Not all sugars are created equal. A new study published by the scientists from the Washington University School of Medicine (WUSM) reports that trehalose, a natural sugar that can be found in mushrooms, can boost macrophages, the machinery that the immune system uses to cleanup cellular debris in the atherosclerotic plague, and therefore reduces the progression atherosclerosis.

Atherosclerosis is a disease in which plaque builds up inside your blood vessel arteries. Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. Over time, plaque hardens and narrows the arteries. This limits the flow of oxygen-rich blood to vital organs such as heart and brain. Atherosclerosis can lead to serious problems, including heart attack, stroke, or even death. In the United States and most other developed countries, atherosclerosis is the leading cause of illness and death.

Trehalose is a sugar consisting of two linked glucose molecules. In nature, trehalose can be found in animals, plants, and microorganisms. In animals, trehalose is prevalent in shrimp. Trehalose is nutritionally equivalent to glucose, because it is rapidly broken down into glucose by the enzyme trehalase, which is present in the intestine.

The WUSM researchers focused on the ability of trehalose to increase the amount of organelles inside specialized “housekeeping” cells known as macrophages. These white blood cells digest unwanted cellular material in the body and the organelles (i.e. cleaning tools) they contain help them to do the work. However, in atherosclerosis, when macrophages try to fix damage to the artery by cleaning up the area, they often get overwhelmed by the plaques’ inflammatory nature and their housekeeping process gets gummed up. This unfortunately triggers the immune system to send more immune cells to try to clean up the mess, which exacerbates the problem − a soup starts building up with dying cells and debris and the plaque grows.

In this study, when the researchers injected mice predisposed to atherosclerosis with trehalose, they saw an approximate 30 percent reduction in the size of plaques in the rodents’ arteries. Further research shows that trehalose works by activating a molecule called TFEB. This molecule activates genes in macrophage leading to the creation of the additional organelles, effectively turning the macrophages into “super-macrophages.” Therefore, trehalose is not just enhancing the housekeeping tools that are already there; it triggers the cell to make new tools. With its increased ability to clean up unwanted material in the arteries, the super-macrophages could reduce the built-up of the plagues and therefore slow down the progression of atherosclerosis. Knowing how trehalose works, the researchers are also hopeful that trehalose could help fight other conditions including type 2 diabetes and fatty liver disease.

Unfortunately, the study showed that trehalose only worked when it was given as an injection. When it is taken orally, digestive enzymes break it apart and therefore shut down its TFEB-activating property.

Thanks for reading.

Dr. Connie Wan

Journal Reference: Sergin, I.; Ranani, B. et al., Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis, Nature Communications 8, Article number: 15750 (2017), doi:10.1038/ncomms15750.

Source: Informed Nutrition

Mannitol is a sugar alcohol produced by fungi, bacteria, and algae. According to a report published in the Journal of Biological Chemistry, researchers from Tel Aviv University have found that mannitol prevents “bad” clumps of the protein, α-synuclein, from forming in the brain — a process that is characteristic of Parkinson’s disease.

After identifying the structural characteristics that facilitate the development of clumps of α-synuclein, the researchers began to hunt for a compound that could inhibit the proteins’ ability to bind together. In the lab, they found that mannitol was among the most effective agents in preventing aggregation of the protein in test tubes.

To test the capabilities of mannitol in the living brain, the researchers turned to transgenic fruit flies engineered to carry the human gene for α-synuclein. To study fly movement, they used a test called the “climbing assay,” in which the ability of flies to climb the walls of a test tube indicates their locomotive capability. In the initial experimental period, 72 percent of normal flies were able to climb up the test tube, compared to only 38 percent of the genetically-altered flies.

The researchers then added mannitol to the food of the genetically-altered flies for a period of 27 days and repeated the experiment. This time, 70 percent of the mutated flies could climb up the test tube. In addition, the researchers observed a 70 percent reduction in aggregates of α-synuclein in mutated flies that had been fed mannitol, compared to those that had not.

These findings were confirmed by a second study that measured the impact of mannitol on mice engineered to produce human α-synuclein. After four months, the researchers found that the mice injected with mannitol also showed a dramatic reduction of α-synuclein in the brain.

Despite the promising animal studies, mannitol’s effectiveness as a potential treatment for Parkinson’s disease needs more research. However, mannitol is a common component of sugar-free gummy products. The sugar is also approved by the FDA as a diuretic to flush out excess fluids and used during surgery as a substance that opens the blood/brain barrier to ease the passage of other drugs. Therefore, the compound has an excellent safety profile. For Parkinson’s patients, mannitol probably is worth trying as a supplement.

Thanks for reading.

