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Vitamin D prevented brain damage by High Fructose corn syrup (in rats) – Feb 2024

Protective effect of vitamin D on learning and memory impairment in rats induced by high fructose corn syrup

Behavioural Brain Research Vol 459, 29 Feb 2024, https://doi.org/10.1016/j.bbr.2023.114763 behind a $31 paywall
Cahide Aslan a 1, Rahime Aslankoc a, Ozlem Ozmen b, Buse Nur Sülük a, Oguzhan Kavrık a, Nurhan Gumral a

In our study, we aimed to investigate the negative effects of the prefrontal cortex (PFC)-associated impairment of cholinergic activity on memory and learning caused by high fructose corn syrup (HFCS) and the protective role of vitamin D in adolescent rats.

Twenty-four animals were divided into three groups as control, HFCS group (11 % HFCS-55 solution, ad libitum) and HFCS+ Vit D (42 μg/kg/day). Elevated Plus Maze (EPM), Forced Swim Test (FST), and Morris Water Maze (MWM, performed from day 23) tests were applied to all animals. Fluid intake consumption of the rats was measured daily, weight gain and blood glucose were measured weekly. After 31 days of treatment, the rats were sacrificed and PFC tissue was removed for biochemical, histopathological and immunohistochemical analyses.

In HFCS group, fluid consumption, blood glucose, malondialdehyde (MDA) levels, degenerative neuron count and choline acetyltransferase (ChAT) expression were significantly increased; superoxide dismutase (SOD), catalase (CAT) enzyme activity and brain-derived neurotrophic factor (BDNF) expression were significantly decreased. In addition, the time spent in the enclosed arm in EPM was increased, the immobility time in FST was, and the time spent in the target quadrant in MWM was significantly decreased. Vitamin D treatment reversed all these parameters. In conclusion, HFCS caused an increase in the number of degenerative neurons in the PFC, disrupted cholinergic activity and negatively affected learning-memory functions. Vitamin D, decreased the number of degenerative neurons, increased cholinergic activity and positively affected learning and memory performance.

Brief Synopsis
In this study, prefrontal cortex damage was investigated in adolescent rats fed high fructose corn syrup.
The effect of vitamin D on prefrontal cortex damage was evaluated.

The prefrontal cortex (PFC) is a highly complex structure of the brain that integrates processed sensory information from cortical and subcortical structures to facilitate memory, perception, and complex actions [1]. In this respect, PFC damage has been shown to be associated with episodic memory impairments, thinking, behavior and personality changes, especially in the early stages [2]. Many psychiatric and neurologic conditions are related to deficits in cognitive control and dysfunction in PFC-related circuits [3]. It is known that cholinergic neurotransmission is involved in such processes as memory and other cognitive functions. It is also known that cholinergic neurons are closely associated with learning-memory processes in the cortex and hippocampal area [4]. With the development from childhood to adulthood, prefrontal areas undergo major changes as a result of a decrease in gray matter, increase in white matter, and myelination processes. During adolescence, PFC becomes more strongly linked to sensory and subcortical brain areas. It has been reported that different experiences gained during this period may profoundly affect the development of prefrontal areas and contribute to the improvement of connectivity [5].

High fructose corn syrup (HFCS) is a corn-derived ingredient used as a sugar substitute in various food products such as soft drinks, fast food and other processed foods. HFCS, cane sugar, and honey have similar chemical structure and caloric values. Nowadays, HFCS has become a highly preferred sweetener due to its low cost, liquid form, intense sweet taste and preservative properties. [6].

A diet containing HFCS leads to adverse health effects such as

  • diabetes [7],
  • cardiovascular diseases [8],
  • fatty liver disease and
  • metabolic syndrome. It is also believed to
  • contribute to the spread of obesity [7].

In addition, in a study conducted on adolescents, it was pointed out that HFCS may cause detrimental health outcomes such as elevated plasma triglycerides and insulin resistance [9]. It has also been shown to cause depression-like behavioral changes in adolescent rats with increased oxidative stress and physiological changes [10].

Oxidative stress has been associated with the onset or progression of various neurodegenerative disorders. In addition, oxidative stress also triggers an inflammatory response [11]. HFCS diet is linked to inflammation and oxidative stress [12]. Excessive consumption of HFCS and sugar during adolescence, a critical period of development, is associated with cognitive impairment, learning and memory disorders, anxiety and depression [13], [14].

