-
1.
The Functional Medicine Approach to COVID-19: Virus-Specific Nutraceutical and Botanical Agents.
Evans, JM, Luby, R, Lukaczer, D, Rountree, R, Stone, PM, Guilliams, TG, Yanuck, S, Messier, H, Ramsdell, K, Hanaway, PJ
Integrative medicine (Encinitas, Calif.). 2020;19(Suppl 1):34-42
-
-
-
Free full text
Plain language summary
The practice of Functional Medicine, with respect to interventions, emphasizes the primacy of safety, validity, and effectiveness. Data for the effectiveness of interventions targeting the viral mechanisms of Covid-19 are nascent and rapidly emerging. The aim of this review was to assess the scientific plausibility of promising prevention approaches and therapeutic (nutraceutical and botanical) interventions and suggest clinical recommendations. A coronavirus such as SARS-CoV-2 can be deadly because of its ability to stimulate a part of the innate immune response called the inflammasome. This can cause uncontrolled release of pro-inflammatory cytokines, leading to cytokine storm and severe, sometimes irreversible, damage to respiratory epithelium. In order to prevent the activation of a particular inflammasome the following compounds are being recommended; quercetin, curcumin, epigallocatechin gallate, n-acetylcysteine, resveratrol, vitamin D, vitamin A, vitamin C, elderberry, melatonin, zinc and palmitoylethanolamide. Authors emphasise that the recommendations are meant to identify botanical and nutraceutical agents that may boost the immune system and not as a means of treatment.
Abstract
As the novel infection with SARS-CoV-2 emerges, objective assessment of the scientific plausibility of nutraceutical and botanical interventions for prevention and treatment is important. We evaluate twelve such interventions with mechanisms of action that modulate the immune system, impair viral replication, and/or have been demonstrated to reduce severity of illness. These are examples of interventions that, mechanistically, can help protect patients in the presence of the prevalent and infectious SARS-CoV-2 virus. While there are limited studies to validate these agents to specifically prevent COVID-19, they have been chosen based upon their level of evidence for effectiveness and safety profiles, in the context of other viral infections. These agents are to be used in a patient-specific manner in concert with lifestyle interventions known to strengthen immune response (see related article in this issue of IMCJ).
-
2.
COVID-19 and diabetes: The why, the what and the how.
Cuschieri, S, Grech, S
Journal of diabetes and its complications. 2020;34(9):107637
-
-
-
Free full text
-
Plain language summary
Early reports have shown that individuals with diabetes who contract Covid-19 have higher hospital admissions and mortality rates, classing them as a vulnerable group. This review paper aimed to explain why this group of people are vulnerable and what measures could be recommended. The paper outlined that individuals with diabetes have a compromised immune system due to uncontrolled blood sugar levels. In addition to this, individuals with diabetes and Covid-19 may have a higher risk of organ damage due to the effects of the body's immune response combined with the disordered biological processes associated with their pre-existing condition. Conversely, it was discussed that Covid-19 could exacerbate diabetes progression if the Covid-19 virus entered the cells of the pancreas, causing a blood sugar imbalance. As a result, the importance of optimal blood sugar control was outlined. Several medications were addressed and their benefits/disadvantages discussed. Amongst those reviewed were medications such as GLP-1 agonists, which may help with controlling blood sugar levels and may prevent Covid-19 entering the body's own cells, and metformin, which was initially developed as an anti-influenza drug. Finally the paper discussed diabetes specific precautions to avoid contracting Covid-19. Vitamin D supplementation, regular blood sugar checks, lifestyle measures such as exercise and dietary requirements and allowing individuals with diabetes to have large supplies of their medications to avoid leaving the house were discussed. It was concluded that during the Covid-19 pandemic, individuals with diabetes require particular care in order to avoid additional burden on healthcare systems. For those individuals with diabetes who haven’t contracted Covid-19, this paper could be used to recommend any extra precautions to take to avoid contracting this virus.