Dr. Connie Wan

Journal Reference: Shaltiel-Karyo, M. Frenkel-Pinter, E. Rockenstein, C. Patrick, M. Levy-Sakin, A. Schiller, N. Egoz-Matia, E. Masliah, D. Segal, E. Gazit. A Blood-Brain Barrier (BBB) Disrupter Is Also a Potent  -Synuclein ( -syn) Aggregation Inhibitor: A NOVEL DUAL MECHANISM OF MANNITOL FOR THE TREATMENT OF PARKINSON DISEASE (PD). Journal of Biological Chemistry, 2013; 288 (24): 17579 DOI: 10.1074/jbc.M112.434787

Source: Informed Nutrition

A range of diseases — from diabetes to cardiovascular disease, and from Alzheimer’s disease to attention deficit hyperactivity disorder — are linked to changes to genes in the brain. A study by UCLA scientists has found that hundreds of those brain genes can be damaged by fructose, a sugar that’s common in the Western diet. This means that, by altering genes in the brain, fructose could affect the occurrence of these diseases. However, the researchers discovered good news as well: the omega-3 fatty acid, docosahexaenoic acid (DHA), seems to reverse the harmful changes produced by fructose.

DHA occurs naturally in the membranes of our brain cells, but not in a large enough quantity to help fight diseases. Human brain and the body are deficient in the machinery to make DHA; it has to come through our diet. DHA strengthens synapses in the brain and enhances learning and memory. It is abundant in wild salmon and, to a lesser extent, in other fish and fish oil, as well as walnuts, flaxseed, and fruits and vegetables.

To test the effects of fructose and DHA, the researchers trained rats to escape from a maze, and then randomly divided the animals into three groups. Then, for six weeks, one group of rats drank water with an amount of fructose that would be roughly equivalent to a person drinking a liter of soda per day. The second group was given fructose water and a diet rich in DHA. The third received water without fructose and no DHA.

After the six weeks, the rats were put through the maze again. The animals that had been given only the fructose navigated the maze about half as fast than the rats that drank only water — indicating that the fructose diet had impaired their memory. The rats that had been given fructose and DHA, however, showed very similar results to those that only drank water — which strongly suggests that the DHA eliminated fructose’s harmful effects.

Other tests on the rats revealed more major differences: The rats receiving a high-fructose diet had much higher blood glucose, triglycerides and insulin levels than the other two groups. Those results are significant because in humans, elevated glucose, triglycerides and insulin are linked to obesity, diabetes and many other diseases.

The research team sequenced more than 20,000 genes in the rats’ brains, and identified more than 700 genes in the hypothalamus (the brain’s major metabolic control center) and more than 200 genes in the hippocampus (which helps regulate learning and memory) that were altered by the fructose. The altered genes they identified, the vast majority of which are comparable to genes in humans, are among those that interact to regulate metabolism, cell communication and inflammation. Among the conditions that can be caused by alterations to those genes are Parkinson’s disease, depression, bipolar disorder, and other brain diseases.

The research also uncovered new details about the mechanism fructose uses to disrupt genes. The scientists found that fructose removes or adds a biochemical group to cytosine, one of the four nucleotides that make up DNA. This type of modification plays a critical role in turning genes “on” or “off.”

Americans get most of their fructose in foods that are sweetened with high-fructose corn syrup such as soda drinks. Next time, when top off your cup at the soda fountain, remember to take your omega-3 supplement with the drink.

Thanks for reading.

Dr. Connie Wan

Journal Reference:

Meng, QY et al. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders. EBioMedicine, 2016; DOI: 10.1016/j.ebiom.2016.04.008

“Sugar” is essential for life on Earth. It can be found in nearly all food sources. What is “sugar”, where does it come from, and (this may seem like a strange question to ask) what is it used for. This blog post attempts to answer these questions.

What is sugar

The term “sugar” is generic. Most of us are familiar with granulated table sugar. However, it turns out that table sugar is only one type among many. Chemistry-wise, table sugar is the called “sucrose” with the chemical structure shown below.

There are many different types of sugars in addition to table sugar. Another sugar that many would be familiar with is lactose, or milk sugar. It has the following chemical structure:

Both sucrose and lactose molecules have two ring systems that are linked together by a bond that looks like  or .  The two rings in the sucrose (table sugar) molecule are glucose and fructose, while the rings in the lactose (milk sugar) molecule are glucose and galactose. Therefore, sucrose comes from the chemical reaction that links one glucose molecule with one fructose molecule and lactose comes from the chemical reaction that links one glucose molecule with one galactose molecule.  The chemical structures for glucose, fructose and lactose are shown below.

So, if sucrose comes from glucose and fructose and lactose comes from glucose and galactose, where do glucose, fructose, and galactose come from?

