Sugar consumption has been seen as a key risk factor for the development of diabetes since the 1920s.
SWEET SURRENDER: Sugar consumption has been seen as a key risk factor for the development of diabetes since the 1920s. Image Credit: Gulf News / Jay Hilotin

Highlights

  • There’s a need for a change in understanding of negative effects of sugar, fructose in particular.
  • If nothing is done in this regard, the disease burden wrought by diabetes and heart disease will explode, warn expert. 
  • Fructose, a once-beneficial-but-now-deadly type of sugar, is seen as the common link in high blood pressure, insulin resistance, Type 2 Diabetes and obesity. 

Dubai: Sugar has been demonised in recent years. How can such a sweet thing wreak so much havoc in our lives? Fructose, a type of sugar in particular, has been at the receiving end of virulent attacks by diabetes experts. Numerous books had been written about its ill effects, denigrating sugar, and its half-sibling, fructose.

And it’s for a good reason. Fructose has been labelled as the equivalent of a "dietary sleeper terrorist cell" of our times. Fructose intake appears to drive excessive food intake. Here’s why:

Q: What is sugar?

It’s the common name for sweet-tasting, soluble carbohydrates, many of which are used in food and drinks.

“What is there that is not poison? All things are poison and nothing is without poison. Solely the dose determines that a thing is not a poison.”

- Paracelsus, Swiss physician, alchemist, pioneer in the medical revolution of the Renaissance

3 sugar types: What are they?

There are three major types: monosaccharides, disaccharides and polysaccharides.

Sugars broken down org
Image Credit: Gulf News / Jay Hilotin / www.sugar.org
Sugar: 3 types
■ Monosaccharides: Simple sugars include glucose, fructose, and galactose.

■ Disaccharides: Sucrose, a disaccharide composed of glucose and fructose, includes table sugar, granulated sugar, or regular sugar.

■ Polysaccharides (or polycarbohydrates): The most abundant carbohydrate found in food. Examples include “storage” polysaccharides such as starch, glycogen and galactogen and “structural” polysaccharides such as cellulose and chitin.

What is fructose?

It’s a type of simple sugar from fruits. Fructose is one of the three dietary monosaccharides, along with glucose and galactose, absorbed directly into blood during digestion.

Fructose is mainly supplied in the diet — primarily fruits and honey. Eating fruits, or lots of it, especially before the winter — or a drought — was a matter of survival for many species. Fructose is a simple ketonic monosaccharide found in many plants, where it is often bonded to glucose to form the disaccharide sucrose.

Glucose vs Fructose
Image Credit: Gulf News / University of Southern California

What are the benefits of fructose?

Fructose is simply a fat-storage agent that was necessary for the survival of most species, especially humans. It’s credited for being a “key survival factor” in evolution, according to research led by Dr Richard J. Johnson, a nephrologist at the University of Colorado in a 2019 study published in JIM (Journal of Internal Medicine).

Why is fructose associated with the survival of species?

“Fructose metabolism is a common evolutionary pathway of survival associated with climate change, food shortage and droughts,” Dr Johnson and his co-authors wrote. They described fructose as a “survival pathway” used by many species as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability.

What is the main function of fructose?

Simply put, it’s a fat-storage agent. It preferentially shifts the organism towards the storing of fuel (fat, glycogen) that can be used to provide energy and water at a later date — such as long winters/droughts or cataclysmic events that threaten the extinction of a species, researchers explained.

Specifically, what does fructose do?

  • Causes sodium retention
  • Raises blood pressure
  • Helps reduce oxygen demands to aid survival, especially in situations where oxygen availability is low.
  • Shifts energy production from the mitochondria to glycolysis. (ٍSee below)
  • It enhances Vitamin C metabolism.
  • The actions of fructose are driven in part by what’s known as “vasopressin” and the generation of uric acid.
HOW FRUCTOSE SHIFTS ENERGY PRODUCTION
• Mitochondria are membrane-bound cell organelles (singular: mitochondrion) that generate most of the chemical energy needed to power the cell's biochemical reactions. Chemical energy produced by the mitochondria is stored in a small molecule called adenosine triphosphate (ATP).

• Fructose shifts the energy provided in nutrients towards fuel storage (fat, glycogen) and away from energy (ATP) production by downregulating mitochondrial metabolism and the favouring of glycolysis.

