Anti-aging effect of DL-β-hydroxybutyrate against hepatic cellular senescence induced by D-galactose or γ-irradiation via autophagic flux stimulation in male rats - ScienceDirect

https://www.sciencedirect.com/science/article/pii/S0167494320302855

 

"Taken together, these findings suggest that βOHB may be useful in combating hepatic cellular senescence induced by d-galactose or γ-irradiation via autophagy dependent mechanisms."

 Habieb, M. E., Mohamed, M. A., El Gamal, D. M., Hawas, A. M. & Mohamed, T. M. (2021). Anti-aging effect of DL-β-hydroxybutyrate against hepatic cellular senescence induced by D-galactose or γ-irradiation via autophagic flux stimulation in male rats. Archives of Gerontology and Geriatrics, 92, s. 104288. doi:https://doi.org/10.1016/j.archger.2020.104288

The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease - PubMed

https://pubmed.ncbi.nlm.nih.gov/25686106/

"Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome"

Youm YH, Nguyen KY, Grant RW, et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med. 2015;21(3):263-269. doi:10.1038/nm.3804

Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? - PubMed

https://pubmed.ncbi.nlm.nih.gov/21885251/

 

Abstract

Malignant brain cancer persists as a major disease of morbidity and mortality. The failure to recognize brain cancer as a disease of energy metabolism has contributed in large part to the failure in management. As long as brain tumor cells have access to glucose and glutamine, the disease will progress. The current standard of care provides brain tumors with access to glucose and glutamine. The high fat low carbohydrate ketogenic diet (KD) will target glucose availability and possibly that of glutamine when administered in carefully restricted amounts to reduce total caloric intake and circulating levels of glucose. The restricted KD (RKD) targets major signaling pathways associated with glucose and glutamine metabolism including the IGF-1/PI3K/Akt/Hif pathway. The RKD is anti-angiogenic, anti-invasive, anti-inflammatory, and pro-apoptotic when evaluated in mice with malignant brain cancer. The therapeutic efficacy of the restricted KD can be enhanced when combined with drugs that also target glucose and glutamine. Therapeutic efficacy of the RKD was also seen against malignant gliomas in human case reports. Hence, the RKD can be an effective non-toxic therapeutic option to the current standard of care for inhibiting the growth and invasive properties of malignant brain cancer.

 

Seyfried TN, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Res. 2012 Jul;100(3):310-26. doi: 10.1016/j.eplepsyres.2011.06.017. Epub 2011 Aug 31. PMID: 21885251.

 

In Alzheimer Research, Glucose Metabolism Moves to Center Stage

https://jamanetwork.com/journals/jama/fullarticle/2758712

”Six weeks after completing the modified ketogenic diet, patients had improved Alzheimer disease biomarkers in their cerebrospinal fluid. “With the ketogenic diet, we are moving the β-amyloid in a healthier direction,” Craft said. Patients also had better blood flow to the hippocampus and improved body-wide insulin sensitivity. A larger trial of the modified ketogenic diet is now under way.”

Kuehn BM. In Alzheimer Research, Glucose Metabolism Moves to Center Stage. JAMA.2020;323(4):297–299. doi:10.1001/jama.2019.20939

Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model | bioRxiv

https://www.biorxiv.org/content/10.1101/2020.09.11.294363v1





These data underscore the value of mCoV-A59 model to test mechanism and
establishes harnessing of the ketogenic immunometabolic checkpoint as a
potential treatment against COVID-19 in the elderly.



 Ryu, S. et al. (2020). Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model. bioRxiv, s. 2020.09.11.294363. doi:10.1101/2020.09.11.294363

Cuprizone-Induced Demyelination in Mouse Hippocampus Is Alleviated by Ketogenic Diet | Journal of Agricultural and Food Chemistry

https://pubs.acs.org/doi/abs/10.1021/acs.jafc.0c04604?fbclid=IwAR3NQr1SoE8l4biBINF2exSmPzSDthUykseDvf7FR1VaiZiP3Ub9MHIgong&





In conclusion, ketogenic diet exerted a neuroprotective effect on cuprizone-induced
demyelination mice, and this activity was associated with the modulation
of the SIRT1/PPAR-γ and SIRT1/P-Akt/mTOR pathways.



J. Agric. Food Chem. 2020, XXXX, XXX, XXX-XXX

Publication Date:September 12, 2020

https://doi.org/10.1021/acs.jafc.0c04604

Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial | The BMJ

https://www.bmj.com/content/363/bmj.k4583



Conclusions Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.

