Fructose spike control: potential health benefits and plant naturals
Publication Date
July 16, 2024
Creator
Heath, Alan David
Abstract
Fructose has been linked to, and even claimed, although controversially, to be the cause of the obesity, diabetes and metabolic syndrome global epidemics. However, many early studies have been conducted in animals and humans at very high doses. Following an in-depth literature review, with consideration of fructose intake levels consumed in a normal diet, it is concluded here that there is reasonable evidence that fructose can in particular increase post-prandial triglycerides.
This fits well with dietary fructose, unlike glucose, being relatively unregulated by insulin and is instead mostly and rapidly metabolised in the liver. That metabolism of fructose is not feedback inhibited by energy status has led to suggestions that it is more readily utilised for lipid synthesis. It has also been proposed that only fructose in excess of energy requirements is directed towards or stimulates de novo lipogenesis. This thesis therefore hypothesised that flattening the fructose spike reaching the liver from the small intestine would result in reduced triglyceride release from the liver.
Triglyceride release was investigated in primary human hepatocytes treated with high physiological levels of fructose verses and half such levels for twice as long, hence modelling “flattening the fructose spike” at 6, 8 10, 12 and 14 mM glucose, over three applications to represent “meals” during the course of the day. Triglyceride (meal 1- mean of 8 mM fructose for 1 hrs vs. 4 mM fructose for 2 hrs- 47%; meal 2- mean of 2 mM fructose for 1 hr vs. 1 mM fructose for 2 hrs- 65%; meal 2- mean of 8 mM fructose for 1 hr vs. 4 mM fructose 2hrs- 73%; meal 3- 2 mM fructose for 1 hr vs. 1 mM fructose for 2 hrs- 58%; meal 3- 8 mM fructose for 1 hr vs. 4 mM fructose for 2 hr- 39%) and cytotoxicity (meal 1- 8 mM fructose for 1 hr vs. 4 mM fructose for 2 hrs- 17%; meal 2- 8 mM fructose for 1 hr vs 4 mM for 2 hrs- 43%; meal 3- 8 mM fructose for 1 hrs vs. 4 mM fructose for 2 hrs- 28%) were found to be significantly decreased.
As natural plant extracts to potentially flatten the fructose spike and limit triglyceride release, black and green tea were found, in an optimised gut cell-line, to significantly inhibit fructose and glucose transport (60% and 82% respectively at a 1-in-4 dilution). Synergies with glucose inhibitors (phloretin+quercetin-3-glucoside; luteolin+quercetin-3-glucoside; hesperitin+quercetin-3-glucoside, luteolin+lectin, black tea+phloridzin, green tea+phloridzin and ice tea+phloridzin) were found to be significant for glucose transport inhibition. By slowing down fructose and glucose uptake in the gut such compounds and plant extracts could also activate the ileal brake and reduce appetite and energy intake.
Investigation into further potential health benefits of flattening the fructose spike found that over 72 hrs fructose+glucose induced excess glycogen storage (2.5-fold), over 24 hrs elevated lactate (3-fold) and over 48 hrs intact/total FGF21 (2.2-fold) and greatly more so than isocaloric glucose alone (1.76, 2.88 and 2.1-fold respectively). Over 24 hrs glucose tended to increase intake/FGF21 more so than fructose, which correlated negatively with fibroblast activation protein. Significant lipid accumulation was not seen in these experiments with fructose or glucose.
In conclusion this thesis has: determined that inhibiting fructose transport in the gut has the potential to reduce triglyceride release; identified natural plant compounds and extracts to do so; and found excess glycogen, lactate and FGF21 as further potential health markers that may be further investigated in primary human hepatocytes, the gold standard of in vitro liver models avoiding the use of animals and expense of human subjects.
Item Type
ethesis
Thesis Type
PhD
Supervisors
Subjects (LC)
Associated Schools / Departments
School of Life Sciences
eprints ID
76752
UoN Repository URI
Except where otherwise noted, this item's license is described as
File(s)![Thumbnail Image]()
Name
Corrections highlighted for examiner- Alan Heath PhD- Thesis Fructose Spike Control.pdf
Type
Full-text
Description
Examined. Corrections highlighted for examiner
Size
3.48 MB
Format
Adobe PDF
Checksum (MD5)
2c9a92a7c08b27e9271352b075eb8daf