How does fructose intake drive excessive food intake?

In a 2017 study published in the journal Advances in Nutrition, Dr Richard Johnson and fellow researchers offered insights into the mechanisms driving obesity and diabetes, specifically focussing on the role of leptin. They found that obesity is associated with leptin resistance that would result in an impaired satiety (sense of being full) response. They also found that obesity is associated with reduced dopamine receptors in the brain (nucleus accumbens) linked to an impaired control related to food intake. 

They pointed out that one potential mechanism for causing fatigue (which leads to less exercise and more sedentary life) relates to mitochondrial function and/or ATP concentrations. Fructose is known to reduce ATP concentrations in the liver, even after oral ingestion of an amount of fructose equivalent to that in a soft drink. Fructose intake also induces oxidative stress that inactivates certain enzyme that then leads to an impairment in fat oxidation, which then reduces ATP concentrations.

Leptin vs Ghrelin
Image Credit: Gulf News / hormone.org
LEPTIN: THE "SATIETY HORMONE"
• Leptin is a hormone made by small intestine cells that helps regulate energy balance by inhibiting hunger. That's why it's also known as the "satiety hormone". making it directly connected to body fat and obesity. This hormone released from the fat cells located in adipose tissues, which sends signals to the hypothalamus in the brain.

• Leptin helps regulate and alter long-term food intake and energy expenditure, not just from one meal to the next. The primary function of leptin is to help the body maintain its weight.

• Because it comes from fat cells, leptin amounts are directly connected to an individual’s amount of body fat. If the individual adds body fat, leptin levels will increase. If an individual lowers body fat percentages, the leptin will decrease as well.

• It helps inhibit hunger and regulate energy balance, so the body does not trigger hunger responses when it does not need energy.

• However, when levels of the hormone fall, which happens when an individual loses weight, the lower levels can trigger huge increases in appetite and food cravings. This, in turn, can make weight loss more difficult.

What’s the role of fructose in the suvival of humans and other species?

Researchers point out that mutations have occurred during at least two periods of mass extinction — that enhanced the activity of fructose to generate fat.

So from the point of view of paleontology, fructose is the agent that enhances fat generation, which was useful during periods of cataclysms such as during the Cretaceous– Paleogene extinction (65 million years ago) and the Middle Miocene disruption (12–14 million years ago), which led to the extinction of many species. These properties of fructose, researchers argued, likely helped survival in the setting of extreme dehydration or salt deprivation.

Sugary drinks
High-fructose corn syrup (HFCS) is also known as glucose-fructose, isoglucose and glucose-fructose syrup. It is a sweetener made from corn starch and is commonly used in soft drinks.
What is adenosine triphosphate (ATP)?
• Adenosine triphosphate (ATP) is the energy-carrying molecule found in the cells of all living things.

• A compound consisting of an adenosine molecule bonded to three phosphate groups, and is present in all living tissue. The breakage of one phosphate linkage (to form adenosine diphosphate, ADP ) provides energy for physiological processes such as muscular contraction.

In today’s world, is fructose intake necessary?

No. The long and short of fructose is that it helps the body store fat for a food-less winter or drought. In prehistoric times, when there's no industrial food production, having no source of fructose is an existential threat. But in today's word, when sugar is widely available and you have supply of fruits all year round (watermellon from Hunduras, Iran, China at different times of the year!) thank to transcontinental travel, this is problematic. And this is a growing health issue both in rich and developing countries. That's why many governments, including the UAE, are now implementing a "sugar tax".

Why? fructose intake is seen as the biggest driver for the global diabetes bulge, now considered a "silent pandemic".

Glycolysis vs Glyconeogenesis
Sugar is so important in the normal function of our body that when we don't get it, the body generates it.

• Glycolysis the breakdown of a carbohydrate (such as glucose) by way of phosphate derivatives with the production of pyruvic or lactic acid and energy stored in high-energy phosphate bonds of ATP.

• Glyconeogenesis: Turning fats in to glucose. It's the process of fat-burning, via the synthesis of sugars (such as glucose and glycogen) from substances other than sugars. In short, it's the production in our body of carbohydrates (glycogen), from amino acids, fats, and other non-carbohydrates.

What are the ill effects of fructose, or excessive fructose intake?

