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Article ; Online: Effects of Polyphenols on Glucose-Induced Metabolic Changes in Healthy Human Subjects and on Glucose Transporters.

Williamson, Gary

2022 Volume 66, Issue 21, Page(s) e2101113

Abstract: Dietary polyphenols interact with glucose transporters in the small intestine and modulate glucose uptake after food or beverage consumption. This review assesses the transporter interaction in vitro and how this translates to an effect in healthy ... ...

Abstract	Dietary polyphenols interact with glucose transporters in the small intestine and modulate glucose uptake after food or beverage consumption. This review assesses the transporter interaction in vitro and how this translates to an effect in healthy volunteers consuming glucose. As examples, the apple polyphenol phlorizin inhibits sodium-glucose linked transporter-1; in the intestinal lumen, it is converted to phloretin, a strong inhibitor of glucose transporter-2 (GLUT2), by the brush border digestive enzyme lactase. Consequently, an apple extract rich in phlorizin attenuates blood glucose and insulin in healthy volunteers after a glucose challenge. On the other hand, the olive phenolic, oleuropein, inhibits GLUT2, but the strength of the inhibition is not enough to modulate blood glucose after a glucose challenge in healthy volunteers. Multiple metabolic effects and oxidative stresses after glucose consumption include insulin, incretin hormones, fatty acids, amino acids, and protein markers. However, apart from acute postprandial effects on glucose, insulin, and some incretin hormones, very little is known about the acute effects of polyphenols on these glucose-induced secondary effects. In summary, attenuation of the effect of a glucose challenge in vivo is only observed when polyphenols are strong inhibitors of glucose transporters.
MeSH term(s)	Humans ; Polyphenols/pharmacology ; Polyphenols/chemistry ; Glucose/metabolism ; Blood Glucose/metabolism ; Glucose Transport Proteins, Facilitative ; Incretins ; Phlorhizin/pharmacology ; Healthy Volunteers ; Insulin/metabolism ; Glucose Transporter Type 2
Chemical Substances	Polyphenols ; Glucose (IY9XDZ35W2) ; Blood Glucose ; Glucose Transport Proteins, Facilitative ; Incretins ; Phlorhizin (CU9S17279X) ; Insulin ; Glucose Transporter Type 2
Language	English
Publishing date	2022-04-06
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.202101113
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Article ; Online: A critical examination of human data for the biological activity of quercetin and its phase-2 conjugates.

Williamson, Gary / Clifford, Michael N

Critical reviews in food science and nutrition

2024 , Page(s) 1–37

Abstract: This critical review examines evidence for beneficial effects of quercetin phase-2 conjugates from clinical intervention studies, volunteer feeding trials, and in vitro work. Plasma concentrations of quercetin-3- ...

Abstract	This critical review examines evidence for beneficial effects of quercetin phase-2 conjugates from clinical intervention studies, volunteer feeding trials, and in vitro work. Plasma concentrations of quercetin-3-
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1037504-1
ISSN	1549-7852 ; 1040-8398
ISSN (online)	1549-7852
ISSN	1040-8398
DOI	10.1080/10408398.2023.2299329
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Article ; Online: Effects of Polyphenols on Glucose‐Induced Metabolic Changes in Healthy Human Subjects and on Glucose Transporters

Williamson, Gary

Molecular Nutrition & Food Research. 2022 Nov., v. 66, no. 21 p.e2101113-

2022

Abstract	Dietary polyphenols interact with glucose transporters in the small intestine and modulate glucose uptake after food or beverage consumption. This review assesses the transporter interaction in vitro and how this translates to an effect in healthy volunteers consuming glucose. As examples, the apple polyphenol phlorizin inhibits sodium‐glucose linked transporter‐1; in the intestinal lumen, it is converted to phloretin, a strong inhibitor of glucose transporter‐2 (GLUT2), by the brush border digestive enzyme lactase. Consequently, an apple extract rich in phlorizin attenuates blood glucose and insulin in healthy volunteers after a glucose challenge. On the other hand, the olive phenolic, oleuropein, inhibits GLUT2, but the strength of the inhibition is not enough to modulate blood glucose after a glucose challenge in healthy volunteers. Multiple metabolic effects and oxidative stresses after glucose consumption include insulin, incretin hormones, fatty acids, amino acids, and protein markers. However, apart from acute postprandial effects on glucose, insulin, and some incretin hormones, very little is known about the acute effects of polyphenols on these glucose‐induced secondary effects. In summary, attenuation of the effect of a glucose challenge in vivo is only observed when polyphenols are strong inhibitors of glucose transporters.
Keywords	apples ; beta-galactosidase ; beverages ; blood glucose ; digestive enzymes ; food research ; glucose ; humans ; insulin ; microvilli ; nutrition ; oleuropein ; olives ; polyphenols ; secretin ; small intestine
Language	English
Dates of publication	2022-11
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	REVIEW
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.202101113
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Article ; Online: Protection against developing type 2 diabetes by coffee consumption: assessment of the role of chlorogenic acid and metabolites on glycaemic responses.

