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Excess body weight is responsible for about 11% of cancers in women and 5% of men. Did you know that the risk for postmenopausal breast cancer is 1.5 times higher in overweight women and 2 times higher in women with obesity? Let’s understand more about how obesity contributes to breast cancer risk. 

How Does Body Weight Affect Breast Cancer Risk?

Being overweight or obese increases the risk for breast cancer, especially in postmenopausal women. Your Body Mass Index (BMI) determines if you have a healthy weight, are overweight, or are obese. 

A BMI between 18 and 24.9 is considered healthy. A BMI between 25 and 29.9 means that you are overweight. If your BMI is higher than 30, it could indicate obesity.

Women with a BMI over 25 are at an increased risk of developing breast cancer than those with a healthy weight. In addition, this risk is exceptionally high after menopause. Being overweight or obese also increases the risk of breast cancer recurrence.

The exact link between increased weight and breast cancer risk is complicated and multifactorial. The high risk appears to be connected to the estrogen production by the fat cells. 

In premenopausal women, estrogen is mainly produced by the ovaries. However, in postmenopausal women, adipose tissues or fat tissues is the main source of estrogen production.

The number of fat cells is higher in overweight or obese women. This results in increased estrogen production, which is a risk factor for breast cancer development. This is especially of significance for Hormone-Receptive breast cancers that develop and grow on exposure to estrogen.

It has been found that women who are obese after menopause are at a 30% higher risk of developing breast cancer. Gaining more than 22 pounds after menopause can increase the risk of breast cancer by 18%.

Obesity And Breast Cancer Risk

Obesity and Breast Cancer Risk in Premenopausal Women

Studies report an association between obesity and a lower risk of Estrogen-Receptor Positive (ER-Positive) breast cancer but a higher risk of ER-negative and Triple-negative breast cancer in premenopausal obese women. 

In addition, a study from the Breast Cancer Surveillance Consortium database showed that obesity is associated with an increased risk for Inflammatory Breast Cancer (IBC) in premenopausal women.

Obesity and Breast Cancer Risk in Postmenopausal Women

The Million Women Study followed 1.2 million UK women ages 50 to 64 years for a mean of 5.4 years. Out of these, 45,037 women had breast cancer. The study identified a nearly 30% higher risk of developing postmenopausal breast cancer with obesity.

A meta-analysis of 34 studies reported that the risk of postmenopausal breast cancer increases with every 5kg/m2 increase in BMI. 

Risk Of Breast Cancer Mortality In Obese Patients

Obesity affects the prognosis and survival rate of breast cancer patients. A recent study found that obese women with breast cancer experienced an 11% decrease in overall survival rate, irrespective of their menopausal status. 

Besides breast cancer, obesity is a risk factor for type 2 diabetes and heart diseases - the latter seems to be the leading cause of mortality in women with early-stage breast cancer.

It has also been observed that obese women with breast cancer are more likely to experience complications during surgery and radiation. 

In addition, systemic chemotherapy and endocrine therapy for treating breast cancer are less effective in obese women, further reducing prognosis and survival rate.

Breast cancer-specific mortality among obese women is 1.3 times higher compared to women with a normal BMI

The mortality rate in obese women is also dependent upon the type and characteristics of the tumor. For example, obese women with Luminal A and Luminal B breast cancer were 1.8 and 2.2 times more likely to die from cancer than normal-weight women. 

However, obesity was not associated with breast cancer-specific mortality among women with HER2- and triple-negative tumors.

Genetic Factors That Influence The Relationship Between Obesity And Breast Cancer Risk

The BRIP1 Gene

BRCA1 Interacting Helicase 1 (BRIP1) is located on chromosome 17 and, along with the BRCA1 gene, helps repair any damage to the DNA. It is also responsible for maintaining chromosomal stability.

rs16945628 is a Single Nucleotide Polymorphism (SNP) in the BRIP1 gene. The TT genotype of this SNP is associated with an increased risk of breast cancer in women with a BMI of ≧25 kg/m2.

The IGFBP3 Gene

Insulin-like Growth Factor Binding Protein 3 or IGFBP3 gene is located on chromosome 7 and participates in cell growth, multiplication, and differentiation, and cancer development in the breast tissue. 

rs2854744 is an SNP in the IGFBP3 gene linked to the risk of breast cancer. The CC genotype of this gene significantly increases the risk of breast cancer compared to the AA genotype. This increase was found to be more pronounced in older women.

Studies also showed that women carrying the AC+CC genotypes of the IGFBP3 gene had a larger tumor size in the breast.

Non-Genetic Factors That Influence The Relationship Between Obesity And Breast Cancer Risk 

Obesity is a critical non-genetic risk factor for breast cancer. 

Other factors that increase breast cancer risk in obese women are:

Does Weight Loss Reduce Breast Cancer Risk?

According to a 2019 study, sustained weight loss is associated with lower breast cancer risk for women aged 50 years and older

The researchers looked at 180,885 women from 10 studies. The women's weights were recorded 3 times over a period of 10 years; once when they enrolled and once every 5 years.

Weight changes of 2 kilograms or less (about 4.4 lbs) were counted as stable. 

The study reported the following*:

*Compared with those whose weight was stable.

The study did not include women on postmenopausal hormone therapy, and the results were more prominent in obese or overweight women.

Despite this, the study suggests that even a modest amount of sustained weight loss can lower your breast cancer risk and improve survival rate, if diagnosed with breast cancer.

Recommendations to Reduce Breast Cancer Risk

Summary

  1. Being overweight or obese increases the risk of developing breast cancer. This risk is exceptionally high in postmenopausal women.
  2. An increase in weight increases fat cells in the body and a subsequent rise in estrogen levels. Exposure to estrogen increases the risk of breast cancer development.
  3. Women with BMI over 25 have a higher risk for breast cancer. 
  4. Obese premenopausal women have a lower risk for ER-Positive breast cancer but an increased risk for ER-negative and triple-negative breast cancer.
  5. Breast-cancer-specific mortality among obese women is 1.3 times higher than in women with normal BMI.
  6. Few genes like BRIP1 and IGFBP3 are associated with breast cancer risk in obese women.
  7. Other factors like lack of physical activity, hormone replacement therapy, reproductive history, alcohol consumption, and smoking increase breast cancer risk in obese women.
  8. According to a study, sustained weight loss in women over 50 can help reduce breast cancer risk compared with women whose weight was stable.

References:

For years, diets called for the elimination of fats, urging us to move towards low-fat alternatives. While, like any other nutrient, overdoing fats can lead to weight gain, cutting out dietary fats need not necessarily result in weight loss. Replacing bad fats (trans fats, saturated fats) with good fats (mono and poly-unsaturated fats) comes with benefits that extend beyond weight loss. This article covers everything there is to know about incorporating monounsaturated fats in your diet. 

Monounsaturated Fatty Acids

Fats are an important component of any meal as they help in absorbing fat-soluble vitamins and minerals.

They also store energy within the body, protect vital organs, and help in muscle movement.

Fats are chains of carbon and hydrogen, and depending on the length of these chains and the arrangement of these atoms, they are classified into different types of fats.

The “mono” in monounsaturated fats represents the single double bond that is found in its chemical structure.

Owing to this chemical structure, monounsaturated fats are often liquid at room temperature.