Where does sugar come from?

The source of sugar is one of the most elegant stories that the universe has to offer. Our planet Earth orbits the sun, also known as Sol, in a position within habitable zone that allows for liquid water, two hydrogen atoms to one oxygen atom or H₂O, to exist on the surface as shown below.

The fact that liquid water persists on Earth is very important to answering the question as to where sugar comes from. Sucrose, lactose, glucose, galactose, fructose all contain carbon, oxygen and hydrogen. The oxygen and hydrogen come from water and the carbon comes from carbon dioxide which is in the atmosphere of Earth. Thus, sugar is water forming a chemical compound with carbon; hence the term “carbohydrates”. Sugars are carbohydrates.

How is sugar formed?

Sugar comes from plant life on Earth. Plants have a molecule in them called chlorophyll that makes them green and sometimes purple, or even black.

Chlorophyll strongly absorbs photons in the blue and red regions of the electromagnetic spectrum. Photons have energy associated with them. The energy from the sun is absorbed by chlorophyll and is used to combine carbon dioxide and water to make carbohydrates (sugar) according to the following, simplified equation.

Thus, from the sun, carbon dioxide, water, Earth’s orbital position around the sun, and the chlorophyll molecule, we get two things we need for our survival: glucose (food for us to eat) and oxygen for us to breath; this is photosynthesis.

Nature’s Batteries

Think of photosynthesis as nature’s original solar cell, and sugars as nature’s molecular batteries. Many different sugars are formed from photosynthesis. For example, there are trioses (sugar molecules having three carbons, such as glyceryl aldehyde and 1,3-dihydroxyacetone), tetroses (sugar molcules having four carbons, such as erythrose and xylulose), pentoses (sugar molecules having five carbons, such as ribose), and hexoses (sugar molecules having six carbons, such as fructose, mannose, glucose). All of these are simple sugars or monosaccharides, meaning they are foundational sugars that cannot be broken down further to yield an even simpler sugar. There are many different monosaccharide sugar molecules out there, but the one most important for animal life is glucose as it is used for energy to power the biological systems. Other hexoses, such as mannose or fructose, are converted to glucose (by the liver), and the resulting glucose is then used for energy.

Plants use glucose for energy just as we use glucose for energy. However, plants typically produce excess glucose and other monosaccharides. Through further reactions, plants store the energy by combining monosaccharides into larger entities. One such entity is sucrose (table sugar).  As described earlier, sucrose is made of one glucose molecule and one fructose molecule both of which are simple sugars. Thus, sucrose is a disaccharide or a sugar molecule comprised of two simple sugars. However, plants do not stop there, they can make even bigger molecules with simple sugars.

Big molecules of glucose

All plant matter on earth is derived from sugars. In addition to mono- and disaccharides, there are even larger sugar structures called polysaccharides. Glucose performs an internal cyclization as shown below to yield a ring structure, α-D-glucopyranose or β-D-glucopyranose. Roughly one-third of glucose becomes the alpha form and two-thirds becomes the beta. The alpha and beta forms of the pyranose forms of glucose have different uses by the plant.

Plant life takes the alpha and beta ring forms of glucose and makes large molecules out of them by linking them together using  and  type structures (bonds). Macromolecules of several million in molecular weight can be formed. There are monosaccharides for simple sugars, disaccharides for sugars that link two simple sugars together, and there are polysaccharides for very large macromolecular sugars.

Macromolecules consisting a-ringed structure of glucose units are called the sugars amylose and amylopectin, which constitute starch.  Starch is another form of energy storage for the plant. The plant (and animal life) can use the starch as a food source later on. Our bodies produce amylase, an enzyme which catalyzes the decomposition of amylose into glucose units for us to use as energy.

Macromolecules consisting of b-ringed glucose units is called cellulose. Cellulose constitutes the cell walls of plants. Wood is composite of cellulose and lignin. Cellulose supports the trees against Earth’s gravity. Cellulose is a very strong structural material because the chains strongly interact with each other.  However, we lack the enzyme to decompose cellulose. Hence, we cannot use cellulose as a food source.

Summary

This article provides a brief description of what is “sugar”.  Sugar is much more than just table sugar (sucrose), but certainly table sugar is an important sugar for us. The word sugar encompasses a very wide range of molecules.  Sugars are the photosynthesis products of plant chlorophyll combining energy from the sun, water and carbon dioxide.  Photosynthesis yields a variety of simple sugars including glucose, an energy source for our bodies. Glucose and the other simple sugars combine to make more complex disaccharides such as sucrose (table sugar) and polysaccharides such as starch and cellulose all of which fall under the name “sugar.”

Thanks for reading.

Dr. Brenden Carlson

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