Abstract
BACKGROUND The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS A search using keywords "COVID-19" and "Diabetes" was performed using different sources, including PubMed and World Health Organization. RESULTS COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute β-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.
-
3.
Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?
Knezevic, J, Starchl, C, Tmava Berisha, A, Amrein, K
Nutrients. 2020;12(6)
-
-
-
Free full text
Plain language summary
Thyroid and gut disease often coexist together. This literature review highlights the strong interplay between gut, microbiota and thyroid disease. In autoimmune thyroid disease (AITD) gut bacteria imbalances, bacterial overgrowth, Coeliac's disease or non-coeliacs wheat sensitivity, increased gut permeability and resulting deficiency of thyroid nutrients are not uncommon. Inflammation and intestinal wall damage that lead to increased permeability are thought to be one of the driving factors for autoimmune activity. Allergens, certain drugs, impaired gut flora and nutrient deficiencies are some of the contributors to heightened intestinal permeability. Furthermore, the gut walls host deiodinase enzymes that convert thyroid hormone to its active form. The gut microbiota however influence thyroid function in their own rights. The bacteria are crucial for nutrient synthesis, absorption and availability, including those essential for thyroid health. Gut bacteria and their metabolites also play a significant role in the regulation, development and training of immune cells, relevant to AITD. After all, the gut also houses a large proportion of the immune system known as gut-associated lymphatic tissue (GALT). Besides, some bacteria species seem to be capable of balancing fluctuating thyroid hormone levels in the blood. The writings further elaborate on thyroid-essential nutrients and the gut such as iodine, iron, zinc, selenium and Vitamin D. And the impact of bariatric surgery on thyroid function and the presence of certain gut bacteria in thyroid cancers. In summary, the authors concluded that the thyroid-gut axis seems to exhibit a strong connection. Limited evidence from human studies showed promising results of probiotics and synbiotics on thyroid function and targeting the microbiota as a novel strategies for the management of thyroid disease is encouraged to be explored further. This article may be of interest to those looking for an informative summary on the many ways in which the gut influences thyroid function in health and disease.
Abstract
A healthy gut microbiota not only has beneficial effects on the activity of the immune system, but also on thyroid function. Thyroid and intestinal diseases prevalently coexist-Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the most common autoimmune thyroid diseases (AITD) and often co-occur with Celiac Disease (CD) and Non-celiac wheat sensitivity (NCWS). This can be explained by the damaged intestinal barrier and the following increase of intestinal permeability, allowing antigens to pass more easily and activate the immune system or cross-react with extraintestinal tissues, respectively. Dysbiosis has not only been found in AITDs, but has also been reported in thyroid carcinoma, in which an increased number of carcinogenic and inflammatory bacterial strains were observed. Additionally, the composition of the gut microbiota has an influence on the availability of essential micronutrients for the thyroid gland. Iodine, iron, and copper are crucial for thyroid hormone synthesis, selenium and zinc are needed for converting T4 to T3, and vitamin D assists in regulating the immune response. Those micronutrients are often found to be deficient in AITDs, resulting in malfunctioning of the thyroid. Bariatric surgery can lead to an inadequate absorption of these nutrients and further implicates changes in thyroid stimulating hormone (TSH) and T3 levels. Supplementation of probiotics showed beneficial effects on thyroid hormones and thyroid function in general. A literature research was performed to examine the interplay between gut microbiota and thyroid disorders that should be considered when treating patients suffering from thyroid diseases. Multifactorial therapeutic and preventive management strategies could be established and more specifically adjusted to patients, depending on their gut bacteria composition. Future well-powered human studies are warranted to evaluate the impact of alterations in gut microbiota on thyroid function and diseases.
-
4.
The Effect of a Multivitamin and Mineral Supplement on Immune Function in Healthy Older Adults: A Double-Blind, Randomized, Controlled Trial.