History Of Fat Consumption

Anthropologists claim that the diet of early humans was more similar to that of modern chimpanzees. They consumed fruits, vegetables, leaves, flowers, and meat. It is believed that meat was first consumed about 2.6 million years ago.  

However, our early ancestors engaged in scavenging food rather than hunting. They consumed the edible portions of flesh that were left behind by the predator. Jesicca Thompson, an anthropologist from Yale University, says that the early humans consumed bone marrow stuck in between the bones of the dead animal rather than the “meat.” The marrows are rich in fat content. Thompson claims that it was around this time that humans started adding fat-rich food to their diet. 

Modern-day diet has monounsaturated fats in vegetable and seed oils. A study confirmed that the first use of vegetable oil, particularly olive oil, was seen around 8000 years ago in the Middle East. But it was in the 1600s when people started making oil from vegetables. 

The 1800s saw the widespread use of vegetable oil as the commonly used whale oil became expensive. In the process of making affordable soaps using cottonseed oil, two industrialists in Cincinnati took the opportunity to introduce it in the food industry. In a few years, animal fats were replaced by vegetable cooking oils, and we can still find them in our kitchens today. 

Studies observed that people from the Middle East or the Mediterranean countries had a lower risk of heart diseases, despite consuming a fat-rich diet. Further investigation showed that their diet included olive oil and other seed oils as their main source of fat and not animal fat. This could mean that the health benefits come from unsaturated fats rather than saturated fats from animals. 

Importance of Monounsaturated Fatty Acids

A study consisting of around 840,000 adults aged 4-30 years found that the consumption of monounsaturated fats reduced the risk of heart disease by 12%, compared to the control group (little to no monounsaturated fats consumption)

Monounsaturated fats improve overall health by:

Sources of monounsaturated fats are olive oil, peanut oil, avocados, nuts, safflower, and sunflower oils.

Is There A Relationship Between Monounsaturated Fats And Weight Gain?

Weight gain is caused when the calories consumed are greater than the calories burnt.

All fats provide the same amount of energy, which is about nine calories per gram.

Based on your lifestyle and your basal metabolic rate, including the right amount of fat in your diet, can help with weight management. 

Even though weight gain/loss is a simple equation of calories in and out, the quality of the food you eat as part of your diet is very important.Some studies have shown that if calorie intake remains the same, diets high in MUFAs lead to weight loss and could even be more effective than a high-carb diet.

What Is The Recommended Amount Of Monounsaturated Fat Intake?

It is recommended to use monounsaturated fats as a replacement to saturated or trans-fats as much as possible.

The 2015 Dietary Guidelines for Americans suggest that fats should be limited to 25 to 30% of the total daily calories; this includes all types of fats.

How Do Genes Affect The Relationship Between Monounsaturated Fats And Weight?

ADIPOQ

This gene is involved in the control of fat metabolism (break down) and insulin sensitivity (how well your body responds to insulin) in the body.

Changes in this gene directly affect anti-diabetic, anti-atherogenic (preventing fatty deposit formation), and anti-inflammatory activities.

The gene codes for a protein called the adiponectin, that is involved in aids fatty acid breakdown. Higher the adiponectin levels, more efficient the fatty acid breakdown.

Decreased adiponectin levels are thought to play a central role in obesity and type 2 diabetes.

Changes in lifestyle, such as incorporating exercise and a following balanced diet, that result in weight loss, can lead to an increase in adiponectin concentration and increase insulin sensitivity.

rs17300539

A study found that a variation rs17300539 in the ADIPOQ gene can lead to a difference in blood adiponectin levels.

Individuals with a G allele have lower blood adiponectin levels when compared to those with an A allele. Carriers of the A allele (AA/AG), therefore, had lower weight, BMI, waist, and hip circumferences.

While considering the monounsaturated fats intake of greater than 13% of the total energy intake, the A allele carriers had a considerably lower BMI compared to GG carriers.

This shows a relationship between the effect of a gene on monounsaturated fats intake and weight.

NR1D1

NR1D1, also known as Rev-ErbA alpha, is present in the liver, skeletal muscles, adipose (fat) tissues, and the brain in mammals.

Adipogenesis is the process by which adipocytes, or fat cells are formed.

Rev-ErbA alpha includes adipogenesis and could be a potential target for novel anti-obesity treatments. 

rs2314339

A study analyzed the association between NR1D1, monounsaturated fats intake, and weight in North American and Mediterranean populations.

People with the AA and AG types had a lower waist circumference and a decreased risk for obesity than people with the GG type.

The A allele occurrence was also significantly low in the ‘abdominally obese’ group.

There was also a significant interaction for obesity with NR1D1 and monounsaturated fats intake in the Mediterranean population.

Individuals with the A allele had higher protection against obesity with diets rich in monounsaturated fats. (>55% of total fat).

PPARG

PPARG is a gene predominantly present in adipose tissue. It plays a role in adipocyte differentiation (converting one type of cell to another), regulating glucose levels, and insulin signal transduction (communication between two cells).

A change in this gene has been studied to play a role in increased sensitivity to insulin and a more favorable lipid profile.

rs1801282

A study recruited overweight subjects between the ages of 20-65 years in southeastern Spain.

They analyzed the subjects as they underwent a treatment program for obesity.

This included analyzing the diets and the number of calories expended during exercise.

They found a gene-diet interaction between PPARG and monounsaturated fats intake.

People who had the G allele (CG/GG) were significantly less obese than those with the C allele (CC) - when monounsaturated fats intake was high (>56% of total fat).

This difference disappeared in low monounsaturated fats diets. 

Overall, in each case, diets with high monounsaturated fats intake (>55% of total fat) resulted in a greater weight loss in individuals.

Food Sources Of MUFA

Most foods have a combination of all types of fats. Foods and oils that have a higher percentage of MUFA are:

Summary

Fats are a necessary component in a balanced diet. However, not all types of fats are healthy. While saturated fats are the ‘bad fats,’ the unsaturated fats are ‘good fats.’ Monounsaturated fats or MUFAs are fats joined by a single bond. They help reduce the risk of health conditions like diabetes and cancer. They also enhance insulin sensitivity and, therefore, play a role in weight management. Several genes ADIPOQNR1D1, and PPARG, mediate how your body responded to MUFAs in terms of weight gain. People with certain types of these genes tend to benefit more from MUFA consumption in terms of weight loss and can include more MUFA-rich foods in their diets. Some food sources of MUFAs include avocados, olive oil, peanuts, and eggs. Even though MUFAs are present in certain animal sources like red meat, their benefits are negated by the saturated fats in them.

Reference

  1. https://www.nature.com/scitable/knowledge/library/evidence-for-meat-eating-by-early-humans-103874273/
  2. https://insidescience.org/news/importance-fat-early-human-evolution
  3. https://www.academia.edu/9517113/Olive_oil_storage_during_the_fifth_and_sixth_millennia_BC_at_Ein_Zippori_Northern_Israel
  4. https://www.health.harvard.edu/staying-healthy/the-truth-about-fats-bad-and-good/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198773/
  6. https://www.healthline.com/health/what-is-basal-metabolic-rate
  7. https://www.medicalnewstoday.com/articles/323027
  8. https://www.medicinenet.com/script/main/art.asp?articlekey=17982
  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486142/
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753535/
  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059404/
  12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951915/

Carbohydrates are one of the most prominent food groups in the diet. They are present as sugars, starches, and fiber in food. Glucose molecules are linked together to form starch and fiber. When carbohydrates enter the body, the fiber goes undigested, while the sugar and starch are broken down into glucose.  Glucose provides the energy required for bodily functions.  

