High fructose consumption: more pain than gain to human health

8 An imbalance in any metabolic system can be traced to its homeostasis. When homeostatic environment is not 9 attainable then there will be a response from the body. A new shift has emerged, “the negative feedback effect of 10 high fructose consumption;” more pain than gain. The human metabolic system daily combat fructose sugar 11 metabolism which emanates from high consumption. This inadvently lead to a chronological series of 12 complications arising from the feedback. These feedbacks play pivotal roles in skeletal muscle damage and other 13 body frameworks, it also fosters toxic advanced glycation end products (AGEs), factors that impose and inflict 14 damaging effects to the body`s energy currency and serious threat to health. These damages are missed or 15 overlooked because of early nonspecific physiological symptoms. High level of fructose has both long- and short- 16 term effects on human metabolic processes. These effects which are majorly through the production of reactive 17 oxygen species (ROS) and other free radicals, are felt in the disruption of biomolecules such as causing DNA 18 mutation, lipid peroxidation etc. these effects in turn lead to various diseases such as cancer, diabetes, 19 atherosclerosis, and other health issues. In this review, we will focus on the damaging effects this sugar has on 20 human health and the present solutions being applied. We will also look at the next step in combatting and 21 controlling these negative feedbacks.


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The exasperate negative feedback mechanism has been linked to an increased risk of a broad range of chronic 25 metabolic diseases. Namely, cardiovascular disease, diabetes, dyslipidaemia, obesity, hyperglycaemia, high 26 triglyceride centred on the concept "you are what you eat." How about the industrialized sweeten dairy 27 contribution to this feedback loop with its negative outcomes in society, thus producing a considerable economic 28 and medical burden on our healthcare system, existing literature highlights that dysfunctional insulin, liver due to 29 excessive fructose ingestion has detrimental outcome linked to depleted ATP, metabolic syndrome, non-alcoholic 30 fatty liver disease etc. All this research centred on the immediate manifestation 31 What of its long-term effects on metabolic system that is synonymous with a slow, gradual progression into 32 oxidative stress, free radicals' generation that exact consequence on basic molecules such as DNA, lipids, and 33 proteins which are the building blocks that aid longevity of life span; aids chronic inflammation and causes 34 oxidative modifications of enzymes, lipid peroxidation. Thus, deterioration of the antioxidant defense mechanism 35 altars redox regulation. These are critical for cell viability. Elucidating the effects in the future and continues to 36 be an important handicap in resource-poor countries. In this review, we discussed the future outcome, potentiating 37 high fructose ingestion on metabolic system of the body 38 High fructose diet is deleterious to the human metabolic system. This is a major concern as most of the metabolic 39 health problems have been associated with high fructose consumption. Diseases such as cardiovascular disease, 40 diabetes, dyslipidaemia, obesity, hyperglycaemia, and high triglyceride [1,2] have all been mentioned. Its high 41 consumption has risen since it is used as sweetener in most packaged diets. High fructose diet intake has been effect of prolonged consumption of high fructose sugar and the need for supplementation to boost the system 66 defence mechanism and cell longevity.

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In 1960, high-fructose corn syrup (HFCS) was developed as a result of scientist invention of technologies that 80 allow corn starch to be remolded into HFCS [15,16]. This HFCS contains high fructose level, it is inexpensive 81 and in acidic condition; it is stable in foods as well as in beverages. However, its consumption has increased and 82 doubled between 1970 and 1990. HFCS contains 55% of free fructose with 42% of free glucose, while 3% portion 83 of HFCS is for other sugars, this has significantly increased fructose consumption making a total tall of 85 to 100g 84 per day [17]. Nowadays, HFCS is used in the manufacturing of processed foods as well as beverages in place of 85 sucrose; these processed products include sodas, candies, drinks, juices, cereals, dairy products, and jams, among 86 others. The increased usage of HFCS arises from its low cost, its high concentration of sweetness as well as its 87 ability to improve the shelf life of products [17].