Fantacone, ML, Lowry, MB, Uesugi, SL, Michels, AJ, Choi, J, Leonard, SW, Gombart, SK, Gombart, JS, Bobe, G, Gombart, AF
Nutrients. 2020;12(8)
-
-
-
Free full text
Plain language summary
Vitamins and minerals are essential for a healthy immune system. The prevalence of vitamin and mineral deficiencies increases with age, and this may contribute to age-related decline of the immune system. The aim of this study was to investigate whether a daily multivitamin and mineral (MVM) supplement could improve the immune function of older people. 42 healthy adults aged between 55 and 75 took part in this single-centre, two-armed, parallel, randomised, double-blinded study. Half of the group was given a MVM supplement called Redoxon Vita Immune (VI) containing the vitamins A, D, E, C, B6, B12 and folate plus iron, copper, zinc and selenium daily for 12 weeks, whilst the other half was given placebo tablets for 12 weeks. Participants were instructed to avoid certain foods high in vitamins and minerals such as oily fish, red meat, liver, and citrus fruits during the study period. Blood and saliva samples were taken from all participants at the beginning and end of the study period, to measure vitamin and mineral status and markers of immune function. Participants also kept a diary to record any illnesses or symptoms. At the end of the study, participants given the MVM supplement had increased their blood levels of vitamin C by 126% and zinc by 43%. There was no significant change in blood levels of vitamin D. There was no significant difference in the potential of blood to kill the introduced bacteria Staphylococcus aureus, or in neutrophil activity, nor were there any significant changes in blood levels of cytokines and chemokines. Participants taking the supplement did however report a shorter length, and lower severity of illnesses compared to those taking the placebo. The authors concluded that their findings support further research to test whether MVM supplementation can improve immune outcomes in older adults.
Abstract
Older adults are at increased risk for vitamin and mineral deficiencies that contribute to age-related immune system decline. Several lines of evidence suggest that taking a multi-vitamin and mineral supplement (MVM) could improve immune function in individuals 55 and older. To test this hypothesis, we provided healthy older adults with either an MVM supplement formulated to improve immune function (Redoxon® VI, Singapore) or an identical, inactive placebo control to take daily for 12 weeks. Prior to and after treatment, we measured (1) their blood mineral and vitamin status (i.e., vitamin C, zinc and vitamin D); (2) immune function (i.e., whole blood bacterial killing activity, neutrophil phagocytic activity, and reactive oxygen species production); (3) immune status (salivary IgA and plasma cytokine/chemokine levels); and (4) self-reported health status. MVM supplementation improved vitamin C and zinc status in blood and self-reported health-status without altering measures of immune function or status or vitamin D levels, suggesting that healthy older adults may benefit from MVM supplementation. Further development of functional assays and larger study populations should improve detection of specific changes in immune function after supplementation in healthy older adults. Clinical Trials Registration: ClinicalTrials.gov #NCT02876315.
-
5.
'The long tail of Covid-19' - The detection of a prolonged inflammatory response after a SARS-CoV-2 infection in asymptomatic and mildly affected patients.
Doykov, I, Hällqvist, J, Gilmour, KC, Grandjean, L, Mills, K, Heywood, WE
F1000Research. 2020;9:1349
-
-
-
Free full text
Plain language summary
‘Long COVID’ or the persistence of symptoms after SARS-CoV-2 infection, such as fatigue, is becoming increasingly common. As the emergence of the virus is still relatively recent in research terms, little is known about the long-term impact of the viruses infection. This study sought to generate further insights into the management and diagnostic of long COVID, by assessing a range of inflammatory markers from blood serum samples. Examined were 10 samples of health care workers with previous asymptomatic or moderate SARS-CoV-2 infections, compared to 10 samples of SARS-CoV-2 naive health care workers. The serum was analyzed by mass spectrometry using a customized panel of the 96 immune response associated proteins. Despite being mild to moderate cases, the results showed that even 40-60 days after infection, significant disturbance in the immune systems inflammatory response could be observed. Particularly markers that reflect anti-inflammatory pathways and mitochondrial stress. The study highlighted six of the most noteworthy proteins and included a brief description of their role. The authors suggest that analysing proteins by using targeted proteomic technology, could serve as a cost-effective strategy to further investigate the changes in inflammatory responses post SARS-CoV-2 infection. Which could help to aid the identification of potential treatment targets in the future. Relevant findings from this small study for clinical practice are that even mild to moderate SARS-CoV-2 infection can alter the inflammatory responses for months afterwards.