Carbohydrates are commonly associated with weight gain. However, the right kind of carbs in the right amounts can earn a rightful place in your diet. 

Types Of Carbohydrates

Carbohydrates are subdivided into three categories depending on the number of sugars present and the nature of the chemical bonds between them.

Different types of carbohydrates

Although this is the conventional way of classifying carbohydrates, a more useful approach would be to classify them as refined and whole carbohydrates.

Whole carbohydrates include vegetables, legumes, whole fruits, and grains, which are unprocessed and thus have their nutrient content intact.

The stripping of nutrients in refined carbohydrates as a part of processing makes them 'empty calories.' This removal of the nutrients results in rapid absorption and metabolism of these carbohydrates. This results in spiked sugar levels and unstable energy levels.

The Story Behind Carbohydrates

Previous studies on the development of the brain and other human traits suggest that the shift from plant-based to meat-based diet played a critical role. Since then, a lot of evidence has come to light that indicates the involvement of plant-based carbohydrates in meeting the demands of the growing brain.

Further, the role of cooking in improving the digestion and breakdown of carbohydrates has also been factored in. 

According to Mark Thomas, an evolutionary geneticist from University College London, the brain's size started significantly increasing only around 800,000 years ago - which is speculated to be the time period where the usage of fire started. 

What does this mean?

Glucose is the main source of energy for the brain. When the cooked vegetables were consumed, the body had to put in much less work to convert the carbohydrates to glucose for feeding the brain.

For example, the starch in cooked potatoes digests 20 times faster than the uncooked ones. This suggests that cooked carbs, which became the major source of energy, contributed to brain growth.

To further investigate the hypothesis, the starch digesting enzyme amylase was studied. An analysis revealed that the genes that produce amylase started evolving to higher numbers around the same time cooking was started.

This was an advantage since more amylase was required to digest the increasing amounts of starch consumed. So, with every mouthful, the brain derived more energy from the starch.

There are still uncertainties about the antiquity of cooking and the reason for the increase in the amylase enzyme gene. However, the above-mentioned correlation cannot be just dismissed as a coincidence!

Genetics Of Weight Gain On Carbohydrate Intake

AMY1 gene

The AMY1 gene encodes the enzyme amylase, which is responsible for the digestion of starch. Salivary amylase is the enzyme found in your saliva, which begins the process of digesting starch in food. It breaks the insoluble starch into smaller soluble forms. High-AMY1-gene copy number (number of copies of a gene) indicates increased secretion of amylase. This results in a faster breakdown of starch. The difference in the copy number of the AMY1 gene is reported to be the genome's largest influence on obesity. According to a recent study, each copy of AMY1 decreases the risk of obesity 1.2-fold.

rs4244372

rs4244372 is a Single Nucleotide Polymorphism (SNP) in the AMY1 gene. The A allele in this SNP is associated with a lower copy number of AMY1 gene, and hence poor starch metabolism. People who have the AA type may tend to put on more weight on carbohydrates when compared to the people who have the TT or the AT type.

Do All Carbohydrates Cause Weight Gain?

Refined carbohydrates cause sudden spikes in sugar levels. As the sugar levels rise, the body produces insulin to regulate them. Insulin converts excess sugar into fat. A higher spike in sugar levels results in increased insulin secretion, which leaves you with excess stubborn body fat. Various studies show that refined carbohydrates are associated with type 2 diabetes and heart diseases.

Whole carbohydrates, also known as complex carbohydrates, have natural fiber components in them. This fibrous part is easy to digest and thus helps us stay full for a longer time. A balanced diet that is rich in natural fiber helps maintain the blood sugar levels in our body. These foods have a low glycemic load. Glycemic load estimates how much a person's sugar level will rise upon consuming food. A low glycemic load indicates longer digestion time and a smaller spike in blood sugar levels.

An ideal whole carb diet contains seeds (chia seeds and pumpkin seeds), grains (quinoa and oats) with fresh vegetables and fruits. Many nutritionists also advise a switch from white rice to brown rice. This is because brown rice is packed with nutrients that help us prevent heart diseases and type 2 diabetes. 

Should You Avoid Carbohydrates Completely?

Other than being an important source of energy to the body, carbohydrates also perform the following functions:

Carbohydrates Help Maintain A Healthy Gut

Research tells us that a fibrous diet can help maintain a healthy gut. Complex carbohydrates contain a sugar component and a fiber component. Fiber is present in two categories, soluble and insoluble. Soluble fiber helps maintain bowel movements, as well as the consistency of the stool. Insoluble fiber relieves constipation and prevents various digestive tract diseases. Studies also show that a diet rich in fiber helps maintain our blood sugar levels and also benefits our heart.

Carbohydrates Influence Heart Health

While refined carbs are not really your heart's best friend, dietary fiber can help maintain blood sugar levels and is heart-healthy. When fiber passes through the intestines, it prevents reabsorption and hence, the buildup of bad cholesterol. This reduces the risk of heart diseases. 

Dr. Tamar Polonsky, MD, from the University of Chicago Medicine, said that foods that contain complex carbs "decrease inflammation and help us decrease the risk of plaque buildup in our arteries." Plaque is the deposition of certain substances in the blood vessels that block the blood flow. This buildup is caused by fat, cholesterol, and calcium that is present in the blood. This can potentially lead to a heart attack or stroke. Polonsky advises us to stick to healthier carbohydrates with less fat and cholesterol to prevent these.

Carbohydrates Help Maintain Muscle Strength

Our body stores the extra glucose in the form of glycogen (another sugar), which is very important to us. When there's no available glucose from carbohydrates, the body breaks down the muscles to generate glucose for energy. To prevent muscle mass loss due to starvation, the consumption of adequate amounts of carbs is essential.

Carbohydrates Can Improve Mental Health

Apart from all the impacts on physical health, research suggests that carbohydrates can improve mental health as well. A study from the Archives of Internal Medicine showed that people who were on a low-carbohydrate diet for a year experienced symptoms of depression and anxiety. 

Food Sources That Have Low Carb Content

The idea behind a low-carbohydrate diet (for weight loss) is that if the body does not receive the extra carbohydrate, no excess fat will be stored. Instead, the fat already present will be burnt for energy. 

Plant Sources Of Low-Carbohydrates Foods

Animal Sources Of Low-Carbohydrates Foods

High-carbohydrate need not necessarily be our enemy. In fact, high carbohydrate foods with adequate fiber are extremely healthy. 

Food Sources Of Complex Carbohydrates

All these foods are rich in fiber and help us from feeling hungry frequently. They also help us maintain good gut and heart health. 

