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Abstract

Excess sugar in the body or hyperglycemia is a prevalent condition affecting almost 3.5 million people in the US (according to a 2017 report). The Van Andel Research Institute study reports how an excess intake of dietary carbohydrates can damage mitochondrial integrity and, thereby, function.

Introduction

According to the CDC, in 2017-18, the dietary sugar intake of Americans was 17 teaspoons. However, the American Heart Association (AHA) only recommends six teaspoons per day. Sugar is broken down (metabolized) in the body to glucose. 

Now, the regulation of glucose levels in the body is closely controlled. Any imbalance in the glucose level leads to metabolic disorders, most commonly, diabetes. 

Hyperglycemia occurs when the blood glucose concentration rises above 140 mg/dl (7.8 mmol/l).   

Excess glucose levels can lead to insulin resistance, where the cells in your muscles, fat, and liver do not respond to insulin. When this happens, the blood glucose levels begin to rise. Persistent insulin resistance ultimately leads to type 2 diabetes.

Mitochondrial Dysfunction Can Lead To Metabolic Disruption

A mitochondrion is an organelle in the body and is popularly known as the powerhouse of the cell. Mitochondria (plural) are the centers where energy production occurs. They supply energy to all cells and the whole body.

BAT and WAT (brown and white adipose tissue)

Adipose tissues are the primary controller of whole-body energy regulation. They store excess energy (in the form of triglycerides) and dissolve the same to provide power to the body in the event of energy scarcity.

There are two types of adipose tissues: brown adipose tissue and white adipose tissue. 

WAT is responsible for storing excess energy, and BAT expends energy at times of energy scarcity. Beige adipocytes (adipose or fat cells) are at a basic level WAT cells. But, at times of extreme duress, beige adipose cells act as BAT and provide the body with extra energy.

Reportedly, mitochondrial malfunction in adipose cells contributes to metabolic disorders, predominantly obesity, and type 2 diabetes. Thus, one of the main causative factors of metabolic disorders is defective cell metabolism - which purportedly is caused by flawed energy production and distribution.

Additionally, a mitochondrial malfunction has adverse effects on the body. 

The Study: Excess Sugar Intake Affects Mitochondrial Integrity and Function

Scientists at the Van Andel Research Institute explored the effects of excess sugar intake on mitochondrial integrity and function.

Scientists used a genetically altered mice model to allow the cells to accept excess sugar intake. Mitochondrial function was then measured using BAT thermogenesis (the process of heat production by brown adipose tissue).

The following were observed in the study:

PUFA or polyunsaturated fatty acids are important for supporting mitochondrial functioning and other biological processes like inflammation, cell to cell communication, and blood pressure regulation.

Saturated fatty acids are what are popularly known as bad fats. This fatty acid isn't nearly as useful or flexible as the PUFA. This disturbs the lipid composition of the mitochondrial membrane, thereby damaging the mitochondrial integrity. 

Restoring normal glucose levels resulted in the balance of the fatty acid levels. This restored the lipid composition as well as the mitochondrial integrity and function.

Additional findings: Cellular stress can trigger early symptoms!

The study found that the cellular changes brought on by a sugar-rich diet may go undetected or may not manifest under normal conditions; upon introduction of cellular stress (changes in cells that are inflicted by environmental stresses like extreme temperatures, exposure to toxins, etc.), these changes may become evident as functional deficiencies. 

In conclusion, excess sugar intake throws off the lipid balance in the body. If the balance is not restored for a while, it can damage our mitochondria, making us more prone to an array of metabolic disorders like type 2 diabetes

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Recommendations

  1. Excess sugar adversely affects insulin activity which is a leading cause of diabetes.
  2. At the cellular level, the pronounced effect of extra sugar is seen in mitochondrial structure and function.
  3. Mitochondrial malfunction, caused due to imbalance in lipid composition, can contribute to a number of metabolic disorders, most commonly, type 2 diabetes.
  4. It can also increase your risk for muscle weakening, improper fat metabolism, seizures, respiratory disorders, and vision and hearing problems.
  5. Cellular stress contributes to apparent symptoms of mitochondrial damage, which would otherwise go undetected.
  6. Cellular stress can be managed by incorporating antioxidants like curcumin and green tea into the diet.
  7. A ketogenic diet, grapefruit consumption, and vitamin E-rich foods can favor healthy mitochondrial functioning. 