Abstract
'Long Covid', or medical complications associated with post SARS-CoV-2 infection, is a significant post-viral complication that is being more and more commonly reported in patients. Therefore, there is an increasing need to understand the disease mechanisms, identify drug targets and inflammatory processes associated with a SARS-CoV-2 infection. To address this need, we created a targeted mass spectrometry based multiplexed panel of 96 immune response associated proteins. We applied the multiplex assay to a cohort of serum samples from asymptomatic and moderately affected patients. All patients had tested positive for a SARS-CoV-2 infection by PCR and were determined to be subsequently positive for antibodies. Even 40-60 days post-viral infection, we observed a significant remaining inflammatory response in all patients. Proteins that were still affected were associated with the anti-inflammatory response and mitochondrial stress. This indicates that biochemical and inflammatory pathways within the body can remain perturbed long after SARS-CoV-2 infections have subsided even in asymptomatic and moderately affected patients.
-
6.
Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections.
Calder, PC, Carr, AC, Gombart, AF, Eggersdorfer, M
Nutrients. 2020;12(4)
-
-
-
Free full text
Plain language summary
Acute respiratory tract infections are a major cause of morbidity and mortality across the globe with seasonal influenza epidemics and outbreaks of viruses, such as Covid-19. The authors support public hygiene practices and the development of vaccinations however call for further strategies in order to reduce the impact that these infections have on societies. The role nutrition plays in supporting the immune system is well established. This review article and opinion piece presents the evidence for Vitamins A, B6, B12, C, D, E and folate; trace elements including zinc, selenium, magnesium and copper; and omega-3 fatty acids in supporting the immune system. The authors call for the consumption of a well-balanced diet, with additional supplementation of key immune supportive nutrients. Well referenced and with a helpful table of the rationale and recommended nutrient intake levels, Nutrition Practitioners will find this article useful when working to support client immune health.
Abstract
Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, were responsible for approximately 2.38 million deaths worldwide in 2016. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: (1) supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; (2) supplementation above the Recommended Dietary Allowance (RDA), but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and (3) public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.
-
7.
Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.
Leung, TYM, Chan, AYL, Chan, EW, Chan, VKY, Chui, CSL, Cowling, BJ, Gao, L, Ge, MQ, Hung, IFN, Ip, MSM, et al
Emerging microbes & infections. 2020;9(1):2190-2199
-
-
-
Free full text
Plain language summary
The Coronavirus pandemic (Covid-19) has infected millions of people worldwide and there is evidence that it affects many systems in the human body. This rapid review summarises the current evidence on short-term negative health outcomes of Covid-19. It also assesses the risk of potential long-term negative effects by looking at data from the other coronaviruses; Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The burden for caring for Covid-19 survivors is likely to be huge and so policy makers need suitable data to put the appropriate care strategies in place. The review is divided into sections as per body system affected: Immune, respiratory, cardiovascular, gastrointestinal, hepatic and renal, neurological, dermatological, mental health, pregnancy and prenatal exposure. The evidence (short-term and long-term) is then reviewed by experts in those fields. Further large-scale studies are needed to monitor the adverse effects and to measure the long-term health consequences.
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.
-
8.
Recent Advances in Psoriasis Research; the Clue to Mysterious Relation to Gut Microbiome.
