed the “obesity gene”.  The FTO gene impacts on overall body fat depending on how much fat, and especially saturated fat is in the diet.  Fortunately, exercise has a great effect on the expression of this gene.  
Those with the AA variant of this gene tend to preferentially store fats that are eaten, and have a hard time using them as energy. Those with the AT and TT variants burn fats more easily, so can include fats in the diet more freely.
APOC3 
This gene is important in regulating blood triglyceride levels as well as LDL cholesterol, which is the more dangerous type.  Saturated fats in the diet are the modulating factor of how strongly a role this gene plays. 
Those with the CC variant of this gene have a significantly increased risk of atherosclerosis and elevated blood lipid levels when saturated fats are present in the diet. Those with the GG and GC variants do not share this increased risk.
TCF7L2
This gene is strongly linked to the risk of type 2 diabetes because of the potential for decreased insulin secretion and associated weight gain.  
For individuals carrying the TT variant of this gene, eating excess saturated fats can be dangerous since it can elevate the risk for metabolic syndrome. Those with the CC and CT variants do not show the same risk.
APOA2
The APOA2 gene variants determine how your saturated fat intake correlates with your overall cholesterol levels and is also tied to body fat storage.
Those with the CC variant tend to have a higher BMI when saturated fats are included in the diet. The other two variants, CT and TT, do not show this association and can tolerate higher amounts of saturated fats in their diets.
ADRB2
ADRB2 plays a role in energy balance and metabolism.  It’s considered a “thrifty gene” because it can make our bodies more efficient, using as few calories as possible to function.  While efficiency might sound good, in practical terms it means that its easier to eat more calories than you burn, and those extra calories are stored in our fat tissue.  
The GG variant is the most efficient, so those who have this may consider keeping to a lower calorie, and especially lower saturated fat, plan. The AA and AG variants are better at burning excess calories.
ADRB3
This gene does not play a role in how well we add fat to storage.  Instead, it plays a role in how easy or hard it is for our adipose tissue to let go of already stored fats.  
Both the CC and CT variants of this gene tend to hold on to fat harder, and so need less of it in the diet to compensate. The TT variant has an easier time of letting go of fat stores than other variants.
FABP2
This gene affects the way the intestines absorb fatty acids into the bloodstream. About half the population has the AA variant of this gene, and it’s this variant that can absorb fatty acids more quickly than the liver can process. This can lead to elevated LDL cholesterol, so those with this variant may want to reduce saturated fat intake.  
The GG and GA variant can consume saturated fats in the diet without worry.
LPL
This gene helps to modulate whether saturated fats are stored as body fat or burned as fuel, and plays a role in how saturated fats are broken down for energy. 
Those with the GG variant of this gene break down saturated fats and use them for energy easily. The CG and CC variants of this gene, however, have less ability to tolerate saturated fats in the diet, since they can be easily converted into cholesterol.
PPAR alpha
PPAR-alpha increases fat breakdown in the liver. PPAR-alpha is activated under conditions of calorie restriction and is necessary for the process of ketogenesis, a key adaptive response to prolonged fasting. Essentially it increases the uptake of fatty acids. 
Those with the GG variant of this gene have an easier time unlocking the fats already stored in the body when energy is low, so fatty acids can be burned more easily. Those with the CC variant have a harder time accessing stored fats, and those with the CT variant have fat-burning abilities that are between the other two.
VDR
Vitamin D is a fat-soluble vitamin meaning it does not dissolve in water, instead, it is absorbed best when taken with higher-fat foods. Vitamin D helps your body absorb calcium, magnesium, and other minerals. It’s also necessary for maintaining strength and muscle growth, bone density, and healthy testosterone levels, and for supporting cardiovascular and immune system health.
Know the functioning of the VDR genes would have an effect on any supplement dosages of vitamin D. Toxic levels of vitamin D rarely occur. They are most likely to occur in people who take too many vitamin D supplements. An overabundance of vitamin D in the body can lead to a condition called hypercalcemia. This condition is marked by excessive levels of calcium in the blood.
APOE4
The ketogenic diet has been used under medical supervision to reduce seizures in children with epilepsy who do not respond to other forms of treatment. There is a lot of research into its effects on brain health, particularly Alzheimer’s. Our brains use glucose as their main fuel source. If glucose is not available, they can switch to using ketones.
In Alzheimer’s disease, the ability of the brain to use glucose for energy is impaired. However, its ability to use ketones remains equal to that of a healthy brain. This is why a ketogenic diet may aid those already suffering from Alzheimer’s but be contraindicated as a preventative measure. Both animal and human trials have shown ketogenic diets have slight beneficial effects in mild-to-moderate Alzheimer’s disease.
Studies that directly supplement ketones in the form of medium-chain triglycerides (MCT) oils have also been promising. Unfortunately, early studies indicate that cognitive improvements from MCT supplementation are weaker in those with APOE4 variations. This suggests a ketogenic diet and MCTs may not be as effective in APOE4 carriers.
Other diseases of interest include; cancer, polycystic ovary disease and Lou Gehrig’s disease.
What does this mean for you?
If you have gene variants that primarily have no effect on your saturated fat metabolism, then you can incorporate saturated fats and foods that contain them into your diet. 
However, if you primarily have gene variants that alter saturated fat metabolism, it would be ideal to minimize these fats.
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