Summary

  1. Excess sugar intake adversely affects insulin activity which is a leading cause of diabetes.
  2. At the cellular level, the pronounced effect of extra sugar is seen in mitochondrial structure and function.
  3. Cellular stress contributes to apparent symptoms which would otherwise go undetected.
  4. Cellular stress management can be achieved by incorporating antioxidants like curcumin and green tea in the diet.
  5. Mitochondrial malfunction causes the body to develop a number of disorders which includes metabolic, cardiovascular and neurodegenerative. 
  6. A ketogenic diet, grapefruit consumption, and vitamin E supply can favor healthy mitochondrial functioning.

According to a research study by the University of Exeter Medical School in the United Kingdom, men with hemochromatosis, a common genetic disorder due to iron build-up, are ten times more likely to develop liver cancer. 

What is Hemochromatosis?

Hemochromatosis, also called the iron-overload disease, is a condition where too much iron builds up in the body. Usually, the intestines absorb adequate amounts of iron and excrete the rest.

With hemochromatosis, excess iron is absorbed by the intestines, and the body has no way of getting rid of it. As a result, iron gets built up in joints, the pituitary gland, and organs like the liver, heart, and pancreas.

This gradually results in the shutting down of these organs if hemochromatosis is not treated.

Hemochromatosis is more serious in men. Women may be partially protected as they lose some iron during menstruation and childbirth.

Some common symptoms associated with hemochromatosis include:

  1. Joint pain
  2. Weight loss
  3. Fatigue
  4. Low sex drive
  5. Abdominal pain

The HFE Gene

HFE gene is associated with iron homeostasis. A variant (type) of the HFE gene, called the C282Y (the faulty type), is significantly associated with hereditary hemochromatosis.

According to a study published in the American Journal of Human Genetics, the C282Y variant contributes to 26% variation in ferritin levels among monozygotic twins.

Hemochromatosis and Liver Cancer

With hemochromatosis, the iron build-up is commonly seen in the liver. This enlarges the liver and messes up the liver enzymes. It can result in an increased risk of liver conditions like cirrhosis, fibrosis, and cancer. 

Hepatocellular carcinoma (HCC), a primary form of liver cancer, was the first condition in which hepatic iron overload was shown to predispose to the development of HCC.

According to a study, 8-10% of people with hemochromatosis develop HCC.

The Study

The study was led by the University of Exeter Medical School along with the University of Connecticut, Western University in Ontario, and South Warwickshire NHS Foundation Trust.  

This study focused on men and women with two copies of the faulty HFE gene - C282Y. The data of 2890 people aged 40-70 years were analyzed over a nine-year period.

The following were observed:

  1. 21 out of the 1,294 men with faulty genes developed liver cancer
  2. 14 out of these 21 men died of liver cancer
  3. 10 out of these 21 men were not diagnosed with hemochromatosis by the time they developed liver cancer
  4. **More than 7% of the men** with two faulty genes develop liver cancer by 75 years of age
  5. No increase in liver cancer risk was found in women with the faulty genes

The study insists on the importance of early diagnosis of hemochromatosis in order to avoid health complications and even death.

The NHS advises that “it is important to talk to your GP if you have a parent or sibling with hemochromatosis, even if you don’t have symptoms yourself” to identify your risk. 

The lack of impact on women from the faulty HFE gene variant may suggest that periodic blood donations might play a protective role.

Summary

  1. Hemochromatosis is a condition where your body absorbs too much iron resulting in its build-up in joints and organs. It leads to complications like low sex drive, fatigue, and abdominal pain.
  2. When iron builds up in the liver, it can alter the size of the liver and disturb the liver enzymes. Both these factors contribute to the increased susceptibility to liver diseases like fibrosis, cirrhosis, and cancer.
  3. The HFE gene is associated with the regulation of iron levels in the body. The faulty type of the HFE gene called C282Y increases your risk for hemochromatosis. 
  4. A study by the University of Exeter Medical School revealed that men with two copies of the faulty gene are at an increased risk of developing liver cancer. According to the study, by the age of 75, more than 7% of these men had developed liver cancer. No association was found in women with the faulty genes and liver cancer risk.
  5. Genetic testing, which analyzes your HFE gene type, is a key way to prevent and manage hemochromatosis. The NHS advises people who have a sibling or a close family member with hemochromatosis to talk to their healthcare provider for suitable tests.

Reference:

  1. https://www.sciencecodex.com/liver-cancer-ten-times-more-likely-men-common-genetic-disorder-haemochromatosis-661896
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668053/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995380/
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