Summary

Carbohydrates are one of the major food groups. There are two types of carbohydrates - whole or complex and refined. Whole/Complex carbohydrates present in food like oats and bananas are healthy, while the refined carbohydrates are "empty calories" that spike your blood sugar levels. The starch in the carbohydrates is digested by the salivary enzyme, amylase, encoded by the AMY1 gene. A higher copy number of the AMY1 gene is considered beneficial, as it results in a faster breakdown of starch. rs4244372 is an SNP in the AMY1 gene associated with the difference in the copy number of the gene. People who have the AA type tend to have a low copy number and hence may be poor digestors of starch. These people are at an increased risk for weight gain on carbohydrate consumption and may benefit from a low-carbohydrate diet. Some low carbohydrate foods include leafy greens, nuts, and olive oil. Animal foods like lean meat and fish are low in carbohydrates. Another option can be switching to a fiber-rich carbohydrate (complex carbohydrates) diet. Fiber is digested slowly and thus keeps you full for longer. Quinoa, buckwheat, berries, and sweet potatoes are good sources of complex carbohydrates.

References:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485469/
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712930/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836142/
  4. https://pubmed.ncbi.nlm.nih.gov/24008907/
  5. https://en.wikipedia.org/wiki/Glycemic_load
  6. https://www.hsph.harvard.edu/news/features/gnet-brown-rice-diabetes/
  7. https://pubmed.ncbi.nlm.nih.gov/21332763/
  8. https://pubmed.ncbi.nlm.nih.gov/23422921/
  9. https://www.uchicagomedicine.org/forefront/heart-and-vascular-articles/the-benefits-carbohydrates-can-have-on-heart-health
  10. https://pubmed.ncbi.nlm.nih.gov/19901139/

A research study on the data from Adolescent Brain Cognitive Development (ABCD) Study suggests a relationship between certain regions in the brain and weight gain among children and adolescents. The study explored the relationship between “reward region” and food processing and suggests that this region may predict obesity in children. 

Childhood obesity is a serious problem in the United States, putting children and adolescents at risk for poor health. Overweight children are much more likely to become overweight adults unless they adopt and maintain healthier patterns of eating and exercise.

Previous research has identified a region in the brain associated with overeating or unhealthy eating behavior.

The Reward System Region In The Brain

Almost all our actions are driven by two things: Necessity and Reward. An activity can be considered a reward when it motivates us or gives us pleasure. Neurons, the brain's fundamental working unit, communicates this "reward" using dopamine, which is popularly known as the "happy hormone." 

Incidentally, food-reward is common in animal training routines. An animal is rewarded with a treat when it performs certain actions and this programming of food-reward is routinely used by animal trainers in zoos and entertainment venues and other animal training facilities.

Hedonic Hunger

Hedonic hunger describes eating for pleasure than hunger - to enjoy the taste rather than to meet the body's energy needs. This pleasure eating triggers the brain's reward system region, which can lead to overeating - a common cause of obesity.

The Study

"The ABCD study or the Adolescent Brain Cognitive Development Study is the largest long-term study of brain development and child health in the United States." The study was done on over 10,000 children from ages 9-10 and was followed up through early adulthood. 

Using the data from this study, the researchers attempted to investigate the relationship between the reward system region in the brain (called the nucleus accumbens) and eating behavior by examining 5300 research participants.

It was observed that when 2000 participants returned for a one year follow up, the waist circumference had increased by an average of 2.76 centimeters per participant.

The cell density (number of cells for a given area) in the reward region of the brain was examined using a noninvasive MRI technique. 

The MRI revealed changes in the cell density that reflected the increase observed in the waist circumference. 

The study speculates that the increase in this cell density can be because of an inflammation caused due to a diet rich in high-fat foods. 

The findings essentially tell us that a vicious cycle of pleasure eating leading to changes in brain, in turn leading to overeating and increasing the risk of obesity.

Not all children who carry a few extra pounds can be classified as obese. Weight fluctuations are commonly observed in the growing stage of children. Before you decide on dietary changes for your child based on any weight gain you see, it's best to consult a doctor. The doctor may use growth charts, calculate the BMI and, take a family history, and, if necessary, may order a few tests to outline the issue behind the weight gain. 

References

  1. https://www.sciencedaily.com/releases/2012/05/120503103446.htm
  2. https://en.wikipedia.org/wiki/Dopamine
  3. https://abcdstudy.org/about/

Carbohydrates are one of the main classes of food. It is the main source of energy for the body. They are a group of organic compounds present in the form of food in cellulose, starch, and sugar. They are called carbohydrates, as they contain hydrogen and oxygen in the same ratio as water (2:1). These are then broken down to release energy.

Due to the association of carbohydrates with weight gain, the carbs may disguise as an enemy to a healthy diet. However, the right kind of carbs in the right amounts can definitely earn a rightful place in your diet. 

A healthy weight is an important element of good health. The amount of food you eat and what you eat is important for maintaining a healthy weight.

For years, there was a myth that a low-carb diet is the best way to lose weight, but a growing body of evidence suggests otherwise.

Types of carbohydrates

Carbs are sub-divided into three categories depending on the number of sugars present and the nature of the chemical bonds between them.

Analyze Your Genetic Variants For Weight Gain On Carbohydrate Intake

Although this is the conventional way of classifying carbs, a more pragmatic approach would be to classify them as refined and whole carbs.

Whole carbs include vegetables, legumes, whole fruits, and grains, which are unprocessed and thus have their nutrient content intact.

The stripping of nutrients in refined carbs as a part of processing makes them count as 'empty calories.'

This removal of the nutrients results in rapid absorption and metabolism of these carbohydrates.

This results in spiked sugar levels and unstable energy levels, the latter of which causes “sugar rush” after consuming sugar-rich foods.

The refined or the sugary carbs are simple carbohydrates that the body quickly absorbs.

Their metabolism occurs rapidly, which results in major swings in the blood glucose levels. This induces hormonal and metabolic changes that can promote overeating.

Are carbohydrates bad?

Not all carbohydrates are bad for health.

Unprocessed carbs that are present in vegetables, fruits, and grains are healthy.

Studies reveal that these improve metabolization and help in weight loss.

Another class of carbs, the processed ones, are unhealthy because they lose the fiber during processing and contain no essential nutrients.

Examples of these include white bread, white rice, and the like.

Intake of foods containing processed carbs can result in weight gain and increased risk of type 2 diabetes.

Studies show that high unprocessed carbs in the diet can lead to a craving for more carbs, and people tend to get caught in the vicious cycle.

Thus, making changes to your diet by including more of unprocessed carbs can be a healthy choice.

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Everything You Need To Know About Using Fiber For Weight Loss

Carbohydrates intake and weight gain tendency: What’s the genetic link?

Studies have shown that there is a link between genetic factors and dietary factors such as weight loss, weight gain, obesity.

Nearly 70% of the world population carries the gene for obesity. This explains why obesity is growing rapidly around the world.

However, people can reverse this gene's effect by exercising and including more protein in their diet.

Gene 1: FTO

A study has found an association between the FTO gene and the intake of carbohydrates.

The individuals with the A variant were found to have a higher risk of obesity than ones with the CC wild type.

The FTO gene has a negative association with over-eating.

Gene 2: AMY1

About 23% of the global population carries a variant in the AMY1 gene, which shows an association with low copy numbers of the gene and reduced ability to digest starch. 

70% of people from agricultural populations have an AMY1 copy number variant, which shows an association with better starch digestion and lower risk of obesity when compared to 37% of non-agricultural populations.

Can a DNA test help you lose or gain weight?