Fructose overload (from softdrinks, for example) leads to mechanisms that are better understood by today's medical science. It's a key factor in a sort of slow-release horror movie that arises from fructose overdose. Today, fructose plays a big role in the high incidence of the double whammy of diabetes and obesity. If nothing is done, say experts, and there’s no change in understanding of negative effects of sugar — fructose in particular — the disease burden wrought by diabetes and heart disease will explode, warns Dr Rick Johnson, author of The Sugar Fix: The High-Fructose Fallout That Is Making You Fat and Sick.

We’ve actually done trials in patients with low-fructose diet, with or without natural fruits supplements. If you took a patient and restrict all fructose, except fruits, they tend to do OK. They did just as well as those on low-fructose diet alone. Some fruits like kiwi, lime and lemon have almost no fructose. They’re totally safe. Berries have so many good things in it, you can eat a big bowl, no problem. Blueberries, raspberries, strawberries, all other berries in general, are all very good.”

- Dr Rick Johnson, author of The "Sugar Fix: The High-Fructose Fallout That Is Making You Fat and Sick"

Do fruits have anything good to offer?

Rick Johnson, M. D., author of The "Sugar Fix: The High-Fructose Fallout That Is Making You Fat and Sick", states: “There are so many good things in fruit: Vitamin C, flavonoids, epicatechin, potassium — which fight the effects of fructose. But if you eat a huge amount of fruit and get all that fructose, it will start to overwhelm the good things in fruit. Pineapple and grapes have a fair amount of fructose. What I would recommend is try not to eat too many fruits at one time.”

WHEN DOES GLYCONEOGENESIS OCCUR?
When does gluconeogenesis occur? It occurs during starvation and after a meal high in fat and protein without carbohydrate. Gluconeogenesis and insulin resistance occur to raise serum glucose levels to provide fuel to the brain.
NAT-OBESE-1-(Read-Only)
SILENT EPIDEMIC: Numerous studies show that fructose-containing added sugars, such as sucrose and high-fructose corn syrup, have been shown to be involved in the current epidemics of obesity and diabetes.

What are the main dietary sources of fructose?

The highest dietary sources of fructose, besides pure crystalline fructose:

  • Pure crystalline fructose
  • Foods containing table sugar (sucrose)
  • High-fructose corn syrup (common used in soft drinks)
  • Agave nectar
  • Honey
  • Molasses
  • Maple syrup
  • Fruit and fruit juices (these have the highest percentage of fructose, including fructose in sucrose per serving).

What are the harmful effects of excess fructose?

  • Impairs the composition of your blood lipids.
  • Raises the levels of VLDL cholesterol, leading to fat accumulation around the organs and potentially heart disease.
  • Increases blood levels of uric acid, leading to gout and high blood pressure

What is non-alcoholic fatty liver disease (NAFLD)?

It is the general term for a range of conditions caused by a build-up of fat in the liver. It's usually seen in people who are overweight or obese. In clinical terms, it is defined as the excessive accumulation of triglycerides (>5%) in the hepatocytes (cells in the liver) in the absence of significant alcohol consumption.

How is NAFLD diagnosed?

NAFLD is often diagnosed after a blood test called a liver function test produces an abnormal result. Other liver conditions, such as hepatitis, must be ruled out.

There are three major types of tests are used to diagnose NAFLD:

  1. Blood tests such as liver function tests that measure inflammation of the liver
  2. Tests to visualise the appearance of the liver, such as ultrasound, computed tomographic (CT) scan, and magnetic resonance imaging (MRI)
  3. Newer tests that quantify the amount of fat in the liver, such as transient elastography (ultrasound-based test that measures how stiff the liver is).

Blood tests do not always pick up NAFLD. When the liver has a great deal of fat, ultrasound-based tests may not be very reliable for diagnosing more advanced liver disease (NASH and liver fibrosis).

If there is a suspicion of advanced liver disease or some other cause of liver problems, a liver biopsy may be recommended, in which a small piece of liver is obtained using a needle inserted through the skin into the liver, according to the journal JAMA.

What is the recommended fructose limit for people with NAFLD?

Some experts recommend only up to 10 grams of fructose a day — and only in the form of whole fruit — for people with NAFLD.

