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Ketogenic food plan: A metabolic makeover boosting immunity and battling inflammation

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Ketogenic food plan: A metabolic makeover boosting immunity and battling inflammation

Western dietary (WD) habits are known to cause a lot of today’s non-communicable diseases by promoting chronic inflammation. Recently, to counteract WD-induced metaflammation, ketogenic diets (KD) have emerged.

Given the drastic change in nutrient composition during KD, it is cheap to hypothesize large-scale changes within the human metabolome. Moreover, this alteration within the metabolome could also result in changes in immunity.

A recent Clinical Nutrition study discusses alterations within the human metabolic fingerprint related to KD.

Study: A ketogenic food plan substantially reshapes the human metabolome. Image Credit: nadianb / Shutterstock.com

Background

WD entails the excessive intake of ultra-processed food with high quantities of sugar and refined carbohydrates. This food plan has been linked to the event of assorted diseases, akin to diabetes and obesity.

Previous research has shown that the excessive consumption of carbohydrates triggers aberrant activation of the NLRP3 inflammasome. This results in the next secretion of pro-inflammatory cytokines and, in consequence, contributes to most recent non-communicable diseases.

Comparatively, KD involves a minimal intake of carbohydrates and results in the hepatic synthesis of ketone bodies, thereby providing a sturdy alternate source of energy to the body’s peripheral tissues. One variety of ketone body generally known as β-hydroxybutyrate (BHB) serves as a substrate for mitochondrial oxidative phosphorylation (OXPHOS) and results in pleiotropic effects.

Recent research has shown that KD significantly bolsters human CD4 and CD8 T-cell immune capability and the differentiation of regulatory and memory T-cells. These observations could indicate that the consequences of KD on T-cell immunity may evoke marked changes to the human serum metabolite composition.

In regards to the study

Forty healthy adult volunteers were recruited to take part in a three-week ad-libitum KD for a prospective dietary intervention study. Firstly (T0) and end of the study (T1), urine analyses and untargeted mass spectrometric metabolome analyses of the tryptophan pathway were performed. Serum metabolites were also quantified.

Prior to the beginning of the study, participants consumed a typical WD comprising about 55-60% carbohydrates, 25-30% fat, and 10-15% protein. Within the KD, a maximum of 10% of the each day caloric intake was provided by carbohydrates, whereas the remaining food plan consisted of 60-70% fat, 20-30% protein, and 10% carbohydrates.

All participants accomplished the study and reported sufficient levels of ketone bodies throughout the dietary intervention course.

Key findings

Even a short-term KD of three weeks fundamentally reshaped the human metabolome. In reality, the metabolic regular state adjusted rapidly towards the production and utilization of ketone bodies. This evaluation also showed improved insulin and triglyceride levels and better quantities of metabolites controlling mitochondrial protection and anti-inflammation.

The marked reduction of carbohydrates led to a discount in each insulin and c-peptide levels, which can explain the moderate weight reduction observed within the participants. It couldn’t be confirmed whether the extent of weight reduction correlated with the changes in serum metabolic parameters.

The fasting serum glucose concentration remained stable, whereas increased urea levels may very well be because of enhanced protein metabolism. Concentrations of alanine, glucogenic amino acid (AA) proline, and glutamine were markedly reduced, while leucine, isoleucine, and branched-chain AA (BCAA) valine showed higher abundances.

Higher fat consumption improved the serum lipid profiles of the participants. Importantly, a profound upregulation of each acylcarnitines and free fatty acids was observed.

During KD, high acylcarnitines imply the next demand for long-chain fatty acids as substrates of β-oxidation. Using carnitine as a transport shuttle system, these substances should be transported into the mitochondrial matrix.

Linoleic acid (ω-6), linolenic acid (ω-3), docosahexaenoic acid (DHA), and eicosatetraenoic acid (ETA) levels were significantly elevated. This observed shift could contribute to the dampening of innate inflammation.

KD significantly shifted the metabolism of tryptophan towards kynurenic acid and kynurenine while attenuating the synthesis of quinolinic acid. Kynurenic acid has been shown to exert protective effects on mitochondrial respiration, while quinolinic acid is related to mitochondrial dysfunction. Due to this fact, greater OXPHOS is supported by improved mitochondrial protection.

Conclusions

The present study demonstrated that even after a brief period of KD, significant changes in metabolite composition could occur. These changes could have a helpful impact on each immune cell fate and metabolic programming beyond ketone effects. No metabolic risk aspects were identified.

Based on the findings, it may very well be concluded that KD is a useful therapeutic and preventive immunometabolic tool, not less than within the short- and medium-term. Nevertheless, more research is required to find out whether KD produces similar helpful effects in the long term and whether short-term KD could provide lasting metabolic advantages.

Journal reference:

  • Effinger, D., Hirschberger, S., Yoncheva, P., et al. (2023) A ketogenic food plan substantially reshapes the human metabolome. Clinical Nutrition. doi:10.1016/j.clnu.2023.04.027

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