Williamson, Gary

Food & function

2020 Volume 11, Issue 6, Page(s) 4826–4833

Abstract: Epidemiological studies show a convincing long-term and dose-dependent protection of coffee and decaffeinated coffee against developing type 2 diabetes. The mechanisms of this effect are still not understood even though several have been proposed, ... ...

Abstract	Epidemiological studies show a convincing long-term and dose-dependent protection of coffee and decaffeinated coffee against developing type 2 diabetes. The mechanisms of this effect are still not understood even though several have been proposed, including a potential effect on blood glucose by chlorogenic acids. However, there is minimal effect of decaffeinated coffee on postprandial blood glucose and insulin when consumed with carbohydrates, although there may be effects on incretin hormones, but these have been measured in only a few studies. Although chlorogenic acids do not affect carbohydrate digestion directly, they may affect glucose absorption and subsequent utilisation, the latter through metabolites derived from endogenous pathways or action of the gut microbiota. To advance understanding of the protective effect of coffee chlorogenic acids, more chronic intervention studies are needed on decaffeinated coffee, coupled with mechanistic studies in vitro using more realistic concentrations of the relevant chlorogenic acid metabolites.
MeSH term(s)	Blood Glucose/drug effects ; Chlorogenic Acid/metabolism ; Chlorogenic Acid/pharmacology ; Coffee ; Diabetes Mellitus, Type 2/prevention & control ; Humans ; Postprandial Period
Chemical Substances	Blood Glucose ; Coffee ; Chlorogenic Acid (318ADP12RI)
Language	English
Publishing date	2020-06-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/d0fo01168a
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Article ; Online: Reporting of plasma antioxidant activities in human intervention studies in the

Williamson, Gary

The British journal of nutrition

2019 Volume 122, Issue 7, Page(s) 721–722

MeSH term(s)	Antioxidants/metabolism ; Biomarkers/blood ; Humans ; Nutritional Status ; Research Design
Chemical Substances	Antioxidants ; Biomarkers
Language	English
Publishing date	2019-07-16
Publishing country	England
Document type	Editorial
ZDB-ID	280396-3
ISSN	1475-2662 ; 0007-1145
ISSN (online)	1475-2662
ISSN	0007-1145
DOI	10.1017/S0007114519001697
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Article ; Online: Systematic Review and Quantitative Data Synthesis of Peripheral Blood Mononuclear Cell Transcriptomics Reveals Consensus Gene Expression Changes in Response to a High Fat Meal.

Dordevic, Aimee L / Williamson, Gary

Molecular nutrition & food research

2023 Volume 67, Issue 23, Page(s) e2300512

Abstract: Scope: Metabolic flexibility is essential for a healthy response to a high fat meal, and is assessed by measuring postprandial changes in blood markers including peripheral blood mononuclear cells (PBMCs; lymphocytes and monocytes). However, there is no ...