Ebbeling Cara B, Feldman Henry A, Klein Gloria L, Wong Julia M W, Bielak Lisa, Steltz Sarah K et al.Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial BMJ 2018; 363 :k4583

To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease | Advances in Nutrition | Oxford Academic

https://academic.oup.com/advances/article-abstract/doi/10.1093/advances/nmaa073/5864685



""... interventions, and outcome measures, ketogenic therapy appears promising
in improving both acute and long-term cognition among patients with
Alzheimer disease/mild cognitive impairment."


Maria G Grammatikopoulou, Dimitrios G Goulis, Konstantinos Gkiouras,
Xenophon Theodoridis, Kalliopi K Gkouskou, Athanasios Evangeliou,
Efthimis Dardiotis, Dimitrios P Bogdanos, To Keto or Not to Keto? A
Systematic Review of Randomized Controlled Trials Assessing the Effects
of Ketogenic Therapy on Alzheimer Disease, Advances in Nutrition, , nmaa073, https://doi.org/10.1093/advances/nmaa073

Intermittent fasting from dawn to sunset for 30 consecutive days is associated with anticancer proteomic signature and upregulates key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system and cognitive function in healthy subjects - ScienceDirect

https://www.sciencedirect.com/science/article/pii/S1874391920300130



Highlights

• First human serum proteomics study of 30-day intermittent fasting from dawn to sunset in healthy subjects 
• The 30-day intermittent fasting from dawn to sunset is associated with a serum proteome protective against cancer 
• Intermittent fasting from dawn to sunset for 30 days upregulates proteins protective against obesity, diabetes, and metabolic syndrome 
• Intermittent fasting from dawn to sunset for 30 days induces key regulatory proteins of DNA repair and immune system 
• Intermittent fasting from dawn to sunset for 30 days upregulates proteins protective against Alzheimer’s disease and neuropsychiatric disorders

Ketogenic diet activates protective γδ T cell responses against influenza virus infection | The Journal of Immunology

https://www.jimmunol.org/content/202/1_Supplement/62.7.abstract


"Ketogenic diet (KD) feeding resulted in an expansion of γδ T cells in the lung that improved barrier functions, thereby enhancing anti-viral resistance."
...
"Therefore, KD mediated immune-metabolic integration represents a viable avenue towards preventing or alleviating influenza disease."

Goldberg, E. L., Molony, R., Sidorov, S., Kudo, E., Dixit, V. D. & Iwasaki, A. (2019). Ketogenic diet activates protective γδ T cell responses against influenza virus infection. The Journal of Immunology, 202(1 Supplement), ss. 62.7-62.7. 

High-Fat and Ketogenic Diets in Amyotrophic Lateral Sclerosis (ALS)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438106/


"In summary, there are strong epidemiologic data showing that malnutrition is a common symptom of amyotrophic lateral sclerosis both in humans and in mice and may contribute to disease progression. There is also epidemiologic evidence that increased dietary fat and cholesterol intake might reduce the risk of amyotrophic lateral sclerosis and the rate disease progression. Finally, data from animal studies strongly suggest that increasing dietary intake of fat ameliorates disease progression (Paganoni & Wills
2013)."

Paganoni, S. & Wills, A. M. (2013). High-fat and ketogenic diets in amyotrophic lateral sclerosis. J Child Neurol, 28(8), ss. 989-992.
DOI:10.1177/0883073813488669

Alternative Fuels in Epilepsy and Amyotrophic Lateral Sclerosis (ALS)

https://www.ncbi.nlm.nih.gov/pubmed/27868154


"In both epilepsy and ALS, there are defects in glucose uptake and reduced tricarboxylic acid
(TCA) cycling, at least in part due to reduced amounts of C4 TCA cycle intermediates. In addition there are impairments in glycolysis in ALS. A reduction in glucose uptake can be addressed by providing the brain with alternative fuels, such as ketones or medium-chain triglycerides (Tefera et al. 2017)."


Alternative Fuels in Epilepsy and Amyotrophic Lateral Sclerosis. - PubMed - NCBI: Neurochem Res. 2017 Jun;42(6):1610-1620. doi: 10.1007/s11064-016-2106-7. Epub 2016 Nov 21.

Can ketogenic diet slow progression of ALS? - The Lancet Neurology

http://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(06)70462-8.pdf


"For the first time, researchers have shown that diet can alter the
progression of amyotrophic lateral sclerosis (ALS) in a mouse model of
the disease (Siva 2006)."


Can ketogenic diet slow progression of ALS?
Siva, Nayanah
The Lancet Neurology , Volume 5 , Issue 6 , 476

Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study | SpringerLink

https://link.springer.com/article/10.1007/s11011-017-0088-z



"Both diet groups showed significant improvement in ATEC and CARS scores in comparison to control group, yet ketogenic scored better results in cognition and sociability compared to GFCF diet group."