The conventional diet plans and workout regimes architected for weight loss need not help everyone achieve their desired goals.

There is a multitude of factors that influence weight loss, including a person’s lifestyle, genetic makeup, and the environment.

Your genes can influence how you metabolize the nutrients you get from your diet. This directly has a role to play in weight gain/loss.

For instance, some people may possess a genetic variant that aids in the faster metabolization of carbohydrates, while others may carry a variant that will help in faster break-down of saturated fats.

You can leverage such genetic information to adopt a practical and personalized weight loss plan.

While genetic tests may not lay out the A-Z of weight loss, it certainly helps you pin the right path for your weight loss journey.

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Published on June 17, 2020

What is type II diabetes?

Diabetes mellitus type II is a long term metabolic disorder that results in high blood sugar, insulin resistance, and/or lower insulin levels.

According to the American Diabetes Association, 9.3% of the US population has this disorder. 

Formerly known as adult-onset diabetes, it occurs most often in middle-aged and older people. 

Over time, high blood glucose can cause serious complications with the heart, eyes, kidneys, nerves, gums, and teeth. 

What causes type II diabetes?

The special cells in the pancreas, called the beta cells produce a hormone called insulin. 

Insulin moves blood sugar or glucose into the cells. 

In type 2 diabetes, the fat, liver, and muscle cells respond incorrectly to insulin. 

This is called insulin resistance. 

The glucose is incapable of entering the cells, and a high level of sugar builds up in the blood. 

This is known as hyperglycemia. 

Insulin resistance is the most common cause of type 2 diabetes.

But sometimes, type 2 diabetes can be caused by decreased production of insulin by the beta cells.

What are the symptoms of type 2 diabetes?

Type 2 diabetes can cause serious complications, so it is essential to identify the symptoms as early as possible.

Most of the symptoms are a result of increased blood sugar levels. These include:

  1. Increased thirst
  2. Increased hunger
  3. Frequent urination
  4. Fatigue
  5. Dry mouth
  6. Unexplained weight loss
  7. Blurred vision
  8. Headache

Other symptoms of type 2 diabetes include:

  1. Slow-healing sores or cuts
  2. Velvety dark skin changes of the neck, armpit, groin
  3. Numbness and tingling of hands and feet
  4. Decreased vision

What are the type 2 diabetes risk factors?

Chances of developing type 2 diabetes depend on a combination of risk factors, including genes and lifestyle.

While the genetic risk factors cannot be changed, making the required changes in our lifestyle is very much within our hands. 

You are more likely to develop type 2 diabetes if you

Hand-Picked article for you: Have Your 23andMe Raw Data? Use It To Get 500+ Health-Related Genetic Traits!

The genetic component to type II diabetes

Research has identified at least 150 genetic variations associated with the risk of developing type 2 diabetes. 

Each person possesses variations that can either increase or decrease the risk. 

The combination of these variations determines a person's likelihood of developing the disease. 

The genetic variations may directly or indirectly affect the following:

However, for many of the variations associated with type 2 diabetes, the mechanism by which they contribute to the disease is unknown

Gene 1: IGF2BP2

IGF2BP2 gene encodes a protein that binds the 5’ UTR of insulin-like growth factor 2 mRNA and regulates its translation.

It plays an important role in metabolism, and variation in this gene is associated with susceptibility to diabetes.

Studies have shown an increased risk of T2D for those with the rs4402960 polymorphism.

In the case-control study, the carriers of TT genotype at rs4402960 had a higher T2DM risk than the G carriers (TG + GG)

rs4402960

[table “90” not found /]

In conclusion, the analysis suggested that rs4402960 polymorphism in IGF2BP2 is associated with elevated T2D risk, but these associations vary in different ethnic populations. 

Gene 2: PPARG

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a critical role in regulating insulin sensitivity and glucose homeostasis and can be associated with improved insulin sensitivity.

Research has shown that PPAR-γ directly activates GLUT2 and β-glucokinase (important to glucose homeostasis)

Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases, including obesity, diabetes, atherosclerosis, and cancer.

Inactivating mutations of the gene encoding PPAR gamma are associated with insulin resistance type 2 diabetes.

rs17036314 is an SNP in the PPARG gene found to increase the chance of type 2 diabetes.

rs17036314

[table “91” not found /]

Gene 3: SLC30A8

SLC30A8, a zinc transporter gene, is associated with type 2 diabetes.

It is involved in the accumulation of zinc in intracellular vesicles.

This gene is expressed at a high level only in the pancreas, particularly in the islets of Langerhans.

The common polymorphism rs13266634 was associated with lowered beta-cell function and a 14% increase in diabetes abundance per risk (C) allele.

This variant encodes a tryptophan-to-arginine switch at position 325 in the protein.

This results in reduced zinc transport activity and, consequently, decreased intragranular zinc levels. 

The SLC30A8 polymorphism is found associated with reduced insulin secretion, but not with insulin resistance.

rs13266634

[table “92” not found /]

Gene 4: HHEX

HHEX gene encodes a member of the homeobox family of transcription factors. Its polymorphisms show association with type 2 diabetes.

The major role of HHEX protein is interacting with signaling molecules.

It plays a role in embryonic development of the pancreas, liver, and thyroid.

A study linked that polymorphism rs7923837 is associated with impaired insulin response.

The risk allele of rs1111875 and rs7923837 in the HHEX gene are associated with reduced beta-cell secretion capacity.

rs1111875

[table “93” not found /]

rs7923837

[table “94” not found /]

Gene 5: TCF7L2

The TCF7L2 gene plays a role in controlling blood sugar levels.

It is involved in adipogenesis (formation of fat cells) and is associated with glucose intolerance and impaired insulin secretion.

The SNP within the TCF7L2 gene, rs7903146, plays a role in this association.

The risk allele results in the overexpression of the gene in the pancreatic beta cells, thus reducing insulin secretion.

The reduced insulin secretion explains the increased hepatic glucose production. 

In conclusion, the increased risk of T2D conferred by variants in TCF7L2 involves the enhanced expression of the gene in islets and impaired insulin secretion.

rs7903146

[table “95” not found /]

Gene 6: KCNJ11

KCNJ11, in tandem with several other genes, mediates the regulation of insulin released.

Reduced expression of KCNJ11 may increase the risk of type II diabetes.

The rs5219 A allele plays a crucial role in insulin secretion by decreasing the ATP sensitivity of the Potassium ATP channel and suppressing insulin secretion. However, the mechanism involved is still unclear. 

rs5219

[table “96” not found /]

You may also be interested in Diabetes: A Genetic Overview

What do I do with my genetic information?

Type II Diabetes is a complex condition with several contributing factors, genetics included.

Certain genetic predispositions increase the individual's risk of developing the disorder; however, it is not a guarantee that the person will go on to develop that condition.

This is because other factors play a role in its onset.

Knowing your genetic makeup empowers you with information to reduce the risk of developing type II diabetes by altering the factors that are in your control.

How to prevent the onset of type II diabetes?

Research such as the Diabetes Prevention Program shows that you can do a lot to reduce your chances of developing type 2 diabetes. Here are some things you can change to lower your risk:

You may be able to prevent or delay diabetes by losing 5 to 10 percent of your current weight.

For example, if you weigh 250 pounds, your goal would be to lose between 12.5 to 25 pounds.