Abstract	Scope: Metabolic flexibility is essential for a healthy response to a high fat meal, and is assessed by measuring postprandial changes in blood markers including peripheral blood mononuclear cells (PBMCs; lymphocytes and monocytes). However, there is no clear consensus on postprandial gene expression and protein changes in these cells. Method and results: The study systematically reviews the literature reporting transcriptional and proteomic changes in PBMCs after consumption of a high fat meal. After re-analysis of the raw data to ensure equivalence between studies, ≈85 genes are significantly changed (defined as in the same direction in ≥3 studies) with about half involved in four processes: inflammation/oxidative stress, GTP metabolism, apoptosis, and lipid localization/transport. For meals consisting predominantly of unsaturated fatty acids (UFA), notable additional processes are phosphorylation and glucocorticoid response. For saturated fatty acids (SFA), genes related to migration/angiogenesis and platelet aggregation are also changed. Conclusion: Despite differences in study design, common gene changes are identified in PBMCs following a high fat meal. These common genes and processes will facilitate definition of the postprandial transcriptome as part of the overall postcibalome, linking all molecules and processes that change in the blood after a meal.
MeSH term(s)	Dietary Fats/pharmacology ; Transcriptome ; Leukocytes, Mononuclear/metabolism ; Consensus ; Proteomics ; Meals ; Postprandial Period ; Cross-Over Studies ; Triglycerides
Chemical Substances	Dietary Fats ; Triglycerides
Language	English
Publishing date	2023-10-10
Publishing country	Germany
Document type	Systematic Review ; Journal Article
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.202300512
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Article ; Online: Review of factors affecting citrus polyphenol bioavailability and their importance in designing in vitro, animal, and intervention studies.

Visvanathan, Rizliya / Williamson, Gary

Comprehensive reviews in food science and food safety

2022 Volume 21, Issue 6, Page(s) 4509–4545

Abstract: Evidence from in vitro, animal, and human studies links citrus fruit consumption with several health-promoting effects. However, many in vitro studies disregard bioavailability data, a key factor determining responses in humans. Citrus (poly)phenol ... ...

Abstract	Evidence from in vitro, animal, and human studies links citrus fruit consumption with several health-promoting effects. However, many in vitro studies disregard bioavailability data, a key factor determining responses in humans. Citrus (poly)phenol metabolism and bioavailability follow specific pathways that vary widely among individuals and are affected by several intrinsic (age, sex, gut microbiota, metabolic state, genetic polymorphisms) and extrinsic (food matrix, co-consumed food, (poly)phenol solubility, dose, food processing, lifestyle) factors. The gut microbiota is crucial to both absorption of citrus (poly)phenols and the production of catabolites, and absorption of both takes place mostly in the colon. Citrus (poly)phenol absorption can reach up to 100% in some individuals when the sum of the gut microbiota products are taken into account. This review emphasizes the importance of understanding citrus (poly)phenol absorption, metabolism, and bioavailability using evidence primarily derived from human studies in designing in vitro, animal, and further human clinical studies.
MeSH term(s)	Animals ; Humans ; Polyphenols ; Citrus ; Biological Availability ; Phenol ; Phenols
Chemical Substances	Polyphenols ; Phenol (339NCG44TV) ; Phenols
Language	English
Publishing date	2022-10-01
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2185829-9
ISSN	1541-4337 ; 1541-4337
ISSN (online)	1541-4337
ISSN	1541-4337
DOI	10.1111/1541-4337.13057
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Article ; Online: Effects of (poly)phenols on circadian clock gene-mediated metabolic homeostasis in cultured mammalian cells: a scoping review.

Sulaimani, Noha / Houghton, Michael J / Bonham, Maxine P / Williamson, Gary

Advances in nutrition (Bethesda, Md.)

2024 , Page(s) 100232

Abstract: Metabolic homeostasis is regulated by circadian clocks. Disruption to our circadian clocks, by lifestyle behaviors such as timing of eating and sleeping, has been linked to increased rates of metabolic disorders. There is now considerable evidence that ... ...