Vitamin D belongs to the group of fat-soluble vitamins. In addition to its regulatory functions in the skeletal system, vitamin D is now recognized as a hormone demonstration numerous extraskeletal effects [15]. In this context, vitamin D deficiency has so far been associated with many diseases ranging from cancer to psychiatric disorders [16]. It has also been suggested that vitamin D deficiency may cause negative effects in the brain [17]. Recently, it has been observed that this vitamin, directly affecting the nervous system, regulates brain functions and shows neuroprotective effects [18]. The brain is particularly susceptible to oxidative stress and damage due to its high oxygen consumption, lack of antioxidant enzymes, and high content of polyunsaturated fatty acid prone to oxidation [19]. Vitamin D, on the other hand, regulates the oxidant-antioxidant balance by increasing intracellular antioxidant concentration and reduces oxidative stress by removing excess free radicals [20]. Molecular oxidative damage in certain regions of the brain such as the hippocampus is associated with decreased cognition, learning and memory [21].

This study investigated behavioral changes associated with memory and learning caused by PFC damage induced by HFCS consumption. In the processes leading to the potential PFC damage in young rats fed with HFCS, the effects of an increased oxidative stress, disruption of cholinergic activity in PFC and neuronal growth were investigated. The aim of this study is to elucidate the neuroprotective and antioxidant effects of vitamin D on PFC damage, to reverse the cognitive impairment caused by HFCS in working memory and to explain the possible mechanisms of this process.

Section snippets
Animals, materials, and grouping
This study was initiated with the approval of the Animal Experiments Local Ethics Committee of Suleyman Demirel University (Number April 21, 2022/50). In this study, 24 male Wistar albino rats at the age of 6–8 weeks with a mean weight of 150 g were selected. The rats were obtained from the Experimental Animal Production and Experimental Research Laboratory of Suleyman Demirel University. During the experiment, all the rats (except for those receiving HFCS) were provided with ad libitum access. . . .

Weight change, fluid intake, blood glucose levels
The effect of HFCS on the rats’ weights was evaluated. No significant difference regarding body weight gain and terminal body weights was found between the groups (p > 0.05).

The fluid intake evaluation was based on water consumption in each cage with 8 rats in each. There was a significant increase in fluid intake in HFCS and HFCS + Vit D groups compared to the control group.

Blood glucose findings demonstrated that in week 2, there was a significant increase in HFCS group compared to the . . . . .

In this study, we investigated the possible damage to PFC by HFCS, which is frequently used as a dietary additive, and the therapeutic effects of vitamin D. For this purpose, monitoring of weight gain, fluid intake, blood glucose monitoring, behavioral tests, oxidative stress markers, and histopathological and immunohistochemical analyses were performed. It was shown that HFCS decreased cholinergic activity in PFC, leading to behavioral deterioration and memory decline, and vitamin D treatment. . . .

Study strengths and limitations
First of all, the choice of vitamin D as prophylactics for HFCS-induced damage, and the application of this method on the adolescent population as the target segment can be a strength of the study. Another strong side is that we primarily chose the PFC when evaluating the hippocampus in memory studies. Since the PFC is responsible for the integration of such functions as executive processes, memory, attention, perception of information, spontaneous speech, narrative expression, verbal fluency, . . . . .

In conclusion, our results showed that HFCS induced
oxidative stress,

  • neurobehavioral,
  • histological and immunological abnormalities, and
  • memory deficits in adolescent rats,

whereas treatment with vitamin D improved neurobehavioral and immunohistopathological markers, increased antioxidant activity, and enhanced memory. This effect may be attributed to the neuroprotective effect of vitamin D, its possible role in reducing neuronal oxidative stress, and enhancing cholinergic neurotransmission. . . . .

Some of the 51 References
  • M. Chini et al. Trends in prefrontal cortex development in health and disease: lessons from rodents and humans Trends Neurosci. (2021)
  • M.E. Patterson et al. Acute metabolic responses to high fructose corn syrup ingestion in adolescents with overweight/obesity and diabetes – J. Nutr. Intermed. Metab. (2018)
  • C.S. Harrell et al. – High-fructose diet during periadolescent development increases depressive-like behavior and remodels the hypothalamic transcriptome in male rats – Psychoneuroendocrinology (2015)
  • S.M. Coulibaly et al. – Effects of the methyl donors supplementation on hippocampal oxidative stress, depression and anxiety in chronically high fructose-treated rats – Neuroscience (2021)
  • S.N. Heiss et al. -When a spoonful of fallacies helps the sweetener go down: the corn refiner association’s use of straw-person arguments in health debates surrounding high-fructose corn syrup -Health Commun. (2016)
  • Health T.M. Hsu et al. – Effects of sucrose and high fructose corn syrup consumption on spatial memory function and hippocampal neuroinflammation in adolescent rats – Hippocampus (2015)