Insulin resistance reduces with regular exercises and better utilization of glucose by the cells. 

Choose foods that have lesser fat content.

If losing weight is the goal, a high-fiber, low-fat diet may help you.

Drink water in plenty and stay away from those soft drinks!

Hand-picked content for you: Drinking 2 or more sugary drinks per day doubles diabetes risk

Diabetes-friendly diet:

Altering one's diet is one of the best ways to prevent type 2 diabetes, and this can be done by including and excluding a few items in the diet.

Foods to eat:

A diet of beans, vegetables, nuts, seeds, and fresh fruit can prevent type II diabetes.

High nutrient, low glycemic load foods are the best food for diabetics and those looking to prevent it.

An analysis found that leafy vegetable intake was related to a 14% decrease in the risk of type 2 diabetes.

They have close to no effect on blood glucose and are rich in fiber and phytochemicals.

Beans have low glycemic load due to their increased fiber and resistant starch (carbohydrates that are not broken down in the small intestine).

Eating three servings of fresh fruit each day results in an 18% decrease in the risk of diabetes.

Foods to Avoid:

Foods that increase blood sugar levels or reduce sensitivity to insulin increase the risk for type 2 diabetes. These include:

Fibers slow down the absorption of glucose into the blood.

However, these foods are devoid of sugar and can cause a sharp increase in blood glucose levels.

They increase the chances of getting type 2 diabetes in the long run.

This leads to increased glucose levels and a greater risk of diabetes.

A meta-analysis conducted concluded that:

You can use your 23andMe DNA raw data to learn about your type 2 diabetes risk

Xcode Life Gene Health Report analyzes the genetic variants for type 2 diabetes, anxiety, heart disease, and more than 45 categories of health-related traits.

The Fat Mass and Obesity gene (FTO) is associated with the synthesis of the FTO enzyme, also known as the alpha ketoglutarate dependent dioxygenase. FTO gene expression has been shown to be upregulated in the hypothalamus of the brain after food deprivation, which is associated with increased consumption of high calorie foods. There are 3 SNPs that we analyze in association with weight management and carbohydrates, fiber, protein or saturated fat intake- rs9939609, rs8050136 and rs11076023.

Association with a tendency to overeat (Weight Management):

In a review study, children with the A variant of the gene were shown to be associated with greater intake of biscuits when compared with children with the T variant (rs9939609). Adults with the A variant (rs9939609) were also shown to have altered post prandial satiety (feeling of being full) levels. In a similar study conducted to identify the association between post prandial satiety and rs9939609, people with the A variant of the fat gene were found to be associated with low sensation of feeling full after a meal.  

Loss Of Control Over Eating

In a study conducted on 289 youth, people with the A variant (rs9939609) of the gene had a greater tendency to eat more fat than people with the T variant (rs9939609), with 37.4% of people with the A variant reporting loss of control over eating when compared with 18.8% of people with the T variant. Subsequently, the study showed that people with the A variant of the gene had a significantly greater body mass index.

TV advertisement and overeating

TV advertisements could also induce people to overeat, but the extent of overeating is shown to be associated with the fat gene variant carried by the individual. A study was conducted on 200 children post lunch, involving screening of a 34 minute television program, which also included food advertisements and toy advertisements. Children with the A variant (rs9939609) of the gene consumed significantly more snacks when they were exposed to food advertisements.

Association with Carbohydrate Intake and Weight Gain Tendency:

In a study conducted on 1618 people from an Asian Indian population, people with the A variant (rs8050136) of the gene had a 2.46% higher risk of obesity when compared to people with the C variant among people on a high carbohydrate diet. In the same study, it was found that among people who were inactive, people with the A variant were found to be associated with 1.89 times increased risk for obesity.

Association with Fibre Intake and Weight Loss Tendency:

In the study on 1618 people from an Asian population, people with the A variant (rs11076023) of the gene were shown to be associated with 1.62cm lower waist circumference than people with the T variant of the gene.

Association with Saturated Fat Intake and Weight Gain Tendency:

In a study conducted to identify the association between fat intake, FTO genotype (rs9939609) and body fat percentage, people with the T variant did not show an increase in body fat percentage with increase in fat intake, but people with the A variant were shown to be associated with increased body fat percentage with increased fat intake.

In a study conducted on 4839 men and women on a high fat diet, people with the A variant (rs9939609) were shown to be associated with higher BMI and were twice as likely to be obese when compared with people with the T variant.

Association with Protein Intake and Weight Loss Tendency:

In a study conducted on 737 overweight adults, people with the A variant of the gene (rs9939609) were shown to be associated with a reduced food craving on a hypo-caloric and a high protein diet.

Association with Type 2 Diabetes:

In a study conducted on 2577 Korean study participants, it was found that people with the A variant (rs9939609) of the fat gene were associated with increased risk for obesity and, thereby, an increased risk for diabetes. In a similar study conducted on 4,189 Han Chinese individuals, people with the A variant of rs9939609 and A variant of rs8050136 were shown to be associated with type 2 diabetes and obesity in the Asian population.

Does your 23andme, Ancestry DNA, FTDNA raw data have FTO gene variant information?

CHIP VersionFTO SNPs
23andMe (Use your 23andme raw data to know your FTO Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your FTO Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your FTO Variant)
OmniExpress microarray chipPresent
Genotype (rs9939609)PhenotypeRecommendations
AA[Limitation] More likely to have higher risk for obesity. [Limitation] More likely to have higher fat percentage on a high fat diet [Limitation] More likely to have higher BMI on a high fat diet [Limitation] More Likely to have loss of control eating episodes [Limitation] More Likely to have higher risk for type 2 diabetes [Advantage] More likely to have lower food craving on a high protein dietA common fat gene myth is that people with this variant are doomed to remain overweight or obese, however, practicing mindful eating and consciously avoiding increased consumption of high fatty food could help in better weight management For people with this variant of the fat gene weight loss can be achieved by balancing food intake with appropriate exercises A high protein diet may be beneficial as it reduces food craving. So foods that turn off fat genes are foods that are rich in protein. Spirulina is a rich source of protein and helps improve satiety
ATModerate risk for obesity 
TT[Advantage] More likely to have lower risk for obesity. [Advantage] Less likely to have higher fat percentage on a high fat diet [Advantage] Less likely to have increased BMI on a high fat diet [Advantage] Less Likely to have loss of control eating episodes [Advantage] Less Likely to have higher risk for type 2 diabetes [Limitation] Less likely to have lower food craving on a high protein dietEnsure a healthy balance between food intake and exercises
Genotype (rs8050136)PhenotypeRecommendation
AA[Limitation] More likely to have increased risk for obesity. [Limitation] More Likely to have higher risk for type 2 diabetesEnsure a healthy balance between food intake and exercises
ACModerate risk for obesityThough the risk for obesity is lower, practise healthy eating practices and ensure sufficient physical activity
CC[Advantage] More likely to have lower risk for obesity. [Advantage] Less Likely to have higher risk for type 2 diabetesThough the risk for obesity is lower, practise healthy eating practices and ensure sufficient physical activity
Genotype (rs11076023)PhenotypeRecommendation
AA[Advantage] More likely to have lower waist circumference on a high fiber dietConsume a fibre rich diet to ensure better weight maintenance Fibre rich foods include black beans, lima beans, broccoli, artichoke and brussels sprouts
ATModerate waist circumference on a high fiber dietA fiber rich diet may not considerably lower weight but it helps in bowel movements and in controlling blood sugar levels
TT[Limitation] More likely to have higher waist circumference than people with the A variant on a high fiber dietA fiber rich diet may not considerably lower weight but it helps in bowel movements and in controlling blood sugar levels