Komine, M
International journal of molecular sciences. 2020;21(7)
-
-
-
Free full text
Plain language summary
Psoriasis is a chronic inflammatory disease where the skin forms bumpy red patches covered with white scales. There is no cure, but medications have focused on supressing the immune response. There is a link between the gut microbiome and psoriasis but it is poorly understood. This review includes the current understanding of how psoriasis develops and discusses the recent findings to support further research in this area. The composition of the gut microbiome affects inflammation in the whole body. This inflammation is associated with cardiovascular disease, diabetes mellitus and other inflammatory disorders. Recent studies have linked cardiovascular disease, insulin resistance, and metabolic syndrome to an imbalance in the gut microbiome. Psoriasis is often found alongside these conditions with similar abnormalities in gut bacteria. An imbalance in gut microbiome could cause certain people to develop psoriasis. The role of the gut microbiome needs to be further clarified but mounting evidence for this gut/skin link means that other therapeutic options may be available for treatment in the future.
Abstract
Psoriasis is a chronic inflammatory cutaneous disease, characterized by activated plasmacytoid dendritic cells, myeloid dendritic cells, Th17 cells, and hyperproliferating keratinocytes. Recent studies revealed skin-resident cells have pivotal roles in developing psoriatic skin lesions. The balance in effector T cells and regulatory T cells is disturbed, leading Foxp3-positive regulatory T cells to produce proinflammatory IL-17. Not only acquired but also innate immunity is important in psoriasis pathogenesis, especially in triggering the disease. Group 3 innate lymphoid cell are considered one of IL-17-producing cells in psoriasis. Short chain fatty acids produced by gut microbiota stabilize expression of Foxp3 in regulatory T cells, thereby stabilizing their function. The composition of gut microbiota influences the systemic inflammatory status, and associations been shown with diabetes mellitus, cardiovascular diseases, psychomotor diseases, and other systemic inflammatory disorders. Psoriasis has been shown to frequently comorbid with diabetes mellitus, cardiovascular diseases, psychomotor disease and obesity, and recent report suggested the similar abnormality in gut microbiota as the above comorbid diseases. However, the precise mechanism and relation between psoriasis pathogenesis and gut microbiota needs further investigation. This review introduces the recent advances in psoriasis research and tries to provide clues to solve the mysterious relation of psoriasis and gut microbiota.
-
9.
Melatonin: Roles in influenza, Covid-19, and other viral infections.
Anderson, G, Reiter, RJ
Reviews in medical virology. 2020;30(3):e2109
-
-
-
Free full text
-
Plain language summary
Viruses like influenza and coronaviruses change quickly, making it challenging to develop effective treatments and vaccines in a short time frame. Consequently, the use of generic substances that limit viral effects are of high interest. In this paper, the authors summarize a range of mechanisms in which melatonin can alter the impact of virus infections and infection-associated inflammatory overdrive aka cytokine storm. Melatonin, the sleep hormone, is well known for its potent antioxidant and anti-inflammatory action. It seems highly likely that melatonin can modulate the cellular function of all cells, mostly via mitochondrial function. This is particularly relevant in immune cells. For example, the daytime variance in immune function seems to be closely linked with mitochondrial activity and energy production. Other relevant mechanisms described are the antiviral role of melatonin-induced sirtuins - proteins that regulate cellular health-, the impact of viruses on cell coordinating microRNA, the role of the gut microbiome and gut permeability, as well as sympathetic nervous system activation and the protective effects of parasympathetic activation. Also considered are pre-existing health conditions and conditions that are linked with a decline in melatonin along with ageing, all being groups in which severity of viral infections is felt. This paper may be of interest to those who like to explore in more depth the mechanisms behind melatonin and its ability to influence viral disease progression.
