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      The effects of twenty-four nutrients and phytonutrients on immune system function and inflammation: A narrative review

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          Abstract

          Background and Aim:

          Recently, optimal immune function has become a primary focus of worldwide attention not only in the prevention of chronic disease but also as one strategy to reduce the severity of acute illness. Inflammation, a process largely controlled by the immune system, has long been studied and recognized for its role in chronic disease. Optimizing immune function or managing inflammation using individual nutrients and phytonutrients is not well understood by the average person. Thus, this narrative literature review summarizes many of the more recent findings about how certain nutrients and phytonutrients affect immune function and inflammation, and how they may best be utilized considering the growing worldwide interest in this topic.

          Methods:

          A comprehensive literature search of PubMed was performed to find clinical trials in humans that assessed the effect of nutrients and phytonutrients on immune function and inflammation, in individuals with acute and chronic health conditions, published in English between 2000 and 2020. Two independent reviewers evaluated the articles for their inclusion.

          Results:

          Eighty-seven articles were summarized in this narrative review. In total 24 nutrients and phytonutrients were included in the study, that is, acetyl-L-carnitine, Aloe vera polysaccharides, beta-glucans, bilberry, black seed oil, coenzyme Q10, curcumin (turmeric), frankincense, garlic, ginger, hydrolyzed rice bran, isoflavones, lipoic acid, mistletoe, N-acetyl cysteine, omega-3 fatty acids, resveratrol, selenium, shiitake mushroom and its derivatives, Vitamin B12, Vitamin C, Vitamin D3 (cholecalciferol), Vitamin E (d-alpha- and gamma-tocopherol), and zinc. Some of the noteworthy immune function and anti-inflammatory responses to these interventions included modulation of nuclear factor-Kappa B, tumor necrosis factor-a, interferon-g, interleukin-6, and CD4+ T cells, among others. These findings are not completely consistent or ubiquitous across all patient populations or health status.

          Conclusions:

          Based on this review, many nutrients and phytonutrients are capable of significantly modulating immune function and reducing inflammation, according to multiple biomarkers in clinical trials in different populations of adults with varying health statuses. Thus, dietary supplementation may serve as an adjunct to conventional pharmaceutical or medical therapies, but evaluation of risks and benefits for each person and health status is necessary. Additional larger studies are also needed to investigate the safety and efficacy of nutritional compounds in various health conditions, with emphases on potential drug-supplement interactions and clinical endpoints.

          Relevance for Patients:

          As demonstrated in the reviewed clinical trials, patients of various health challenges with a wide range of severity may benefit from select nutrients and phytonutrients to improve their immune function and reduce inflammation.

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          Most cited references365

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          Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017

          Summary Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries—Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5–23·9), representing an additional 7·61 million (7·20–8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0–8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0–24·0) and the death rate by 31·8% (30·1–33·3). Total deaths from injuries increased by 2·3% (0·5–4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2–15·1) to 57·9 deaths (55·9–59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000–289 000) globally in 2007 to 352 000 (334 000–363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8–148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2–40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2–36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990—neonatal disorders, lower respiratory infections, and diarrhoeal diseases—were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Funding Bill & Melinda Gates Foundation.
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            A role for mitochondria in NLRP3 inflammasome activation.

            An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host 'danger', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we show that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome. Resting NLRP3 localizes to endoplasmic reticulum structures, whereas on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters. Notably, both ROS generation and inflammasome activation are suppressed when mitochondrial activity is dysregulated by inhibition of the voltage-dependent anion channel. This indicates that NLRP3 inflammasome senses mitochondrial dysfunction and may explain the frequent association of mitochondrial damage with inflammatory diseases.
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              Type 2 diabetes as an inflammatory disease.

              Components of the immune system are altered in obesity and type 2 diabetes (T2D), with the most apparent changes occurring in adipose tissue, the liver, pancreatic islets, the vasculature and circulating leukocytes. These immunological changes include altered levels of specific cytokines and chemokines, changes in the number and activation state of various leukocyte populations and increased apoptosis and tissue fibrosis. Together, these changes suggest that inflammation participates in the pathogenesis of T2D. Preliminary results from clinical trials with salicylates and interleukin-1 antagonists support this notion and have opened the door for immunomodulatory strategies for the treatment of T2D that simultaneously lower blood glucose levels and potentially reduce the severity and prevalence of the associated complications of this disease.
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                Author and article information

                Journal
                J Clin Transl Res
                J Clin Transl Res
                Whioce Publishing Pte. Ltd.
                Journal of Clinical and Translational Research
                Whioce Publishing Pte. Ltd.
                2382-6533
                2424-810X
                27 May 2021
                26 June 2021
                : 7
                : 3
                : 333-376
                Affiliations
                [A1] 1Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
                [A2] 2Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
                [A3] 3Department of Internal Medicine, Mount Sinai Medical Center Miami Beach, FL, USA
                [A4] 4Wellness Quest, LLC, Grand Prairie, TX, USA
                [A5] 5Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
                Author notes
                [* ] Corresponding author: John E. Lewis University of Miami Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, 1120 NW 14 th Street, Suite #1482A (D28), Miami, FL 33136, USA Tel: +1 305-243-6227 Fax: +1 305-243-1619 E-mail: jelewis@ 123456miami.edu
                Article
                jctres.07.202103.004
                10.18053/jctres.07.202103.004
                8259612
                34239993
                5db57ac1-c9c8-40e0-aa15-f0e2147e57bf
                Copyright: © Whioce Publishing Pte. Ltd.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY-NC-ND 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 January 2021
                : 10 April 2021
                : 27 April 2021
                Categories
                Review Article

                immune function,immunomodulation,inflammation,nutrients,phytonutrients

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