References:

  1. https://en.wikipedia.org/wiki/FTO_gene
  2. https://www.ncbi.nlm.nih.gov/pubmed/19828706?dopt=Abstract
  3. https://www.ncbi.nlm.nih.gov/pubmed/27249024
  4. https://www.ncbi.nlm.nih.gov/pubmed/27274759?dopt=Abstract
  5. https://ajcn.nutrition.org/content/early/2009/09/02/ajcn.2009.27958.abstract
  6. https://www.ncbi.nlm.nih.gov/pubmed/26440677
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777464/
  8. https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-016-0098-6
  9. https://www.ncbi.nlm.nih.gov/pubmed/24622803

Related Links:

  1. https://www.xcode.life/dna-and-health/obesity-and-genetics-variations-in-fto-apoa2-and-apoa5-genes
  2. https://www.xcode.life/dna-and-nutrition/how-much-of-body-weight-is-determined-by-genetics

“Nutrigenetics, fitness genetics, health genetics are all nascent but rapidly growing areas within human genetics. The information provided herein is based on preliminary scientific studies and it is to be read and understood in that context.”

The Melanocortin 4 Receptor gene (MC4R) is associated with the synthesis of MC4R enzyme, a G protein coupled receptor which is found to bind to alpha melanocyte stimulating hormone. Among humans, this gene is shown to be associated with obesity.

There are two SNPs that are used in our panel, rs17782313 and rs12970134

Association with Obesity:

In a study conducted on a North Indian population, people with the C variant (rs17782313) of the gene were associated with elevated obesity risk. In another similar study, the number of people with the C variant was found to be significantly higher among obese people than among others. In the same study, people with the A variant (rs12970134) were shown to have a strong association with obesity.

Association with Physical Activity:

In a study conducted to assess physical activity, people with the C variant of the gene were found to carry out 3.5% less MET/per week when compared to people with other variants of the gene.

Association with Cardiovascular Health:

In a study, people with the C variant of the gene were shown to be associated with increased risk for nocturnal hypertension. In a similar study, people with the C variant of the gene, who had hypertension and were smokers, were shown to be associated with a higher risk for large artery stroke.

Does your 23andme, Ancestry DNA, FTDNA raw data have MC4R gene variant information?

CHIP VersionMC4R SNPs
23andMe (Use your 23andme raw data to know your MC4R Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your MC4R Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your MC4R Variant)
OmniExpress microarray chipPresent

Association with Tendency to Overeat (Fatty Food Preference):

In a study conducted to determine the reward value of food, people with the C variant of the gene were shown to be associated with increased energy intake.

Association with Age and Gender:

In a study conducted to analyze the effect of MC4R gene variant on age and gender, women with the C variant of the gene were shown to be associated with a greater risk of obesity than men. People within 20-40 years were shown to be associated with obesity-related effects of the gene and there was a lower influence of the gene as age advanced.

Genotype rs17782313PhenotypeGenotype
CC[Limitation] More likely to have increased risk for obesity. [Limitation] Less likely to perform physical activity [Limitation] More Likely to have higher nocturnal blood pressure and increased risk for cardiovascular disease [Limitation] More Likely to have increased energy intake and fatty food preferencePractice mindful eating and consciously avoid increased consumption of high fatty food Associated with lower physical activity, so should consciously balance food intake with appropriate exercises. Women show a greater tendency to gain weight than men with this variant. Avoid smoking as it increases risk for stroke
CTModerate risk for obesityPractice mindful eating and consciously avoid increased consumption of high fatty food Associated with lower physical activity, so should consciously balance food intake with appropriate exercises. Women show a greater tendency to gain weight than men with this variant. Avoid smoking as it increases risk for stroke
TT[Advantage] Less likely to have increased risk for obesity. [Advantage] More likely to perform physical activity [Advantage] Less Likely to have higher blood pressure and increased risk for cardiovascular disease [Advantage] Less Likely to have increased energy intake and fatty food preferenceEnsure a healthy balance between food intake and exercises.
Genotype rs12970134PhenotypeRecommendation
AA[Limitation] More likely to have increased risk for obesity.Practice mindful eating and consciously avoid increased consumption of high fatty food
AGModerate risk for obesityPractice mindful eating and consciously avoid increased consumption of high fatty food
GG[Advantage] Less likely to have increased risk for obesity.Ensure a healthy balance between food intake and exercises.


References
:

  1. https://www.ncbi.nlm.nih.gov/pubmed/26226973
  2. https://www.ncbi.nlm.nih.gov/pubmed/26495240
  3. https://www.ncbi.nlm.nih.gov/pubmed/27213003
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816968/
  5. https://www.ncbi.nlm.nih.gov/pubmed/27701175
  6. https://www.ncbi.nlm.nih.gov/pubmed/27730429

Related Links:

  1. https://www.xcode.life/dna-and-fitness/do-you-have-the-obese-gene
  2. https://www.xcode.life/dna-and-nutrition/how-much-of-body-weight-is-determined-by-genetics
  3. https://www.xcode.life/dna-and-health/what-regulates-energy-intake-and-why-does-it-differ-from-person-to-person

Nutrigenetics, fitness genetics, health genetics are all nascent but rapidly growing areas within human genetics. The information provided herein is based on preliminary scientific studies and it is to be read and understood in that context.”

ACE gene: An introduction

ACE gene codes for Angiotensin-Converting Enzyme.

This enzyme is a part of the Renin-Angiotensin System, which is responsible for maintaining blood pressure, and fluid and salt balance in the body.

The enzyme cleaves the protein angiotensin I at a particular site, converting it into angiotensin II.

This angiotensin II brings about constriction of blood vessels, thereby increasing the blood pressure.

ACE gene is located on the long arm of chromosome 17.

Mutations in the ACE gene have been associated with a severe form of the renal disease called renal tubular dysgenesis.

What are ACE inhibitors? 

As the name goes, ACE inhibitors are medications that slow down or inhibit the effects of angiotensin-converting enzyme (ACE).

Such medications are involved in relaxing the blood vessels and reducing blood pressure levels.

They are primarily used as anti-hypertensive drugs.

The ACE inhibitors prevent the angiotensin-converting enzyme from producing angiotensin II.

This reduces blood pressure and makes it easier for the heart to pump blood, thereby improving the functioning of the heart.

ACE inhibitors can be used to treat the following conditions:

Common examples of ACE inhibitors are:

What are the side effects of ACE inhibitors? 

Like any other medication, ACE inhibitors too, have a few side effects. But, most of them are not a cause of worry.

These include:

ACE inhibitors and weight loss 

According to a study conducted by researchers in Australia, it was observed that ACE deficient mice weighed 20% lesser than the mice with ACE activity. It was also observed that the ACE deficient mice had 50% less body fat, especially around the belly area. 

The results from this study have suggested that ACE inhibitors might help in weight loss around the mid-section in humans.