VitaminDWiki - High-fructose diet slows recovery from brain injury - TBI, rats - Oct 2015

VitaminDWiki - Fructose, HFCS and Vitamin D - many studies

which contains:
Scientists claim to have found root cause of obesity for most people (HFCS) - Oct 2023

7,700 studies resulted from a query for: ("high fructose" OR HFCS) "vitamin d" as of Dec 2023

Google Scholar

  • Cholecalciferol Prevent Obesity in Rats Under High Fat High Fructose Diet - Jan 2023 FREE PDF
  • Vitamin D3 supplementation improves glucose metabolism in the offspring of fructose-induced Sprague-Dawley rats 2022 DOI: 10.1530/endoabs.86.P207 presentation

HFCS is banned in much of Europe, including Sweden (Dec 2023) (not confirmed)


Brand-name foods that usually contain high fructose corn syrup

Heinz Tomato Ketchup
Skippy Reduced Fat Peanut Butter
Del Monte Canned Peaches
Oscar Mayer Smoked Lean White Turkey
Paula Dean salad dressings
Hawaiian Punch Fruit Juice (usually called “fruit drink” if it contains more HFSC than actual juice)
Del Monte Mexican Stewed Canned Tomatoes
Heinz Relish
Ritz Original Crackers
Honey Bunches of Oats breakfast cereal
Progresso Light canned Vegetable Barley Soup
Hunt's Pasta Sauce
Chef Boyardee Mac & Cheese
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A1 Steak Sauce
McDonald's Apple Pie
Yoplait Yogurt
Mountain Dew
Reese's Peanut Butter Cups
Mott's applesauce
Quaker Instant Oatmeal
Maruchan Ramen Noodles
Myoplex Deluxe Chocolate Peanut Butter Protein bar
Smuckers Fruit Preserves
Sweet Baby Ray's BBQ Sauce
Pearl Milling's (Aunt Jemima) pancake syrup
Moose Tracks Ice Cream
Quaker Chewy Granola Bars
Kroger Mild Viva Salsa.

Asked Google Bard about research of High Fructose Corn Syrup and Vitamin D - Dec 6, 2023

Research on High-Fructose Corn Syrup and Vitamin D
Several research studies have explored the potential interaction between high-fructose corn syrup (HFCS) and vitamin D. These studies suggest that HFCS may have a negative impact on vitamin D levels and function in the body.

Here are some key findings from the research:

  • HFCS may decrease vitamin D levels: Studies conducted on rodents and humans have shown that a diet high in HFCS can lead to lower levels of vitamin D in the blood. This is likely due to several factors, including:
    • Impaired absorption: Fructose in HFCS may interfere with the absorption of calcium and vitamin D from the intestines.
    • Increased excretion: High fructose intake may increase the amount of vitamin D that is excreted from the body in urine.
    • Deactivation: Some research suggests that HFCS may contribute to the deactivation of vitamin D in the body, reducing its biological activity.
    • HFCS may impair vitamin D function: Vitamin D plays a vital role in bone health, immune function, and other bodily processes. Studies suggest that HFCS may impair the ability of vitamin D to perform these functions.

For example, research in rats has shown that a diet high in HFCS can lead to:

  • Reduced bone density
  • Impaired immune function
  • Decreased cognitive function

Here are some specific studies that demonstrate the potential negative effects of HFCS on vitamin D:

  • Chronic High Fructose Intake Reduces Serum 1,25 (OH)2D3 Levels in Calcium-Sufficient Rodents: This study found that rats fed a diet high in HFCS had lower levels of vitamin D in their blood compared to rats fed a control diet.
  • Dietary Fructose Inhibits Intestinal Calcium Absorption and Induces Vitamin D Insufficiency in CKD: This study found that patients with chronic kidney disease who consumed a diet high in fructose had lower levels of vitamin D and calcium in their blood compared to those who consumed a control diet.
  • Protective Effect of Vitamin D on Learning and Memory Impairment in Rats Induced by High Fructose Corn Syrup: This study found that rats fed a diet high in HFCS had impaired learning and memory, which was partially reversed by treatment with vitamin D.

Overall, the research suggests that a diet high in HFCS may be detrimental to vitamin D status and function. While more research is needed to fully understand the nature of this interaction, it is important to be aware of the potential risks and consider limiting your intake of HFCS.

Here are some additional resources you may find helpful:

It is important to note that the research on HFCS and vitamin D is ongoing, and the long-term health implications of this interaction are still being investigated. However, the existing evidence suggests that it may be beneficial to limit your intake of HFCS to support optimal vitamin D status and health.