This is an abbreviation of unit 10 from the Advanced Equine Nutrition course. The complete text, a video, and quiz questions are available with The Horse’s Advocate membership. You can also purchase them separately. Note: Passing the Basic Equine Nutrition Course is required before starting the Advanced Course.

Unit 10 – Fructose And Its Master Effect On Survival

This chapter unveils the captivating world of fructose, a sugar with a unique composition. Like its counterpart glucose, fructose is composed of 6 carbons, 12 hydrogens, and 6 oxygens. However, the arrangement of these elements is distinct, much like two similar keys that won’t unlock each other’s locks. This unique structure sets fructose apart and forms the basis of its enthralling effects on survival and cell metabolism.

While most people associate fructose with fruit sweetness, its primary role is as a signal for animals, including horses, to prepare for the hard times of winter. As the fruit ripens, it produces fructose from glucose, enhancing its taste and attracting animals to eat the sweet seeds of the plants, which aid seed dispersal. This unique function of fructose ensures the survival of plants by spreading their seeds, and it promotes fat storage for animals in winter.

The intriguing aspect of ripening fruit is that Vitamin C concentration decreases and fructose increases; high levels of this vitamin reduce the effects of uric acid, the metabolite of fructose. More on this later.

Nectar, too, is rich in fructose, luring birds and insects to assist in seed dispersal. Hummingbirds eat so much nectar daily that they become very insulin-resistant and develop fatty livers at the end of one day. Their bodies recover by morning (an overnight fast) with normal insulin response and liver composition.

This chapter delves into the intricate and fascinating mechanisms behind fructose metabolism, underscoring the vital role of this sugar in horses’ survival and the potential detriment when it goes awry.

Why Fructose Is Different Than Glucose

When traveling in the blood, fructose does not damage proteins; therefore, unlike glucose, fructose does not need the escort hormone insulin.

Glucose is mainly broken down in the intestinal enterocytes into lactate, which can freely move through the body by blood. Lactate is the primary fuel for all cells in the body. Any remaining glucose is bound to insulin to protect the body from damage, then transported to muscle cells for energy production and storage as glycogen or to the liver for storage as glycogen and body, visceral, or organ fat. Excess lactate can be shared with neighboring cells or returned to the liver to become glucose again.

Fructose also breaks down in the enterocytes and all other cells to become uric acid using the enzyme fructokinase. It also flows mainly to the liver and brain; it can be used in muscles but is uncommon. However, because fructose concentrates in these areas, it is associated with fatty liver disease and causes depletion of energy in the brain. In the gut, an unknown connection with the brain causes the animal to consume more fructose; however, there are findings in the brain that are similar between sugar addiction and alcohol and heroin addictions in humans and lab animals.

Excess fructose metabolism results in obesity and metabolic syndrome due to decreased efficiency in cell metabolism. When fructokinase metabolizes fructose in the cell, it bypasses the ATP regulatory steps found with glucose metabolism, causing the depletion of ATP to be well below the minimum set point of 90%. The cell runs low on energy and can no longer metabolize substrates. The low amount of cellular ATP signals the cell to convert all glucose into glycogen or fat for later use; fructose causes increased body fat through energy depletion because it cannot afford to convert ATP to ADP.

The Polyol Pathway

Animals can make fructose. Another pathway in the body’s infinite mechanisms is the Polyol Pathway, also called the Sorbitol Pathway, because sorbitol is an intermediate product. While this pathway is present in humans and many other animals, it has not been closely examined in horses. This pathway explains why animals that don’t eat fruit, such as desert animals and aquatic mammals, become very fat. Further, humans with diabetes have excess blood glucose that triggers the formation of sorbitol through this process. In humans, the eye’s lens, the retina, the kidneys, and the specialized cells that make the myelin covering the nerves (Schwann Cells) cannot convert sorbitol into fructose. Because of this, sorbitol accumulates in these areas, causing cataracts, retinopathy, nephropathy, and neuropathy in diabetics. Are there areas like these in horses? For example, what about the lamina of the hooves?

Why Commercial Horse Feeds Are Bad For Horses

The glycemic index measures a food ingredient’s ability to become glucose. With glucose set at a score of 100, all other food ingredients compare themselves to that score. High-glycemic foods are those with a score of 70 or higher. All grains score above 70 and, therefore, promote the polyol pathway. Feeding grains plus hay high in glucose or growing pasture causes more fructose production through the Polyol Pathway. Could it be worse?

Key Points:

1. Fructose has the same chemical formula as glucose, but the elements are arranged differently.
2. Fructose is responsible for the sweet taste of food. It helps plants spread their seeds while adding body fat to those eating it for warmth in winter.
3. Energy is created when an element is lost from ATP, NAD, or FAD. This loss creates a charge that can be stored in the ETC.
4. Glucose undergoes glycolysis in the cell’s cytoplasm, yielding 2 ATP, 2 NADH, and 2 lactate molecules.
5. Lactate, fat, and ketogenic amino acids enter the Krebs Cycle, yielding 36 ATP.
6. Glucose will become 2 lactate molecules, glycogen, or body fat.
7. ATP, like money, has a set minimum level for investment. This regulation prevents a permanent depletion of energy and cell death.
8. Sleep helps to restore ATP levels when little glucose enters the cells.
9. Fructose moves freely in the blood without needing insulin or any other escort.
10. Fructose reduces ATP to below their minimal levels, decreasing the available energy to maintain energy production efficiency.
11. Fructose metabolism depletes ATP. It does this by not returning ADP to ATP. Instead, it further breaks down ADP to AMP, which becomes uric acid.
12. High uric acid levels in the blood promote fat production (lipogenesis). It decreases BMR and increases oxidative stress. It also increases thirst and salt retention, which leads to higher blood pressure. Furthermore, it increases low-grade inflammation and systemic insulin resistance. Lastly, it decreases mitochondrial function.
13. All of the effects of uric acid prepare horses for the upcoming winter. They are designed for temporary, seasonal use.
14. The Polyol Pathway (the Sorbitol Pathway) converts glucose into fructose, with sorbitol as an intermediate molecule.
15. The Polyol Pathway makes fructose from glucose under certain conditions. These include dehydration and low oxygen. It also happens with abundant high-glycemic foods that raise blood glucose. Additionally, umami foods high in AMP, IMP (inositol adenosine phosphate), and Glutamate contribute to this.
16. All grains and molasses are high-glycemic foods, triggering the Polyol Pathway. They have inflammatory ingredients, adding to the inflammation from uric acid.
17. Added salt promotes dehydration, triggering the Polyol Pathway. 
18. Many horse feeds have yeast added, triggering the Polyol Pathway.
19. Keeping horses in their stalls decreases oxygen to cells (lack of exercise), possibly triggering the Polyol Pathway.