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Clinical nutrition: minerals, vitamins and other natural bioactives to treat current medical issues

Introduction

Vitamins and trace elements, collectively known as micronutrients, are vital for basic metabolic reactions in the human body. The deficiency of micronutrients or even increased amounts could lead to serious health disorders. Research has revealed that long-term abnormal levels of micronutrients could be associated with the etiopathogenesis of some common neurological diseases. Chronic and acute alterations in micronutrient levels could also lead to serious complications in neurological diseases. Water-soluble vitamins (B complex and C) are not stored in the body, but fat-soluble vitamins (A, D, E, K) are; and a lack of fat-soluble vitamins may manifest later. Micronutrients like minerals (and most vitamins as well) mainly act as catalysts in enzyme systems. Other essential roles include modulation of cellular immunity, antioxidant activity, and wound healing. Micronutrients can neutralize free radical reactive nitrogen species (RNS) and reactive oxygen species (ROS). They modulate cellular immunity and tissue healing either directly or indirectly by using substances created through their induction.

Micronutrients in clinical practice

It is common for symptoms of micronutrient deficiency to appear after long-lasting depletion. These symptoms range from skin manifestations and frequent infections to serious deficiencies like osteomalacia (vitamin D) and scurvy (vitamin C). Long-lasting deficiencies can manifest acutely or via lactic acidosis development. Capillary leakage increases in pathological conditions due to the influence of released cytokines. Subsequently, the plasma level of all micronutrients decreases. Owing to the fact that the concentration of micronutrients with antioxidant effects is highest at the site of inflammation, redistribution mechanisms are also involved. It should be noted that there is an increase in the loss of micronutrients with drainages, urine, repeated hemodialysis and burn victims. The reduction in micronutrient plasma levels is a guess rather than a real detection. The levels of only a small number of micronutrients can be assessed routinely. This micronutrient dilemma raises several questions.

Micronutrient administration: to whom and how?

Administration is recommended for hospital patients admitted to the intensive care unit (ICU). Such patients have oxidative stress, redistribution, and increased usage. Patients receiving repeated hemodialysis and those with burns, exudates, and wound areas are also candidates for fortification. In patients with home parenteral nutrition (HPN), special attention is required during substitution. The enteral route is the most natural route for administration, either in an ordinary meal or defined enteral nutrition by gastrostomy or using a nasogastric/nasojejunal tube. In supplying micronutrients through this route, we should consider the principles of absorption of individual micronutrients. An increase in the quantity of one could preclude the absorption of a different one.

As an example, the greater intake of iron reduces the resorption of copper (Cu) and zinc (Zn). The depletion of Copper then manifests as microcytic anemia. Sometimes, synergies can be detected with regard to absorption. As an example, the administration of vitamin C increases the absorption of iron. However, the limited absorption capacity of the gastrointestinal tract (vitamin C) must be considered. In critically ill patients and in patients with malabsorption, the whole quantity of micronutrients in a given amount of enteral nourishment is not absorbed completely. The parenteral route is another option for the administration of micronutrients. This is particularly useful when using a range of pharmaceutical mixtures. There is another important issue not to be forgotten: gut dysbiosis.

Many clinical condition, genetic or not, are often associated with imbalance in gut microbial community, better known as microbiota. The problem is often worsen by a previous poor lifestyle (e.g. poor feeding, tobacco or alcohol abuse, etc.). This “guest” is noowadays unequivocally recognized as the “master regulator” of our health. Immune system, brain cognition, liver metabolism and other bodily functions are tightly regulated by microbiota in a either direct or indirect way. In chronic conditions, epsecially concerning elder patients, probiotic (i.e. Lactobacillus and Bifidobacterium strains) should be a priority of treatment and supplemntation even before to start any HPN. THis because an imbalance in microbiota composition may severely preclude the absorption of many nutrients by the gut mucosa.

Micronutrients in some neurological disorders

In Alzheimer’s disease (AD) and Parkinson’s disease (PAD), supplementation with Vitamins A, C, D, E, Folic Acid, Selenium, and Zinc brings about benefits proven by research. For AD, Homocysteine (Hcy), 25-OH vitamin D, Cu, and Zn should be monitored, while for PAD, it is important to monitor B6, 25-OH vitamin D, vitamin E and Hcy. In both cases, a diet rich in antioxidants can be used as an adjuvant therapy. In Amyotrophic lateral sclerosis (ALS), 25-OH-vitamin D and vitamin E should be monitored, and supplementation with Vitamins E, D, C and B-complex is recommended as well.

In Wilson’s disease, FD Zinc (Zn) should be supplemented (despite is a natural antagonsit of copper accumulation), diets rich in antioxidants should be used as adjuvant therapy, and Cu, Zn, and ceruloplasmin should be monitored. For Huntington’s disease, 25-OH-vitamin D should be monitored, and supplements with proven benefits are Coenzyme Q10, vitamins A, D, E, C, B1, B3, biotin, Se and Zn (pyruvate). Vitamin D supplementation is beneficial in myasthenia gravis; and vitamins A, D, and E are recommended in Multiple sclerosis as well.

Nutrients against nowadays plague: obesity

Food and nutrition are the primary focuses of obesity therapy since maintaining a healthy weight can be difficult. To prevent obesity, one must continue to modify their intake of nutrients, including protein and legumes, as well as oligosaccharides, polysaccharides, and fiber. Another approach is incorporating vital nutrients into the diet instead of lowering the energy associated with a limited amount of food items. Encouraging healthy living practices requires more physical activity that reduces calorie intake and fat content. Dietary interventions containing plant-based bioactive compounds have become a promising therapeutic approach for treating obesity mainly because of avoiding adverse side effects caused by anti-obesity drugs. Many studies have been conducted to investigate the anti-obesity effects of these phytonutrients.

