In a recent study published in scientific report, Researchers used a mouse (A/J mouse) model to evaluate the anticancer effects of different oils consumed as part of a ketogenic diet (KD).
Specifically, they compared seven commonly consumed fat-rich KDs to a Western-style diet and a 15% carbohydrate diet as a control.
The results demonstrated that all ketogenic diets were superior to Western and 15% carbohydrate diets in preventing nicotine-derived nitrosamine ketone (NNK)-induced lung cancer in mice.
study: A fish oil-enriched ketogenic diet is superior to other fats in preventing NNK-induced lung cancer in A/J mice. Image credit: Natalia Klenova/Shutterstock.com
background
This study highlights the anti-lung cancer potential of fish oil (FO). Fish oil was found to increase plasma β-hydroxybutyrate (β-HB), lower blood glucose, and attenuate fatty acid synthase (FAS) expression, thereby blocking lung tumor metabolism. Formation of nodules.
Of note, to address KD-induced high plasma triglyceride (TG) and cholesterol levels, researchers further characterized the effects of long-term ketogenic diets on lipid profiles and liver health, and compared standard Not only did KD not induce liver damage, FO-enriched KD was even less toxic to the liver and lipid profile, proving its safety.
What is a ketogenic diet and how can it help against cancer?
The ketogenic diet (KD) is a dietary therapy first developed in the 1920s to treat intractable epilepsy. They are characterized by a very high fat content and low carbohydrate content (CHO), and the body must metabolize fat for energy.
Most KDs are designed to provide 90% of their total calories from fat, while only 2% of their calories come from CHO. KD adapts the body to rely on KD-derived ketone bodies instead of glucose.
Ketone bodies have been a source of recent scientific excitement because most cancerous tumors cannot utilize them as a fuel source.
Surprisingly, systematic evaluation of KD-related fats is still lacking. Still, scientists hypothesize that differences in the fatty acid content of these fats may result in significantly different growth profiles for tumor cells.
Previous studies by our research team have shown that reducing easily digestible CHO from 50% (typical CHO content in Western diets) to 15% reduced nicotine-derived nitrosamine ketone (NNK)-induced tumor nodules in A/J mice. It has been proven that there is a significant reduction in , further supports the need to investigate the benefits of alternative diets rich in fat and low in CHO as cancer prevention interventions.
“…saturated fatty acids, such as palmitic acid, the most common dietary fatty acid, are potent activators of Toll-like receptor 4 (TLR4) signaling within macrophages and promote inflammation. Omega-6 fatty acids such as arachidonic acid (AA) are known to be metabolized to prostaglandin E.2 (PGE2), prostanoids have been shown to aid tumor growth both directly and through suppression of anti-tumor immunity. On the other hand, omega-3 fatty acids have been shown to have anti-inflammatory effects, at least in part by inhibiting the conversion of AA to PGE.2.”
About research
In this study, researchers compared the anti-NKK-induced lung cancer effects of three different diets: a Western diet (50% CHO), a 15% amylose diet (in-house developed, 50% fat-based). , KD (7 types, each with a different fat source).
The seven KDs are Western fat (standard KD), medium chain fatty acids (MCT-KD), milk fat (MF-KD), palm oil (PO-KD), olive oil (OO-KD), and corn oil (CO- KD), fish oil (FO-KD).
All experiments were performed in 12-week-old female A/J mice. Data collection included blood glucose levels (measured during night feedings), blood and plasma biochemical analysis (plasma β-hydroxybutyrate). [β-HB]cholesterol, and alanine aminotransferase levels), and immunohistochemistry of resected and preserved lung and liver tissue.
It is hypothesized that long-term dependence on KD can alter lipid profiles and damage the liver, so researchers compared various We further investigated KD liver health scores (by surrogate indicators and biomarkers).
Liver health assessment uses thiobarbituric acid substances (TBARS) assay to determine liver TBARS levels, enzyme-linked immunosorbent assay (ELISA) to determine liver 8-OHdG, and whole liver sections were scored for nonalcoholic fatty liver. Disease (NAFLD).
Finally, in an attempt to elucidate the mechanistic basis of the anticancer potential of KD (particularly fat), mouse fecal samples were used for microbiome analysis.
research result
Five months of dietary intervention after NNK injection revealed that the Western diet was the worst (mean number of nodules = 18). In contrast, 15% of the amylose diet showed an average of only 10 nodules.
KD (even standard KD with common Western dietary fat) performed much better than both diets. Notably, FO-enriched KD was found to perform best and was the only his KD cohort with significantly different nodule numbers from standard KD.
Investigation of the mechanisms supporting these observations revealed that FO-KD produces substantially more ketone bodies than other KD cohorts.
In parallel, KD was shown to downregulate and attenuate fatty acid synthase (FAS) expression in the liver and increase CPT1a levels. Remarkably, fish oil enrichment further accentuated these results.
This suggests that improved ketosis may contribute to the anticancer properties of FO-KD. FO-KD was further observed to reduce the levels of inflammatory cytokines such as interleukin-6 (IL-6) and PGE.2mouse lung.
“Interestingly, KD enriched with palm and corn oils may further reduce IL-6 levels, casting doubt on the long-held notion that palm and corn oils promote inflammation. PO-KD and CO-KD had the highest IFNγ levels and the lowest IL-5 and IL-10 levels among the different KDs. Unexpectedly, FO-KD was found to be effective in preventing lung nodule formation. Although most effective, this diet had no specific effects on the pro-inflammatory cytokines/chemokines tested, apart from a trend towards higher IL-1β levels.”
Immunohistochemistry results validate these assays and show that FAS, which has significantly lower KD than Western diet (lowest FO-KD), plays the most important role in NNK-induced lung pathology. suggests that it is possible.
Encouragingly, liver health assays debunk previously hypothesized concerns, showing that not only is KD less damaging than a standard Western diet or a 15% amylose diet, but FO-KD and MCT- It was revealed that KD was found to cause even less liver damage than these.
In contrast, standard KD did not significantly alter the lipid profile compared to Western or amylose diets, whereas FO-KD and MCT-KD reduced low-density (LDL) and very low-density (LDL) in mouse plasma. significantly increased density lipoprotein (VLDL) levels.
conclusion
This study verified the long-term safety of KD on liver health and verified the anti-lung cancer properties of KD in A/J mice.
Fish oil was found to be the most effective of all the KD fats tested and is thought to confer anti-cancer protection through metabolic changes, particularly by reducing FAS levels.
These findings highlight FO-KD as a future intervention for lung cancer, but cardiovascular safety must first be confirmed before implementing these interventions.