El-Rashidy, O., El-Baz, F., El-Gendy, Y. et al. Metab Brain Dis (2017). https://doi.org/10.1007/s11011-017-0088-z

Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes | SpringerLink

http://link.springer.com/article/10.1007/s10545-016-0011-5


Conclusion

Ketogenic diet was an effective and safe treatment for the majority of patients. Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.

Sofou, K., Dahlin, M., Hallböök, T. et al. J Inherit Metab Dis (2017). doi:10.1007/s10545-016-0011-5

Nutritional Ketosis Condition and Specific Ketogenic Diet, May Benefit Cancer Patients as an Alternative Treatment by Sudden Change in the Metabolic State of Cancer Cells. | Niknamian | International Science and Investigation journal

http://www.isijournal.info/journals/index.php/ISIJ/article/view/237

Abstract

Cancer disease is the second cause of death in the United States and world-wide. Most Researchers estimate that 595,690 of American people will die from cancer at the end of the year 2017. That means 1,600 deaths/day approximately.³⁹ Cancer in modern societies is commonly treated with the combination of organ surgery, chemotherapy and radiotherapy. Many kinds of diet strategies have been experimented. However, none of them have been particularly effective. Interestingly, there is some applied research suggesting that a very low-carb, high fat diet may help.^{40, 41, 42} According to Otto Warburg hypothesis, the cause of cancer is the change in the metabolism of mitochondrion in human cells. Low oxygen in tissues in combination with high blood glucose will change the cell respiration from aerobic to anaerobic which leads to fermentation type of respiration. In this perspective and prospective research, I have shown the very low carbohydrate ketogenic diet and mostly ketosis, may benefit cancer patients in reducing and weakening cancer cells. Although further researches are needed, this perspective article could be beneficial in future perspective of alternative treatments of cancer.




Niknamian, S. (2016). Nutritional Ketosis Condition and Specific Ketogenic Diet, May Benefit Cancer Patients as an Alternative Treatment by Sudden Change in the Metabolic State of Cancer Cells.. International Science And Investigation Journal, 5(5), 28-48. Retrieved from http://www.isijournal.info/journals/index.php/ISIJ/article/view/237

The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709725/



Abstract

Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists.



Storoni M, Plant GT. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis. Multiple Sclerosis International. 2015;2015:681289. doi:10.1155/2015/681289.

Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. - PubMed - NCBI

http://www.ncbi.nlm.nih.gov/m/pubmed/22840388/

CONCLUSION: "Preliminary data demonstrate that an insulin-inhibiting diet is safe and feasible in selected patients with advanced cancer. The extent of ketosis, but not calorie deficit or weight loss, correlated with stable disease or partial remission."


Nutrition. 2012 Oct;28(10):1028-35. doi: 10.1016/j.nut.2012.05.001. Epub 2012 Jul 26.

Metabolic characteristics of keto-adapted ultra-endurance runners - Metabolism - Clinical and Experimental

http://www.metabolismjournal.com/article/S0026-0495(15)00334-0/abstract?elsca1=etoc&elsca2=email&elsca3=0026-0495_201603_65_3_&elsca4=Genetics%7CEndocrinology%7CDiabetes%7CCardiology

Background

Many successful ultra-endurance athletes have switched from a high-carbohydrate to a low-carbohydrate diet, but they have not previously been studied to determine the extent of metabolic adaptations.

Conclusion

Compared to highly trained ultra-endurance athletes consuming an HC diet, long-term keto-adaptation results in extraordinarily high rates of fat oxidation, whereas muscle glycogen utilization and repletion patterns during and after a 3 hour run are similar.


DOI: http://dx.doi.org/10.1016/j.metabol.2015.10.028

FULL TEXT - A child with type 1 diabetes mellitus (T1DM) successfully treated with the Paleolithic ketogenic diet: A 19-month insulin freedom - International Journal of Case Reports and Images (IJCRI)

http://www.ijcasereportsandimages.com/archive/2015/012-2015-ijcri/CR-10582-12-2015-toth/ijcri-1058212201582-toth-full-text.php



"Conclusion: We opine that the Paleolithic ketogenic diet ensure normal glucose levels and can be maintained on the long-term in those patients with newly diagnosed T1DM with residual insulin secretion. It is important to emphasize, however, that in those patients with long-standing T1DM beta cells might have exhausted and therefore there may be a need for insulin replacement. In these cases, however, the Paleolithic ketogenic diet may be used as an adjunct in an attempt to likely prevent diabetic complications."




Tóth C, Clemens Z. A child with type 1 diabetes mellitus (T1DM) successfully treated with the Paleolithic ketogenic diet: A 19-month insulin freedom. Int J Case Rep Images 2015;6(12):753–758.