Recent research studies have focused on understanding how sugar pathways linked to cancer risks are more direct than was thought. According to Harvard Health, this important macronutrient supplies two subtypes (natural or added) as a source of energy in the form of calories from what we eat and drink. As they pertain to health, it is important whether the source comes from natural fruits and vegetables (fructose, glucose and sucrose), from germinating grains (maltose), or from dairy products (lactose).
When consumed in moderation, sugar provides a quick burst of energy that is broken down into glucose and used by cells for fuel. Glucose also helps to maintain blood sugar levels that are essential for brain function and cognitive processing. Plus, when the body needs more energy during physical activities, sugar can help. This is why it is added to sports drinks to enhance fluid intake and improve hydration; however, overconsumption can have negative effects.
“The most important difference among types of sugar and health risks,” says Dr. Hans Wolf, the founder of WOLFPACC’s Physician Achievement Concept Course, “is whether the source comes naturally from foods or is added during food processing and preparation. Although adding a naturally occurring sweetener like honey is technically classified as added sugar, it is refined sugars processed from natural sources that had its nutrients, fiber and vitamins removed that offer little to no nutritional value.”
Naturally occurring sugars in fruits and vegetables come with beneficial nutrients, but added sugars in processed foods provide less nutritional value and can cause health problems if consumed in excess. So, a key risk factor comes from consuming too much of it from added or refined sugars found in processed foods and sugary drinks. Since the body requires glucose for metabolism, this need is best met with food intake from a balanced diet of fruits, veggies and whole grains.
So, do fruits and veggies have raw sugar?
No, raw sugar is a commercially produced product made of sucrose (e.g. – table sugar) that offers no significant nutritional advantage, so its health effects depend on the amount consumed and not its status as a “raw sugar.” Since raw sugar is classified as an added sugar, it is recommended to consume food and drinks containing raw sugar in moderation. Recent media about consumption of “whole fruits” versus “fruit juices” are based on how the natural fiber that is mostly removed during processing can slow sugar absorption to prevent spikes when left intact. This means whole foods are almost always the healthier food choice as fiber offers health benefits, such as improved regularity and reduced risk of digestive disease.
Sugar’s Journey from Field to Table
Sugar is a natural carbohydrate (macronutrient) that is one of the purest ingredients found in whole foods. In the field, sugar is made through photosynthesis of green plants that turns sunlight into energy. For the most part, sugarcane and sugar beets are the go-to sources that are harvested for sweetening food products and drinks. After all, they have higher sucrose percentages. Nonetheless, both are refined to remove impurities and surrounding plant matter, which leaves a pure form of sucrose.
Although raw sugar is a stage that is specific to sugarcane processing, a purer form of sugar is extracted from both as a similar process that involves purification, evaporation and crystallization to deliver a refined product. Whereas sugarcane is crushed to extract cane juice that is processed into high-impurity raw sugar before being sent to a refinery for purification and then refined into white sugar, the processing of sugar beets skips the raw sugar stage and beet juice is refined through a continuous process.
There are, however, some less-refined beet sugars that resemble raw cane sugar but they are commonly found in Europe. Similar to raw cane sugar that gets its golden-brown color and mild caramel flavor from its residual molasses, less-refined beet sugar is more aromatic and has a more distinct flavor than white beet sugar. These European sugar products come in various forms from light brown crystals to rock sugar for tea, or as a liquid molasses. It should be noted that standard brown sugar is not a beet sugar, which is generally less palatable.
Mechanisms Linking Sugar to Cancer
While sugar itself does not directly cause cancer, pathways link sugar to cancer through several metabolic dysfunctions that it creates. For example, excess consumption of sugar can fuel cancer growth by contributing to obesity that has noted cancer risk. Excess consumption of dietary sugar can also activate pathways that have been linked to breast, colorectal and pancreatic cancers independently. Moreover, cancer cells can support enhanced sugar metabolism for energy that may increase tumor proliferation and progression.
