- The majority of randomized controlled trials have shown vitamin D does not decrease the risk of COVID-19 infection. However, observational studies have shown a correlation between the two. Researchers believe the disparity may be based in the difficulty of coordinating these studies, as participants may began with varying vitamin D levels, and the dosages between studies may not be consistent. 
- Studies have found that individuals with chronic diseases are likely to also have low vitamin D levels. It is unclear if risk of infection correlates with chronic disease and not vitamin D or a combination of the two. 

Clinical and Epidemiological Findings Regarding Vitamin D and COVID-19 

- 25-hydroxyvitamin D, which measures vitamin D levels in the body, is lowest during the winter. Notably, this is when the COVID-19 outbreak began. Individuals should monitor vitamin D through the winter months as a precaution against a deficiency. 
- Individuals hoping to protect against COVID-19 should consider taking 10,000 IU/d of vitamin D3 for a few weeks before lowering the dose to 5000 IU/d.
- For those already infected with COVID-19, it is hypothesized taking the higher dose may still provide some benefit. 

Proposed Vitamin D Dosage to Mitigate COVID-19

- Studies have found doses of up to 10,000 IU/d vitamin D3 are entirely safe and do not cause adverse effects. Higher doses, up to 600,000 IU/d, were found to protect against other diseases, including asthma, though hypercalcemia was reported among participants. These high doses are not recommended. 
- While several studies have proven the safety of vitamin D, many countries do not have guidelines for supplying individuals with vitamin D supplements, and many remain skeptical of the health benefits. 
- Individuals may choose to increase their vitamin D levels by instead consuming flour and dairy products, though this is not as effective as a supplement. 
- Currently, the exact link between vitamin D and COVID-19 remains unclear, and more research is needed. 

Uncertainty in Using Vitamin D to Mitigate COVID-19

Influenza, HIV, and hepatitis C have been associated with Vitamin D deficiency as a predisposition to these diseases. 
Lower Vitamin D levels in calves has been reported to increase risk for bovine coronavirus.

Vitamin D deficiency associated with viral diseases

Vitamin D is a nutrient that is both endogenously synthesized in the skin and consumed dietarily.  Its biologically active form [1,25-(OH)2D] is a known negative regulator of the Renin-Angiotensin System (RAS).  1,25-(OH)2D has been shown to increase ACE2 expression and suppress the inflammatory outcomes caused by angiotensin II (Ang II).  Additionally, vitamin D can modulate the immune system by inhibiting B-cell and T-cell proliferation as well as inducing T-regulatory cells, which suppress pro-inflammatory cytokines and increase anti-inflammatory cytokines.  These processes may make vitamin D a useful molecule in treating or preventing a SARS-CoV-2 infection.

Michigan State University

Kenyon College

- "Western diets" and saturated fatty acids
- High fiber and balanced diets
- Malnutrition 
- Overnutrition
- Noncommunicable Diseases 
- Vitamin D
- Nutrition Therapy in Critically Ill Patients With Coronavirus Disease 2019
- Eucaloric Ketogenic Diet (EKD)
- Nutritional status of patients with coronavirus disease 2019 (COVID-19)
- Easy-to-prescribe nutrition support in the intensive care in the era of COVID-19
- Anti-inflammatory foods 
- Nutrigenomics
- Epigenetics
- Polyphenols
- Gastrointestinal Manifestations of COVID-19
- Vitamin C
- Maternal and child health

Focuses of Effects of human nutrition in fighting COVID-19

Vitamin D is a nutrient that is synthesized endogenously from 7-dehydrocholesterol by the skin after UV-B exposure from sunlight and is also found in some foods.  It is processed in the liver by the enzyme 25-hydroxylase to form 25-hydroxyvitamin D [25(OH)D].  It is then further processed by the enzyme 1-ɑ-hydroxylase (CYP27B1) to form the biologically active molecule 1,25-dihydroxyvitamin D [1,25(OH)2D].  This molecule can then go on to interact with vitamin D receptors in a variety of tissues which are involved in physiological processes such as the endocrine regulation of minerals and some cell signaling mechanisms related to immune responses.  

Vitamin D

Regulators of the Renin-Angiotensin System (RAS)

Vitamin D is both a paracrine (cell-to-cell) and autocrine (self) signaling molecule.  All cells in the immune system either express vitamin D receptors or have the ability to.  Additionally, they are all sensitive to the activity of its biologically active counterpart 1,25(OH)2D.  Vitamin D deficiency may weaken the body's control of immune responses and impair other physiological processes that involve vitamin D, including regulation of the renin-angiotensin system (RAS).  Therefore, these phenomena may make the body more susceptible to a SARS-CoV-2 infection.  

Vitamin D Deficiency May Exacerbate SARS-CoV-2 Infections

Grant, W. B., Lahore, H., McDonnell, S. L., Baggerly, C. A., French, C. B., Aliano, J. L., & Bhattoa, H. P. (2020). Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients, 12(4), 988. doi:10.3390/nu12040988
https://www.mdpi.com/2072-6643/12/4/988

Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

Zwart, S. R., & Smith, S. M. (2020). Vitamin D and COVID-19: Lessons from Spaceflight Analogs. The Journal of Nutrition.
https://academic.oup.com/jn/article/doi/10.1093/jn/nxaa233/5876210
doi: 10.1093/jn/nxaa233

Vitamin D and COVID-19: Lessons from Spaceflight Analogs

A Western Diet is high in saturated fatty acids, refined carbohydrates, and sugars. It is also marked by low consumption of fiber, unsaturated fats, and antioxidants.

