Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention

Saris, Christiaan G J; Timmers, Silvie

doi:10.3389/fnut.2022.947567

Cited by 12 publications

(7 citation statements)

References 179 publications

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“…Increased ketone bodies in resistant cancer cells disrupt their survival and proliferation, inhibit glycolysis, and block the main pathway of energy production (22,24). Ketone supplementation or a ketogenic diet has shown positive therapeutic advantages in various malignancies, potentially targeting tumour metabolism as a new area for drug discovery (25). The molecular pathways affected by ketone body treatment in cancer cells include the JAK-STAT and mTOR pathways, which lead to decreased cell migration and inhibition of cellular growth and proliferation.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the clinical utility of apitolisib/ vorinostat combination in apitolisib-resistant H1975 lung adenocarcinoma

Hmmier,

Dowling

2024

Preprint

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Background: The PI3K signalling pathway regulates the metabolic activity of cells. Disruption by PI3K inhibitors causes an aerobic/anaerobic imbalance that decreases energy production and cell growth. Cancer cells adapt to PI3K inhibitors in order to reduce their effectiveness. Resistance to apitolisib could be due to intrinsic factors or acquired adaptation. Oncologists often ask whether to discontinue apitolisib, increase its dose, or use a drug combination. Methods: We observed the proliferation of resistant cells in (H1975R+) and out (H1975R-) of apitolisib treatment, cell cycle pattern, energy phenotyping/reprogramming, and the effects of combining Apitolisib with Vorinostat on the acquired proliferation of H1975R- cells. Results: The Proliferation of H1975R- cells increased, while that of H1975R+ cells remained suppressed. Both conditions showed a 5x decrease in the number of cells at the Go/G1 phase and doubled at S and G2/M phases (p< 0.0001). H1975R- cell survival was 80% compared with 20% in H975R+ cells treated with 7 μM vorinostat. Vorinostat effectively controlled acquired hyperproliferation of H1975R- cells. Conclusion: If a tumour becomes unresponsive to apitolisib, it is advisable to continue the inhibitor and consider a combination with non-tyrosine kinase inhibitors.

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Section: Discussionmentioning

confidence: 99%

Evaluating the clinical utility of apitolisib/ vorinostat combination in apitolisib-resistant H1975 lung adenocarcinoma

Hmmier,

Dowling

2024

Preprint

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“…Nutritional ketosis can be induced by various dietary modifications, including KD, ketone supplementation, intermittent fasting, or calorie restriction [ 6 ], and is considered effective for weight loss, improved cognitive function, and cancer protection [ 6 ]. It has an inverse association between the blood ketone concentration and insulin resistance in subjects with T2DM [ 13 ], suggesting a relationship between nutritional ketosis and insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Ketogenic diet preserves muscle mass and strength in a mouse model of type 2 diabetes

Park,

Yang

2024

PLoS ONE

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Diabetes is often associated with reduced muscle mass and function. The ketogenic diet (KD) may improve muscle mass and function via the induction of nutritional ketosis. To test whether the KD is able to preserve muscle mass and strength in a mouse model of type 2 diabetes (T2DM), C57BL/6J mice were assigned to lean control, diabetes control, and KD groups. The mice were fed a standard diet (10% kcal from fat) or a high-fat diet (HFD) (60% kcal from fat). The diabetic condition was induced by a single injection of streptozotocin (STZ; 100 mg/kg) and nicotinamide (NAM; 120 mg/kg) into HFD-fed mice. After 8-week HFD feeding, the KD (90% kcal from fat) was fed to the KD group for the following 6 weeks. After the 14-week experimental period, an oral glucose tolerance test and grip strength test were conducted. Type 2 diabetic condition induced by HFD feeding and STZ/NAM injection resulted in reduced muscle mass and grip strength, and smaller muscle fiber areas. The KD nutritional intervention improved these effects. Additionally, the KD altered the gene expression of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome- and endoplasmic reticulum (ER) stress-related markers in the muscles of diabetic mice. Collectively, KD improved muscle mass and function with alterations in NLRP3 inflammasome and ER stress.

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“…The increase in blood or urine levels of ketone bodies, namely ketosis, is a metabolic condition that takes place in course of low glucose availability, generally deriving from low-carbohydrate diets or a fasting state [ 23 ]. Ketosis, by itself, is a condition of metabolic stress which may exacerbate the clinical risk of pre-existing disease conditions such as liver, kidney, or pancreatic insufficiency [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Ketone Body β-Hydroxy-Butyrate Sustains Progressive Motility in Capacitated Human Spermatozoa: A Possible Role in Natural Fertility

et al. 2023

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Background Calorie restriction is recognized as a useful nutritional approach to improve the endocrine derangements and low fertility profile associated with increased body weight. This is particularly the case for dietary regimens involving ketosis, resulting in increased serum levels of ketone bodies such as β-hydroxy-butyrate (β-HB). In addition to serum, β-HB is detected in several biofluids and β-HB levels in the follicular fluid are strictly correlated with the reproductive outcome in infertile females. However, a possible direct role of ketone bodies on sperm function has not been addressed so far. Methods Semen samples were obtained from 10 normozoospermic healthy donors attending the University Andrology Unit as participants in an infertility survey programme. The effect of β-HB on cell motility in vitro was evaluated on isolated spermatozoa according to their migratory activity in a swim-up selection procedure. The effect of β-HB on spermatozoa undergone to capacitation was also assessed. Results Two hours of exposure to β-HB, 1 mM or 4 mM, proved to be ineffective in modifying the motility of freshly ejaculated spermatozoa isolated according to the migratory activity in a swim-up procedure (all p values > 0.05). Differently, sperm maintenance in 4 mM β-HB after capacitation was associated with a significantly higher percentage of sperm cells with progressive motility compared to β-HB-lacking control (respectively, 67.6 ± 3.5% vs. 55.3 ± 6.5%, p = 0.0158). Succinyl-CoA transferase inhibitor abolished the effect on motility exerted by β-HB, underpinning a major role for this enzyme. Conclusion Our results suggest a possible physiological role for β-HB that could represent an energy metabolite in support of cell motility on capacitated spermatozoa right before encountering the oocyte.

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Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention

Cited by 12 publications

References 179 publications

Evaluating the clinical utility of apitolisib/ vorinostat combination in apitolisib-resistant H1975 lung adenocarcinoma

Evaluating the clinical utility of apitolisib/ vorinostat combination in apitolisib-resistant H1975 lung adenocarcinoma

Ketogenic diet preserves muscle mass and strength in a mouse model of type 2 diabetes

Ketone Body β-Hydroxy-Butyrate Sustains Progressive Motility in Capacitated Human Spermatozoa: A Possible Role in Natural Fertility

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