Additionally, too much sugar intake contributes to metabolic dysfunctions like abnormal lipid metabolism and glucose imbalances. Either of these conditions can create an active cellular environment that can promote cancer growth. After all, metabolic reprogramming is a hallmark of cancer, as it helps meet the high energetic demands of tumor cells to produce the macro-molecules required for more rapid proliferation. Without these receptors for growth factors, cancer cells would definitely struggle to survive.
Sugar metabolism refers to the metabolic pathways where sugar molecules are broken down to produce energy (catabolic pathways) or synthesized from smaller molecules (anabolic pathways) to build larger molecules. Collective evidence suggests that sugar’s link to inflammation makes it easier for certain types of cancer to develop and grow. In fact, the effects of high-levels of glucose on cancer cell behavior indicates increased proliferation, invasion and resistance to natural cell death. Public health organizations recommend an added sugar intake of less than 10% of daily calories to help to manage one’s risk.
Important Sugar-Related Metabolic Pathways
Every cell in the human body, including cancer cells, uses glucose from the bloodstream for fuel. In addition, scientists know that cancer cells can hijack sugar metabolism pathways to fuel rapid growth of new cells that promote survival as well as to increase resistance to treatment therapies. Since everyone gets glucose from carbohydrates (and some produced from protein), metabolic pathways can definitely play a role in increased cancer risk. Plus, after stopping smoking, weight control is one of the most important things to do to prevent cancer.
- Glycolysis (catabolic pathway) – Glycolysis is one of the most important processes happening inside your cells right now. This metabolic pathway takes the sugar your body uses for fuel and breaks it down into smaller molecules (pyruvate). It’s a carefully orchestrated sequence of ten enzyme-catalyzed reactions that occur in your cell’s cytoplasm. Glycolysis works tirelessly in nearly every cell as an energy producer and a hub that connects to other essential metabolic and signaling pathways.
- Glycogenesis (anabolic pathway) – Glycogenesis is the body’s smart way of storing glucose (energy) for later use. This anabolic pathway converts glucose into glycogen that is essential to the body’s glucose storage system, primarily in the liver and muscles. Think of it as your body’s energy savings account. When blood glucose levels are high, the liver steps in to store excess glucose as glycogen, which helps to stabilize blood sugar levels by working together seamlessly to ensure your body has energy reserves.
- Gluconeogenesis (synthetic anabolic pathway) – When you haven’t eaten, your body has a clever way of making sure your brain and other vital tissues get the energy they need. This process is called gluconeogenesis. It’s an anabolic pathway, which means it builds up complex molecules from simpler ones. Specifically, it creates new glucose (sugar) from non-carbohydrate sources like lactate, amino acids, and glycerol. This essential function is carefully controlled by hormones such as insulin and glucagon.
- Pentose Phosphate Pathway (alternative pathway) – The PPP is an alternative enzymatic route that branches off from glycolysis. Occurring in the cell’s cytosol, its primary role is to produce essential components for synthesizing nucleotides (the building blocks of DNA and RNA) and lipids. The PPP is also responsible for generating NADPH, a vital reducing agent that helps protect cells from oxidative stress. Because of its support of rapid cell growth, this pathway is often highly active in cancer cells.
- Hexosamine Biosynthetic Pathway (alternative pathway) – The HBP represents a fascinating alternative route for glucose metabolism that plays a crucial role in cancer biology. Unlike the primary glucose pathways, the HBP redirects a small fraction of glucose to produce a vital molecule responsible for modifying proteins throughout the cell. This modification acts like a molecular switch that can turn cellular functions on or off. It influences critical processes that cancer cells depend on for survival.
- Glucose Transporters (protein transport mechanism) – While they’re not metabolic pathways themselves, glucose transporters serve as the essential first step that makes energy production possible. Glucose transporters play a crucial role in how our cells access the fuel they need to function. These specialized proteins act as cellular gatekeepers, controlling the movement of glucose across cell membranes. Cancer cells exploit this system to their advantage, as some overexpress glucose transporter proteins.