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It has been postulated that high level of HFCS food can bring about increase in lipogenesis, high levels of plasma 89 triacyclglycerols (TAGs), obesity and cardiovascular abnormalities [18]. When ingested in large amounts, 90 fructose can cause hepatic insulin resistance, leptin resistance, accumulation of ectopic fat in the liver and skeletal 91 muscle, with visceral fat mass accumulation as well as increase in total fat [19]. It is known that moderate amount 92 of fructose does not have any negative effect, mainly because there is decrease in the response to glucose loads, 3 of fructose into fructose 1-phosphate as seen in the above (Figure 2). The fructose 1-phosphate is then taken up 99 and metabolised in the liver where it is directed towards replenishment of liver glycogen and triglyceride synthesis.

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Thus, when the liver takes up ingested fructose, it may produce CO2 after being oxidized and this can further lead 101 to the production of glucose and lactate in the biological system when it is further converted. Both lactate and 102 glucose produced are then either allowed or enable to escape into circulation for extrahepatic metabolism, or it is 103 converted to fat and hepatic glycogen. The phosphorylation and enormous absorption of fructose within liver 104 causes massive ATP to AMP as well as uric acid degradation [21][22][23][24]. Steady fructose ingestion prompts de novo 105 lipogenesis, causes high level accumulation of hepatic fatty acids in the body, and can result to ectopic liver fat 106 when stored or deposited due to lack of usage by the body system or it is secreted as VLDL-triacylglycerols. Also,  [27]. It is also known as syndrome X, 119 insulin resistance syndrome, or multiple risk factor syndrome [28]. The classified risk conditions range from 120 diabetes, hyperglycaemia, dyslipidaemia, cardiovascular diseases and obesity [29]. Diabetes is a disease condition 121 characterised by a severe hyperglycaemia (increase in blood glucose level in the body system) due to either defects

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Metabolic syndrome also causes cardiovascular diseases which generally refer to conditions that lead to either 127 partial or total blockage of the blood vessels resulting to heart failure, stroke, chest pain and heart attack [32].

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Skeletal muscle is different from other muscles in the sense that it is the single one of its kind that can sporadically Commonly produced as biochemical reactions intermediate that is impermeable to cell membranes and its negatively charged with hydroxyperoxyl radical being an exception. It has long half-life and can be produced by many cells when fighting against pathogens. Dismutation of hydrogen peroxide in the cells by superoxide dismutase helps to prevent damages within the biological system. [52,53] Hydroxyl radicals They are very reactive due to their strong oxidizing potential. They would normally cause damage to surrounding molecules. They are the most damaging ROS and can be said to be non-existing if not for the presence of some products of their reactions. They are not permeable. [54,55] Singlet oxygen Another essential ROS with limited half-life yet; permeable to cell membranes. It is oxygen in its excited state but without unpaired electrons so it cannot be termed as a radical. In water, the dismutation of superoxide anion brings about the production of high oxidizing singlet oxygen.

Hyperchlorite
It is formed because of the activity of myeloperoxidase in the biological system using hydrogen peroxide. It is frequently created via the action of neutrophils also hazardous to thiols, ascorbate, lipids, and NADPH. In acidic form, it is permeable to cell membranes.
[58, 59] Peroxynitrite This is produced from the reaction between nitric oxide and superoxide. It is a fast reaction even more rapid in reaction than NO with a protein's heme. It is a strong oxidizing agent that can damage DNA, reduce thiol groups and subsequently cause protein damage.

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These active metabolites that reduces the concentration of ROS which is toxic to the body are gotten from a variety 312 of food and beverages such as coffee, tea, vegetables, fruits, cocoa shells, olives, garlic, ginger, red onion skin,

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They all contribute to protecting the cells against free radical damage. Vitamin E, also known as tocopherol, is

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Another important non-enzymatic antioxidant is α-lipoic acid, a natural compound present in a variety of foods

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[132]. It serves as cofactor for α-dehydrogenase complexes and participates in some cellular reactions as well. It 378 has been concluded by many studies that α-lipoic acid can recycle vitamin C [133]. Light exercise may increase 379 its level in skeletal muscle fibers, but prolonged and constant exercise does not [133]. Other known non-enzymatic