This, along with the other effects of ACE inhibitors, might be cardio-protective.

Handpicked article for you: Is Dr. Rhonda Patrick Diet For You? Analyze Your DNA Raw Data To Find Out Your Nutritional Needs!

Are ACE inhibitors safe for the kidneys? 

ACE inhibitors are cardio and renoprotective.

They reduce systemic vascular resistance in patients with hypertension, chronic renal disease, and heart failure.

ACE inhibitors as we know by now cause a fall in the blood pressure.

Intrarenal efferent vasodilation is also observed along with a fall in the glomerular filtration pressure.

These events are said to be renoprotective.

However, when the glomerular filtration is critically dependent on the angiotensin II-mediated efferent vascular tone, giving ACE inhibitors to the patient can induce acute renal failure.

The systemic and renal hemodynamic consequences, both benefits and adverse effects, are brought about by the depletion of sodium. 

Treating such patients with diuretics and ACE inhibitors, along with some sodium intake restrictions, can improve their therapeutic efficiency.

So, if the patients have a high risk of adverse renal effects to ACE inhibitors, their dosages should be titrated appropriately, and renal function and potassium levels should be closely monitored.

ACE inhibitors vs. beta-blockers 

ACE inhibitors and beta-blockers are both classes of drugs that are used to treat hypertension.

Though their goal is the same, their mechanism of action is entirely different. 

ACE inhibitors work by preventing the conversion of angiotensin I to angiotensin II.

Thus, they cause the relaxation of blood vessels and lower the blood pressure.

Beta-blockers, on the other hand, block epinephrine (adrenaline) and norepinephrine (noradrenaline) from binding to beta receptors on the nerves.

This reduces the heart rate and subsequently lowers blood pressure.

Both these classes of drugs have their side effects and drawbacks.

In most cases, a combination of one or more anti-hypertensive drugs is used to treat high blood pressure.

What is hypertension? 

Hypertension is a widespread and highly prevalent lifestyle disease.

It is a medical term given for consistently high blood pressure over 120mm Hg systolic and 80mm Hg diastolic.

Hypertension is characterized by the flow of blood at high pressure against the walls of the blood vessels. 

As a result, the workload of the blood vessels and the heart increases substantially.

Over a period of time, this force and friction on these tissues end up damaging them, and this can precipitate many conditions.

Some of them include:

What are the leading causes and symptoms of hypertension? 

Hypertension can be of two types: Primary and secondary.

When the rise in blood pressure levels is due to a non-identifiable cause, it is known as primary hypertension.

However, when there is an increase in the blood pressure levels due to an underlying condition, it is called secondary hypertension.

Some common causes of hypertension include:

Though hypertension is often silent, in some cases, the patient does show some symptoms. Like:

What are the four stages of hypertension? 

[table “124” not found /]

Individuals who are in the prehypertension stage can progress to the other stages if immediate action is not taken.

Untreated cases of hypertension can even be fatal.

Diet recommendations to reduce blood pressure

One of the primary causes that result in hypertension is poor lifestyle choices, which includes an unhealthy diet.

So, to reduce the blood pressure levels and maintain it under the limit, certain dietary recommendations should be followed.

What is the DASH diet? 

DASH diet is an acronym for Dietary Approaches to Hypertension diet.

The plan includes adopting a diet which includes fruits, vegetables, whole grains, low-fat dairy, nuts and seeds, legumes, fish, and poultry.

The most important aspect is to eat foods that are rich in potassium, calcium, magnesium, protein, and fiber and avoiding foods rich in sodium.

DASH diet is low salt and low sugar diet that does not allow the intake of desserts, sweetened drinks and beverages, red meat, and processed meats and fats.

The diet allows a maximum of 2000 calories a day, which includes:

  1. 7-8 servings of grains
  2. 4-5 servings each of fruits and vegetables
  3. 2-3 servings of low-fat or fat-free dairy products
  4. 1-2 servings of lean meat or fish 
  5. 4-5 servings of nuts and seeds per week
  6. 2-3 servings of oil or fat 
  7. Not more than five servings of sweets per week 

Can high blood pressure be cured?

In most cases of primary hypertension, blood pressure levels can be brought down by a combination of medications, dietary changes, regular exercise, and lifestyle modifications.

Once the blood pressure has been controlled, the individual can maintain his/her blood pressure levels within a reasonable range by living and eating healthy.

In many cases, a precautionary medication is advised to prevent the blood pressure from shooting up. 

Salt intake and high blood pressure 

Our kidneys are responsible for water and salt regulation.

More the salt we consume, more the kidneys tend to retain water.

The increased water retention results in an increase in our systemic blood pressure.

This leads to increased pressure on the walls of many blood vessels, which may result in organ damage. 

ACE gene and hypertension 

Of the many factors that can cause hypertension, the ACE gene also plays a role.

We know that the blood pressure in the body is controlled by the kidneys.

But, to be more specific, the Renin-Angiotensin System or RAS system is responsible for regulating it.

Some genetic variations are related to the RAS system, the most common one being the insertion/deletion polymorphism of the ACE gene.

So, essentially, the interactions between the ACE I/D polymorphism, sodium intake the RAS system determine your blood pressure and influence the risk of developing hypertension.

rs2106809

It was observed that the DD genotype of ACE and the TT genotype of ACE2 were significantly high in female hypertensives and the T allele of ACE2 was also linked to male hypertensives.

[table “123” not found /]

rs4308

SNP rs4308 is located on chromosome 17.

Presence of the A allele is responsible for the increase in the diastolic blood pressure.

This SNP locus also features as a target of anti-hypertensive drugs.

ACE gene and fitness 

The ACE gene has been linked to athletic performance.

A genetic variation consisting of 287 DNA bases when inserted into the ACE gene causes a decrease in the ACE enzyme activity.

This version of the gene is called the ‘I’ version.

This variation is shown to be present in athletes, especially sprinters.

The presence of this insertion has been seen in many athletes who perform well in endurance sports such as wrestling, swimming, triathlons, etc.

Though the exact mechanism of how the ACE I gene contributes to fitness and athleticism is unknown, it probably has something to do with an increase in the heart rate, blood pressure, and muscle growth during training.

rs4343

SNP rs4343 of the ACE gene has the ‘A’ and ‘G’ allele.

The A allele is associated with the insertion or I variation, whereas the G allele of the gene is associated with deletion or the D variation.

The G allele results in an increased risk of heart disease (GG) whereas, the minor A allele shows an increased association with endurance-based athletes. 

SNP rs4343 has also recently been linked to susceptibility to migraine, where a G/G polymorphism was seen in patients with migraine with aura as compared to patients of migraine without aura.

Does your 23andme, Ancestry DNA, FTDNA raw data have ACE gene variant information?

CHIP VersionVDR SNPs
23andMe (Use your 23andme raw data to know your ACE Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your ACE Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your ACE Variant)
OmniExpress microarray chipPresent

References:

  1. https://ghr.nlm.nih.gov/gene/ACE#synonyms
  2. https://www.ncbi.nlm.nih.gov/pubmed/8879974
  3. https://www.ncbi.nlm.nih.gov/pubmed/17473847?dopt=Abstract
  4. https://www.ncbi.nlm.nih.gov/pubmed/24112034
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972004/
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