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Glutathione: the natural cellular defensor regulated by the diet


Glutathione (GSH) is a low molecular weight, antioxidant and the most abundant non-protein thiol in mammals, which plays an important role in peroxide detoxification, recycling of vitamins C and E and other biochemical reactions. It is synthesized from the amino acids glutamate, cysteine and glycine and most commonly found in its reduced form, GSH, which is consumed during redox reactions to produce the oxidized form, GSSG. Oxidative stress accelerates the oxidation rate of GSH to GSSG, thereby reducing the GSH/GSSG ratio; this change has important effects on cell signaling, disulphide exchange reactions with proteins and cell proliferation. Alterations in GSH homeostasis have been associated with protein energy malnutrition, cancer, Alzheimer’s and Parkinson’s diseases, AIDS, heart and liver disease, aging, diabetes and obesity. Due to the strong protective effects of GSH, it could be a therapeutic option to maintain cellular integrity and slow tissue degeneration in various diseases.

Notably, oral GSH supplementation had no effect on oxidative stress biomarkers or GSH concentrations in red blood cells isolated from healthy human subjects, a finding that may be attributable to GSH digestion. Furthermore, most cells are simply unable to absorb intact GSH, instead requiring it to be broken down into its constituent amino acids first. However, it is possible that dietary habits or specific diets can increase the synthesis of GSH in the cells of the human body. The mechanisms would be different, not only connected to the dietary intake of the amino acid precursors. It is known that certain plant constituents can induce cellular responses which result in the synthesis of enzymes and proteins with an antioxidant action. For example, carotenoids, polyphenols, other aromatic compounds and some vitamins form the basis of tumor “chemoprevention” interventions through food at the table.

The effect of Mediterranean diet

The Mediterranean diet (MedDiet) emphasizes high intake of extra virgin olive oil, lots of fruits, vegetables, grains, nuts, legumes, and legumes, and moderate intake of fish, dairy products, and red wine, while limiting the intake of eggs and processed foods. sweets. Typically no specific dose is recommended, but instead emphasis is placed on the frequency of food consumption. The effect of diet on oxidative stress levels has been investigated, given its high content of selenium, essential fatty acids, fiber and antioxidants. In fact, the rich intake of vegetables obtained with this diet guarantees the intake of significant quantities of polyphenols, phenolic acids and sulfur compounds, which could be able to improve the overall antioxidant cellular status. They would interfere with gene responses by inducing antioxidant proteins that scavenge reactive oxidant species (ROS).

Using data from the twin Heart Study, the researchers explored a potential association between MedDiet and GSH levels. MedDiet adherence, based on Mediterranean Diet Scores (MDS), showed an inverse association with plasma GSSG, resulting in higher GSH/GSSG ratios, independent of familial and genetic factors. Additionally, MedDiet has been shown to improve GSH peroxidase enzyme activity in patients with atrial fibrillation. In a cross-sectional study of healthy men and women, MDS was positively associated with plasma GSH levels, whereas similar diets, such as the Alternative Healthy Eating Index and the Diet to Stop Hypertension (DASH) diet, were not they were. These conclusions were independent of BMI, an important factor given the strong correlation between fat accumulation and increased total oxidative stress.

The effect of DASH diet

The DASH diet was developed in the 1990s and grew in popularity once the National Institutes of Health began supporting strong research into identifying dietary interventions that were effective against high blood pressure. The DASH diet includes the following servings of foods per day: 5 fruits and vegetables, 7 carbohydrates, 2 low-fat dairy products, no more than 2 lean meats, as well as 2-3 servings of nuts and seeds per week. The DASH diet emphasizes eating “healthy” carbohydrates (e.g., leafy green vegetables, whole grains, legumes) and “good” fats (e.g. foods low in saturated fat, nuts, avocados, fish). Because of these recommendations, the DASH diet has been called an excellent dietary intervention for people with other chronic conditions such as diabetes, heart disease, and obesity.

Patients with chronic disease often have altered GSH states and higher GSSG levels. When the DASH diet was implemented in overweight men and women with fatty liver for 8 weeks without other lifestyle modifications, plasma GSH concentrations increased significantly. Furthermore, total plasma GSH levels increased in overweight and obese women with polycystic ovary syndrome who adhered to the DASH diet for 8 weeks. In conclusion, the DASH diet appears to be a feasible dietary strategy for increasing total GSH levels. Frank obesity, such as endometriosis, diabetes and related disorders, in fact, are associated with a level of chronic subclinical inflammation which over time tends to deplete the normal cellular stocks of antioxidants, including GSH.

Other food styles influencing GSH

Naturally, vegetarian diets exclude meat, a significant source of amino acids required for GSH biosynthesis. However, vegetarian and vegan diets include substantial amounts of fruits and vegetables, which are naturally high in antioxidants, and these diets are associated with lower rates of obesity, cancer and diabetes. A vegetarian diet appears to positively influence GSH levels in some populations, such as patients with type 2 diabetes and cardiovascular disease. The richness of polyphenols, aromatic acids and other antioxidants of a vegetarian diet is largely responsible for these positive effects. However, other studies have found no significant differences in GSH status between vegetarians or meat or fish eaters.

A low-protein vegan diet leads to significantly lower blood GSH levels than omnivores and lacto-ovo vegetarians. This could be due to a lower introduction of glutamine and cysteine, two fundamental building blocks of GSH abundant in eggs, cheeses and dairy products and in whey itself. A Western-style diet is characterized by high amounts of meat, saturated fat, refined grains and sugar, with low amounts of fruits and vegetables. The Western diet has been associated with an increased risk of cancer and other chronic diseases and is commonly used to experimentally induce oxidative stress and antioxidant depletion, including impaired GSH synthesis.

Furthermore, Western-style diets correlated with low levels of vitamin B6, methionine, cysteine, and lysine, as well as high homocysteine levels, suggesting that the diet may affect GSH homeostasis through its effects on precursor availability. We are increasingly seeing the introduction of a scarce vegetable side dish in “fast food” dishes, but they will never be able to compete with the freshness of a healthy natural and unprocessed dish. The Western diet, overall, is associated with overweight, insulin resistance, and type 2 diabetes, so alternative nutrition emphasizing fresh foods is recommended for better overall health.

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Pirouzeh R et al. Diab Metab Syndr. 2020; 14(6):2131.

Paschalis V et al. Free Rad Biol Med. 2018; 115.

Bettermann EL et al. J. Nutr. 2018; 148, 245-53.

Honda Y et al. BMC Gastroenterol. 2017; 17:96.

Razavi Zade M et al. Liver Int. 2016; 36:563-71.

Mukwevho E et al. Molecules 2014; 19:19376.


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Dott. Gianfrancesco Cormaci
Dott. Gianfrancesco Cormaci
Laurea in Medicina e Chirurgia nel 1998, specialista in Biochimica Clinica dal 2002, ha conseguito dottorato in Neurobiologia nel 2006. Ex-ricercatore, ha trascorso 5 anni negli USA alle dipendenze dell' NIH/NIDA e poi della Johns Hopkins University. Guardia medica presso la casa di Cura Sant'Agata a Catania. In libera professione, si occupa di Medicina Preventiva personalizzata e intolleranze alimentari. Detentore di un brevetto per la fabbricazione di sfarinati gluten-free a partire da regolare farina di grano. Responsabile della sezione R&D della CoFood s.r.l. per la ricerca e sviluppo di nuovi prodotti alimentari, inclusi quelli a fini medici speciali.

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