Sugar
“High-fructose corn syrup and sucrose are exactly the same,” according to Dr Robert Lustig, a University of California in San Francisco (UCSF) paediatric neuroendocrinologist. “They’re equally bad. They’re both poison in high doses.” r Lustig said fructose is just as bad as alcohol in causing fat storage in the liver — and in a leading cause of non-alcoholic fatty liver disease.

'Sugar is poison': Did someone actually say that?

Yes, fructose in particular. In Sugar: The Bitter Truth, Dr Robert Lustig, a University of California in San Francisco (UCSF) paediatric neuroendocrinologist, made controversial claims about sugar. His Youtube video has been viewed more than 12 million times. One idea he advances is this: Calorie for calorie, sugar causes more insulin resistance in the liver than other edibles.

He explained thus: Each sucrose molecule consists of one molecule of fructose joined to one molecule of glucose. The two are quickly split apart in the gut. High-fructose corn syrup (HFCS) is a less expensive mixture of glucose and fructose. However, Dr Lustig said, there is no use hairsplitting the difference.

High-fructose corn syrup and sucrose are exactly the same. They’re equally bad. They’re both poison in high doses.

- Dr Robert Lustig, paediatric neuroendocrinologist, University of California in San Francisco (UCSF) ("Sugar: The Bitter Truth")

“High-fructose corn syrup and sucrose are exactly the same,” Lustig argues. “They’re equally bad. They’re both poison in high doses.” Here’s an even more controversial claim: Dr Lustig said fructose is just as bad as alcohol in causing fat storage in the liver — and in a leading cause of non-alcoholic fatty liver disease.

Is it an indictment of fructose?

In the 1990s, Dr Lustig worked with children diagnosed with “hypothalamic obesity”, a disorder that can occur after brain tumour surgery. He observed that the children were making more insulin than was necessary for normal energy storage in fat cells. He then hypothesised the kids were not receiving signals from leptin — which helps send a message that the appetite has been sated. He tried the same treatment with obese adults, and found that a subset responded in the same way as the children with hypothalamic obesity.

It's these groundbreaking studies that led to the development ofof his controversial ideas about metabolism and biological feedback in weight control. One not-yet-popular idea is that, calorie for calorie, sugar causes more insulin resistance in the liver than other edibles. The pancreas then has to release more insulin to satisfy the liver’s needs. High insulin levels, in turn, interfere with the brain’s receipt of signals from the leptin hormone, which is secreted by fat cells, Lustig believes.

How does eating affect insulin and leptin generation?

It’s a fact that eating stimulates secretion of insulin and leptin. The conventional view holds that insulin, like leptin, feeds back in the brain to limit food intake, Lustig explains. Now Lustig does not believe chronically elevated insulin levels feed back negatively to curb eating.

What about dried fruits?

Dried fruits have the fructose of fruits without the good things in it. A lot of the good things in natural fruits are lost. “It’s like pure fructose,” said Dr Rick Johnson, professor of nephrology at the University of Colorado, and author of “The Sugar Fix: The High-Fructose Fallout That Is Making You Fat and Sick”.

Insulin vs leptin
Dr Lustig now believes that chronically elevated insulin blocks leptin’s “negative feedback” signal. “Most people think insulin does the same thing as leptin,” he declares. “I think it does just the opposite.”

Dr Lustig hypothesised that fructose generates greater insulin resistance than other foodstuffs. Specifically, he said that fructose calories fail to blunt appetite in the same way as other
Lustig’s conclusion: The children’s brains were fooled into thinking that they were starving. His solution was to administer a drug called octreotide, known to block insulin release. The result: Insulin levels fell. The children ate less, lost weight, spontaneously became more active and improved their quality of life.

*Lustig’s book Fat Chance: Beating the Odds Against Sugar, Processed Food, Obesity, and Disease has received rave reviews on Amazon.

*Lustig’s book Fat Chance: Beating the Odds Against Sugar, Processed Food, Obesity, and Disease has received rave reviews on Amazon.

LOOKING AHEAD

Fructose may be taken but only in small amounts, say experts like Lustig. They believe that excessive fructose intake due to the ready availability of refined sugar and high-fructose corn syrup is what drives the “burden” of lifestyle diseases — obesity, diabetes and high blood pressure. Leading researchers argue that people would stay clear of fructose.

(Editing by Shyam Krishna, Senior Associate Editor)