Abstract	Metabolic homeostasis is regulated by circadian clocks. Disruption to our circadian clocks, by lifestyle behaviors such as timing of eating and sleeping, has been linked to increased rates of metabolic disorders. There is now considerable evidence that selected dietary (poly)phenols, including flavonoids, phenolic acids and tannins, may modulate both metabolic and circadian processes. This review evaluates the effects of (poly)phenols on circadian clock genes and linked metabolic homeostasis in vitro, and potential mechanisms of action, by critically evaluating the literature on mammalian cells. A systematic search was conducted to ensure full coverage of the literature, and identified 43 relevant studies addressing the effects of (poly)phenols on cellular circadian processes. Nobiletin and tangeretin, found in citrus, (-)-epigallocatechin-3-gallate from green tea, urolithin A, a gut microbial metabolite from ellagitannins in fruit, curcumin, bavachalcone, cinnamic acid and resveratrol at low micromolar concentrations all affect circadian molecular processes in multiple types of synchronized cells. Nobiletin emerges as a putative Retinoic acid-related Orphan Receptor (RORα/γ) agonist, leading to induction of the circadian regulator Brain and Muscle ARNT-Like 1 (BMAL1), and increased Period Circadian Regulator 2 (PER2) amplitude and period. These effects are clear despite substantial variations in the protocols employed, and this review suggests a methodological framework to help future study design in this emerging area of research.
Language	English
Publishing date	2024-04-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2583634-1
ISSN	2156-5376 ; 2156-5376
ISSN (online)	2156-5376
ISSN	2156-5376
DOI	10.1016/j.advnut.2024.100232
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Article: Protection against developing type 2 diabetes by coffee consumption: assessment of the role of chlorogenic acid and metabolites on glycaemic responses

Williamson, Gary

Food & function. 2020 June 24, v. 11, no. 6

2020

Abstract	Epidemiological studies show a convincing long-term and dose-dependent protection of coffee and decaffeinated coffee against developing type 2 diabetes. The mechanisms of this effect are still not understood even though several have been proposed, including a potential effect on blood glucose by chlorogenic acids. However, there is minimal effect of decaffeinated coffee on postprandial blood glucose and insulin when consumed with carbohydrates, although there may be effects on incretin hormones, but these have been measured in only a few studies. Although chlorogenic acids do not affect carbohydrate digestion directly, they may affect glucose absorption and subsequent utilisation, the latter through metabolites derived from endogenous pathways or action of the gut microbiota. To advance understanding of the protective effect of coffee chlorogenic acids, more chronic intervention studies are needed on decaffeinated coffee, coupled with mechanistic studies in vitro using more realistic concentrations of the relevant chlorogenic acid metabolites.
Keywords	absorption ; blood glucose ; chlorogenic acid ; decaffeination ; digestion ; dose response ; epidemiological studies ; glucose ; glycemic effect ; insulin ; intestinal microorganisms ; metabolites ; noninsulin-dependent diabetes mellitus ; protective effect ; secretin
Language	English
Dates of publication	2020-0624
Size	p. 4826-4833.
Publishing place	The Royal Society of Chemistry
Document type	Article
Note	NAL-light
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/d0fo01168a
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Exploring the anti-inflammatory activity of sulforaphane.

Treasure, Katie / Harris, James / Williamson, Gary

Immunology and cell biology

2023 Volume 101, Issue 9, Page(s) 805–828

Abstract: Dysregulation of innate immune responses can result in chronic inflammatory conditions. Glucocorticoids, the current frontline therapy, are effective immunosuppressive drugs but come with a trade-off of cumulative and serious side effects. Therefore, ... ...

Abstract	Dysregulation of innate immune responses can result in chronic inflammatory conditions. Glucocorticoids, the current frontline therapy, are effective immunosuppressive drugs but come with a trade-off of cumulative and serious side effects. Therefore, alternative drug options with improved safety profiles are urgently needed. Sulforaphane, a phytochemical derived from plants of the brassica family, is a potent inducer of phase II detoxification enzymes via nuclear factor-erythroid factor 2-related factor 2 (NRF2) signaling. Moreover, a growing body of evidence suggests additional diverse anti-inflammatory properties of sulforaphane through interactions with mediators of key signaling pathways and inflammatory cytokines. Multiple studies support a role for sulforaphane as a negative regulator of nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) activation and subsequent cytokine release, inflammasome activation and direct regulation of the activity of macrophage migration inhibitory factor. Significantly, studies have also highlighted potential steroid-sparing activity for sulforaphane, suggesting that it may have potential as an adjunctive therapy for some inflammatory conditions. This review discusses published research on sulforaphane, including proposed mechanisms of action, and poses questions for future studies that might help progress our understanding of the potential clinical applications of this intriguing molecule.
MeSH term(s)	Isothiocyanates/pharmacology ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Sulfoxides ; Signal Transduction
Chemical Substances	sulforaphane (GA49J4310U) ; Isothiocyanates ; Anti-Inflammatory Agents ; Sulfoxides
Language	English
Publishing date	2023-08-31
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12686
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