- The Warburg Effect (anabolic pathways) – Even when oxygen is available, many cancer cells prefer to get their energy through a process called glycolysis. The Warburg effect involves breaking down glucose into lactate. While this is a less efficient way to produce energy, it’s much faster. Along with the creation of essential cellular building blocks, it helps fuel the fast growth and spread of cancer cells. This distinct metabolic shift is a hallmark of many tumors and is crucial for development and aggressive progression.
- Epigenetic Changes (system of gene regulation) – High glucose levels can trigger epigenetic changes in cancer cells, leading to the prolonged activation of pathways that promote cancer growth. These changes are part of a gene regulation system that controls how genes are expressed without changing the DNA sequence. It’s important to understand that epigenetic changes are not a metabolic pathway for sugar. Instead, these epigenetic modifications regulate the genes that control our metabolic pathways.
- Mevalonate Pathway (cholesterol pathway) – The mevalonate pathway is central to maintaining T-cell development. Dysregulation in these pathways allows cancer cells to acquire cholesterol to support cell proliferation, membrane integrity, homeostasis, immune evasion for cell survival, and to support tumor growth. Statins can effectively block the pathway and impact various cellular processes. This makes the pathway a target for treating conditions like high cholesterol and certain types of cancer.
Studies reviewed by the Division of Cancer Biology at the National Cancer Institute investigated the basic biology behind how fructose indirectly fuels cancer growth as liver cells provide the necessary enzymes to convert fructose into fats called lipids. It is well known that cancer cells consume lots of glucose but less was known about how cancer cells use fructose. Advances in metabolomics have allowed researchers to study how high-fructose corn syrup in mice may cause cancer cells to instruct neighboring cells to provide them with specific nutrients. Obviously human studies are still needed and some cancers use fructose directly.
How Glucose-Fructose Fuels Metastasis
A new study* from the MD Anderson Cancer Center at the University of Texas showed that a common mix of glucose-fructose (i.e. – high fructose corn syrup) found in most sugary drinks and fruit juices can directly fuel metastasis in preclinical models of advanced colorectal cancer. A research team led by Jihye Yun, Ph.D., assistant professor of Genetics, studied how sugary drinks may affect late-stage colorectal cancer. This preclinical provided the first direct evidence that links metastasis to sugar-sweetened drinks.
The sugar mix used by researchers activated an enzyme called SORD that triggered the cholesterol pathway to boost glucose metabolism. Not surprisingly, this is the same pathway that is targeted by statin heart drugs to inhibit normal cholesterol production. This blocking slowed metastasis, which suggests targeting SORD could offer an opportunity to block cancer cell metastasis in the later-stages of colorectal cancer.
Although sugar has long been indirectly linked to increased cancer risk through obesity, this study showed that even a moderate intake of sugary drinks and sweetened fruit juices may also directly impact tumor cell growth in early-stage colorectal cancer, without patient obesity. As always, additional studies are needed but Yun suggested that it may be worthwhile to consider revisions to dietary recommendations for this group.
*NOTE: This study was supported by the National Cancer Institute (NCI), the Pew-Stewart Scholars for Cancer Research program, the Cancer Prevention and Research Institute of Texas, the V Scholar Award, and the Andrew Sabin Family Fellows Award. For a full list of collaborating authors, disclosures and funding sources, see the full paper in Nature Metabolism.
Photo credit Ron Lach
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Medical students today face the challenges created by an infinite number of ongoing research projects being conducted in clinical settings around the world. Certainly, keeping up with the latest findings of how cancer cells can utilize the body’s unique pathways to fuel growth and progression is an important part of one’s studies. Dr. Hans Wolf devoted decades to developing WOLFPACC’s Power 5 Methodology that helps medical students understand how to apply the basic sciences they learned in medical school to the clinical task at hand. Find out today how WOLFPACC can help you apply the knowledge you’ve gained to ensure a successful career in medicine.