Abstract
There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function. We review the melatonergic pathway role in viral infections, emphasizing influenza and covid-19 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial "cytokine storm", as well as the regulation of other immune cells. Melatonin induces the circadian gene, Bmal1, which disinhibits the pyruvate dehydrogenase complex (PDC), countering viral inhibition of Bmal1/PDC. PDC drives mitochondrial conversion of pyruvate to acetyl-coenzyme A (acetyl-CoA), thereby increasing the tricarboxylic acid cycle, oxidative phosphorylation, and ATP production. Pineal melatonin suppression attenuates this, preventing the circadian "resetting" of mitochondrial metabolism. This is especially relevant in immune cells, where shifting metabolism from glycolytic to oxidative phosphorylation, switches cells from reactive to quiescent phenotypes. Acetyl-CoA is a necessary cosubstrate for arylalkylamine N-acetyltransferase, providing an acetyl group to serotonin, and thereby initiating the melatonergic pathway. Consequently, pineal melatonin regulates mitochondrial melatonin and immune cell phenotype. Virus- and cytokine-storm-driven control of the pineal and mitochondrial melatonergic pathway therefore regulates immune responses. Virus-and cytokine storm-driven changes also increase gut permeability and dysbiosis, thereby suppressing levels of the short-chain fatty acid, butyrate, and increasing circulating lipopolysaccharide (LPS). The alterations in butyrate and LPS can promote viral replication and host symptom severity via impacts on the melatonergic pathway. Focussing on immune regulators has treatment implications for covid-19 and other viral infections.
-
10.
Can Vitamin D and L-Cysteine Co-Supplementation Reduce 25(OH)-Vitamin D Deficiency and the Mortality Associated with COVID-19 in African Americans?
Jain, SK, Parsanathan, R
Journal of the American College of Nutrition. 2020;39(8):694-699
-
-
-
Free full text
-
Plain language summary
African Americans are more susceptible to vitamin D deficiency. In addition they have lower amounts of cellular glutathione (GSH), which is an antioxidant produced in the body from L-cysteine, capable of affecting genes involved in vitamin D production. Clinical trials have indicated a relationship between vitamin D deficiency and poorer outcomes in patients with COVID-19. This review paper looked at data in humans, animal models and at the cellular level and proposed that African Americans are susceptible to vitamin D deficiency due to increased skin pigmentation affecting its production. Reduced GSH was attributed to decreased dietary intake of L-cysteine, and lower levels of biological compounds, which are involved in the production of GSH. Research surrounding vitamin D’s role in immunity and lowering viral infection risk was reviewed and several routes were proposed, such as increasing anti-microbial action, decreasing inflammation, increasing anti-oxidants and blocking viruses entering cells. It was concluded that randomised control trials on vitamin D supplementation have been underwhelming. This disconnect with trials showing a relationship between low vitamin D levels and poor clinical outcomes is due to the fact that vitamin D was tested in isolation. More randomised control trials are needed to investigate co-supplementation with L-cysteine on outcomes of COVID-19 infection in African Americans. Clinicians could use this review to understand the relationship between vitamin D and L-cysteine and, in lieu of any randomised control trials, as a potential justification for co- supplementation of Vitamin D and L-cysteine in patients with vitamin D deficiency and COVID-19.
Abstract
Early reports indicate an association between the severity of the COVID-19 infection and the widespread 25-hydroxy vitamin D deficiency known to exist in populations around the world. Vitamin D deficiency is extremely common among African American (AA) communities, where the COVID-19 infection rate is three-fold higher, and the mortality rate nearly six-fold higher, compared with rates in predominantly white communities. COVID-19 infection primarily affects the lungs and airways. Previous reports have linked 25-hydroxy vitamin D deficiency with subclinical interstitial lung disease. AA are at risk for lower cellular glutathione (GSH) levels, and GSH deficiency epigenetically impairs VD biosynthesis pathway genes. Compared with vitamin D alone, co-supplementation of vitamin D and L-cysteine (a GSH precursor) showed a better efficacy in improving levels of GSH and VD-regulatory genes at the cellular/tissue level, increasing 25(OH) vitamin D levels, and reducing inflammation biomarkers in the blood in mice studies. We propose that randomized clinical trials are needed to examine the potential of co-supplementation with anti-inflammatory antioxidants, vitamin D and L-cysteine in correcting the 25(OH)VD deficiency and preventing the 'cytokine storm,' one of the most severe consequences of infection with COVID-19, thereby preventing the adverse clinical effects of COVID-19 infection in the vulnerable AA population.