Polyphenols

Polyphenols are the most abundant bioactive phytonutrients found in plants. Mechanistically, polyphenols prevent obesity by inhibiting adipocyte differentiation, regulating lipid metabolism, inhibiting appetite and modulating gut microbiota. Evidence indicates that Epigallocatechin gallate (EGCG) from green tea extracts reduces lipid accumulation by inhibiting adipocyte differentiation and stimulating the conversion of white adipocytes into brown adipocytes. In clinical trials, consumption of green tea extract-enriched bread has been found to reduce waist circumference and maintain normal blood pressure.

Anthocyanins are plant-derived color pigments with anti-inflammatory and anti-obesity properties. These compounds exert anti-inflammatory effects by preventing the activation of NF-κB transcription factor, which regulates inflammatory cytokines. Evidence indicates that anthocyanins improve gut dysbiosis, prevent lipid accumulation, reduce weight gain, and control obesity. Cyanidin 3-glucoside derivatives have been found to reduce obesity-induced inflammation by inhibiting adipocytokine (es. visfatin, adiponectin, resistina, IL-6, ecc.) secretion as well. These derivatives have been found to prevent obesity by stimulating energy expenditure and regulating lipid metabolism.

Curcumin has been found to prevent lipid accumulation by increasing lipolysis, preventing fatty acid synthesis, and increasing mitochondrial fatty acid oxidation.Muscadine grape and muscadine grape wine contain a large number of polyphenols and polysaccharides, which can effectively reduce body weight and prevent lipid accumulation by increasing antioxidant levels, reducing leptin levels, preventing fatty acid absorption, and inhibiting pro-inflammatory mediators.

Phlorizin is a phytonutrient found in apples. The combination of phlorizin and other strategies has been used to prevent body weight gain and reduce fat accumulation. Mechanistically, phlorizin has been found to suppress enzymes associated with fat production and storage and cholesterol synthesis. Overconsumption of fatty foods alters gut microbiota composition by reducing beneficial bacterial populations. Evidence indicates that phlorizin helps prevent obesity by maintaining gut microbiota composition and intestinal barrier integrity.

Gallic acid is a phenolic acid derived from vegetables and fruits like berries and pomegranate. Evidence indicates that gallic acid reduces lipogenesis and fat accumulation by activating the AMPK/SIRT1/PGC-1 pathway. Moreover, gallic acid has been found to reduce the size of adipocytes in obese mice. However, studies involving obese human participants have shown that gallic acid cannot reduce body weight and food intake mainly because of its low bioavailability in blood.

Resveratrol and Quercetin

A combination of resveratrol and quercetin has been found to be effective in reducing body weight gain, adipocyte size, and adipose tissue weight and improving dyslipidemia. These phytonutrients can significantly reduce high-fat diet-induced obesity and inflammation by activating the AMP-activated protein kinase/sirtuin 1 (AMPKα1/SIRT1) signaling pathway. The combination of resveratrol and quercetin has also been found to inhibit adipogenesis by reducing gene expression of key adipogenic factors and reducing levels of adipokines, adipsin, and glycolysis-related enzymes.

Alkaloids

Alkaloids are nitrogen-containing compounds that can be divided into many sub-classes depending on their precursors. Alkaloids exert anti-obesity effects by increasing lipolysis and thermogenesis and reducing appetite. Evidence indicates that alkaloids inhibit adipocyte differentiation by downregulating transcription factors like PPAR, SREPB-1c and C-EBP proteins, which are master regulators of this process. The alkaloid Cinchonine has been found to reduce adipogenesis by downregulating the WNT and galanin-mediated signaling pathways. Other alkaloids, such as lansiumamide B and mahanimbine, have shown anti-obesity effects by inhibiting adipogenesis, preventing hyperlipidemia and fat accumulation, and reducing inflammation and oxidative stress.

Terpenoids

Terpenoids are the largest secondary metabolites mostly found in essential oils. Carotenoids are tetraterpene pigments with anti-obesity properties. These metabolites are known to interfere with nuclear receptors to suppress adipocyte development. Lycopene is also known to prevent obesity by increasing the browning of white adipose tissue, upregulating the expression of thermogenic genes, and reducing the expression of fibroblast growth factors (FGF21). Saponins are triterpene glycosides with several bioactive properties. Panax ginseng, Panax japonicas and Platycodi radix are the most widely known saponin sources with proven efficacy in reducing obesity.

New sources and techs for food supplements

The utility of phytonutrients can be maximized by using their byproducts and waste products. Many kind of fruit peels and seed wastes (pomaces), are recognized as a precious bio-mine. Many phytonutrient-rich parts of plants, such as peels, stems, and leaves, are discarded as waste products. Bioactive compounds present in these waste products can be used to develop healthy food supplements; many novel factories now are equipped for working this through. Innovative food processing technologies can be implemented to extract these bioactive compounds and incorporate them into regional diets to improve nutritional value.

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

Scientific references

Goya L, de Pascual TS. Nutrients 2023; 15:4134.

Siddiqui SA et al. Foods. 2023 Sept 28; 12(9):3610.

Luo Y et al. Biomed Pharmacother. 2023; 165:115274.

Saad B. Int J Mol Sci. 2023 Aug 10; 24(16):12641.

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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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