Cancer as a Metabolic Disease: Implications for Novel Therapeutics

Seyfried, T. N.

doi:10.1158/aacr.edb-13-7962

Cited by 32 publications

(47 citation statements)

References 147 publications

(214 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, KD improved rotarod performance in young (1-2 month) non-transgenic and APP +PS1 mice when fed on a KD for one month [35], while no effects on the soluble amyloid in brain or muscle could be detected by ELISA, in agreement with a previous study [36]. Additionally, it has been extensively reported that ketosis may be beneficial against cancer by decreasing blood glucose levels, the primary metabolic fuel for cancer cells [4,5]. In fact, previous work highlighted that blood ketone concentration was negatively correlated with tumor growth [37].…”

supporting

confidence: 86%

“…However, the brain is not capable to obtain significant energy from FFAs, thus hepatic ketogenesis converts them into ketone bodies: β-Hydroxybutyrate (BHB) and acetoacetate (AcAc), while a percentage of AcAc spontaneously decarboxylates to acetone [1]. To date, it has been broadly demonstrated how the metabolic state of mild ketosis, which can be induced through KD administration, calorie restriction or fasting, represents a valid tool for the metabolic management of epilepsy and a number neurodegenerative diseases [2], Amyotrophic Lateral Sclerosis (ALS) [3], and some types of cancer [4,5]. In addition, nutritional treatments represent an effective alternative where pharmaceutical approaches fail or produce unbearable side effects and costs for public health worldwide.…”

Section: Editorialmentioning

confidence: 99%

See 1 more Smart Citation

The Ketogenic Diet Approach as Metabolic Treatment for a Variety of Diseases

Pilla¹

2016

J Epilepsy

View full text Add to dashboard Cite

EditorialHuman brain derives over 60% of its energy from ketones when glucose availability is limited. After prolonged periods of fasting or Ketogenic Diet (KD), the whole body utilizes energy obtained from Free Fatty Acids (FFAs) released from adipose tissue. However, the brain is not capable to obtain significant energy from FFAs, thus hepatic ketogenesis converts them into ketone bodies: β-Hydroxybutyrate (BHB) and acetoacetate (AcAc), while a percentage of AcAc spontaneously decarboxylates to acetone [1]. To date, it has been broadly demonstrated how the metabolic state of mild ketosis, which can be induced through KD administration, calorie restriction or fasting, represents a valid tool for the metabolic management of epilepsy and a number neurodegenerative diseases [2], Amyotrophic Lateral Sclerosis (ALS) [3], and some types of cancer [4,5]. In addition, nutritional treatments represent an effective alternative where pharmaceutical approaches fail or produce unbearable side effects and costs for public health worldwide. However, before analyzing how benefits from therapeutic ketosis could be exploited, let us mention some pivotal concepts about metabolism. Under normal conditions and mostly in western societies, a healthy brain utilizes glucose as primary energy source, which unbalance can lead to a number of neurodegenerative disorders often associated with mitochondrial impairment and glucose transport-related dysfunctions, such as in epilepsy, Traumatic Brain Injury (TBI), Parkinson's and Alzheimer's diseases [6,7]. Ketone bodies and Krebs cycle intermediates represent the best fuels for brain and other organs. In fact, through their utilization, impaired glucose metabolism may be bypassed and their neuroprotective properties may be exploited [8]. However, neuroprotective mechanisms of ketosis are currently object of studies as mechanisms of action are still not sufficiently understood. It has been shown that ketone bodies are neuroprotective as they induce a consistent increase in mitochondrial biogenesis regulating the synaptic function, and also generate ATP increases, thus reducing the reactive oxygen species production in neurological tissues [9,10], and notably inhibit superoxide synthesis in primary rat neuronal cultures exposed to hyperoxia [11]. Moreover, the main reason why the KD has been proven so effective as an anticonvulsant aFpproach is because it significantly reduces the metabolism of glucose [12]. In addition, Ma and colleagues [13] demonstrated that, at physiological concentrations, BHB and AcAc reduce spontaneous discharges of GABAergic neurons in the rat substantia nigra, through ATP-sensitive potassium channels.Also, a reduction of total CNS aspartate levels in association with an increase of glutamate concentrations was found during ketosis, observing a significant increase of decarboxylated glutamate to GABA, the main inhibitory neurotransmitter [14,15]. Moreover, a remarkable increase in mitochondrial transcription enzymes and proteins was observed in rat hippocampus after the...

show abstract

supporting

confidence: 86%

Section: Editorialmentioning

confidence: 99%

The Ketogenic Diet Approach as Metabolic Treatment for a Variety of Diseases

Pilla¹

2016

J Epilepsy

View full text Add to dashboard Cite

show abstract

“…Altered energy metabolism is proving to be as widespread in cancer cells as many of the other cancer-associated traits that have been accepted as hallmarks of cancer. 28 The regulation of metabolism, relevant to senescence process, 29 would be a key to improve as well as to identify new anticancer therapies in the future.…”

Section: The Methodology Of Workmentioning

confidence: 99%

On the relationship between aging & cancer

Ja¹,

Mansilla²,

Cocho³

et al. 2018

MOJGG

View full text Add to dashboard Cite

“…In addition, more and more studies suggest that obesity may also increase the risk of poor prognosis for patients with certain cancers [4]. Cancer has traditionally primarily been viewed as a disorder of proliferation but has today been suggested to be also considered as a metabolic disease [5,6]. This suggestion was primarily based on the notion of cancer-associated metabolic changes on a tissue (tumor) level [6].…”

Section: Introductionmentioning

confidence: 99%

Obesity and Risk of Cancer: An Introductory Overview

Pischon

Nimptsch

2016

Obesity and Cancer

View full text Add to dashboard Cite

The prevalence of obesity has increased substantially in the past in almost all countries of the world, and a further increase is expected for the future. Besides the well-established effects on type 2 diabetes and cardiovascular disease, there is convincing evidence today that obesity also increases the risk of several types of cancer, including colorectal cancer, postmenopausal breast cancer, endometrial cancer, renal cell carcinoma, esophageal adenocarcinoma, pancreatic cancer, and liver cancer. Obesity probably also increases the risk of ovarian cancer, advanced prostate cancer, gallbladder cancer, and gastric cardia cancer. For some cancer types there is also some evidence that weight gain during adulthood increases cancer risk, e.g., colorectal cancer, postmenopausal breast cancer, endometrial cancer, and liver cancer. However, for most cancers it is an open question as to whether vulnerability to weight gain in relation to cancer risk depends on specific life periods. There are a number of plausible mechanisms that may explain the relationship between obesity and cancer risk, including pathways related to insulin resistance, inflammation, and sex hormones. For most cancers there is only limited evidence that weight loss in adulthood decreases cancer risk, which is primarily due to the limited long-term success of weight loss strategies among obese individuals.There is limited evidence suggesting that obesity may also be associated with poor prognosis among patients with colorectal cancer, breast cancer, endometrial cancer, ovarian cancer and pancreatic cancer. Taken together, these findings support efforts to prevent weight gain on an individual level as well as on a population level. Whether and to what extent overweight or obese cancer patients benefit from weight loss strategies is unclear and a matter of debate.

show abstract

Cancer as a Metabolic Disease: Implications for Novel Therapeutics

Cited by 32 publications

References 147 publications

The Ketogenic Diet Approach as Metabolic Treatment for a Variety of Diseases

The Ketogenic Diet Approach as Metabolic Treatment for a Variety of Diseases

On the relationship between aging & cancer

Obesity and Risk of Cancer: An Introductory Overview

Contact Info

Product

Resources

About