Western Diets

Proper nutrition is essential for the body to fight off viral infections. Lack of proper nutrition can not only decrease the immune system's ability to fend off infection, but also increase the likelihood of other comorbidities that increase the fatality of COVID-19.

The effects of malnutrition on fighting COVID-19

Noncommunicable diseases, also known as chronic diseases, are noninfectious and may be caused by an individual's lifestyle, genetics, or environment. There is a direct link between noncommunicable diseases and the severity of viral infections. 

As such, conditions like high blood pressure and diabetes are thought to exacerbate the severity of COVID-19. Researchers propose the best way to combat COVID-19 for individuals with noncommunicable diseases is based in lifestyle changes, with a focus mostly on diet. See: 

- The Mediterranean Diet 
- Vitamins C, D, and E 
- Zinc, Copper, and Fiber 

Noncommunicable Diseases

As therapeutic interventions remain largely experimental, supportive care in the form of nutrition management is integral for critically ill patients.

Nutrition Therapy in Critically Ill Patients With CoronavirusDisease 2019

High fiber and balanced diets are rich in whole grains, cereals, fruits, vegetables and legumes . 

High fiber and balanced diets 

Individual diet plays a significant role in affecting immune response and COVID-19 susceptibility. On the molecular level, certain intake of nutrients can contribute to the activation of certain helper T-cells, B-cells, etc. as well as secretion of signaling molecules like transcription factors that can modulate gene expression. For instance, high consumption of red meat, high glycemic index (GI) food, and high fat often lead to accumulation of visceral fat that causes hormonal imbalances in cytokines secretions. One common effect is chronic expression of pro-inflammatory cytokines like TNFα, IL-1β, and IL-6. Long-term expression of these cytokines triggers increase of Leptin, a downstream cytokine that serves as a positive feedback loop in further enhancing the expression of TNFα, IL-1β, and IL-6. Expression of these cytokines has found to be involved with decreased T-cell population, which explains why this kind of diet increased susceptibility and allergic reactions as well as poor antibody response, particularly in obese populations.
On the microbial level, specific nutrients consumption also play a significant role in shaping the gut microbiome, which can directly influence immune response. Deficiencies in calories, protein, minerals, and vitamins are commonly correlated with suppressed immune surveillance and susceptibility to infection. In the intestinal lumen, various antimicrobial peptides were secreted to impede growth of certain microbe over another. It is evident that to some extent, the gut microbiome has direct interaction with modulating immune homeostasis that finely control pro and anti-inflammatory responses. Microbes play significant roles in fingerprinting microorganism-associated molecular patterns (MAMPs) and pathogen-associated molecular patterns (PAMPs). A typically healthy gut microbiome will contain some of the common bacterial taxonomies like lactobacillus, bacteriodes, and bifidobacteria that secrete certain metabolites and other immune-modulatory signals that often contain short chain fatty acids (SCFA) like acetate and butyrate. These molecules can bind to certain receptors like toll-like receptors of innate cells that can have effect on their metabolism and activity. 


Effects of Nutrition and Gut Microbiome on Immune Response to COVID-19

Using Vitamin D to Mitigate COVID-19

An imbalanced nutritional status resulting from excessive intake of nutrients generated by an energy imbalance between food consumption and energy expenditure leading to disorders such as obesity.

Overnutrition

Compounds in plants that can have healing and therapeutic properties for treating illnesses or injuries. 


Phytomedicines 

The eucaloric ketogenic diet is a diet consisting of mainly fat and minimal amounts of carbohydrates. It provides the body with sufficient calories while it stabilizes blood glucose levels and reduces oxidative stress.

Eucaloric Ketogenic Diet (EKD)

Among 50 (mean age 52.2, SD 20.7) hospitalized patients with COVID-19, 76% were deficient in vitamin D and 42% in selenium. Among the nutrients zinc, B1, B6, B12, folate, vitamin D, selenium, all the 12 patients with severe respiratory distress and advanced stage of the disease had a deficiency in more than one nutrient .

Nutritional status of patients with coronavirus disease 2019 (COVID-19)

Due to the large influx of Covid-19 ICU patients, a new protocol has been developed to provide easier and simplified nutritional distribution. At the end of the pandemic wave, the protocol was evaluated in the form of questionnaires and surveys. 122 physicians on the ICU medical team received the protocol and a great majority of the medical team as well as the participants assessed it as a useful tool for nutritional therapy.

Easy-to-prescribe nutrition support in the intensive care in the era of COVID-19

Foods used to treat chronic illnesses have shown to improve the health of patients who have COVID-19 as well. Some examples of these foods are:

-Vegetables: Broccoli, kale, Brussels sprouts, cabbage, cauliflower, etc.


-Fruit: Especially deeply colored berries like grapes and cherries


-High-fat fruits: Avocados and olives


-Healthy fats: Olive oil and coconut oil


-Fatty fish: Salmon, sardines, herring, mackerel, and anchovies


-Nuts: Almonds and other nuts


-Peppers: Bell peppers and chili peppers


-Chocolate: Dark chocolate


-Spices: Turmeric, fenugreek, cinnamon, etc.


-Tea: Green tea


-Red wine: Up to 5 ounces (140 ml) of red wine per day for women and 10 ounces (280 ml) per day for men

Anti-inflammatory Foods

SUMMARY OF CURRENT INFO
- Research for ACE1
- Research for AGTR1
- Research for ACE2
- Research for TMPRSS2 and ESR2
- Nutritional strategies

ARTICLES
- Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework

Nutrigenomics

ARTICLES RESEARCHED
- Can Vitamins, as Epigenetic Modifiers, Enhance Immunity in COVID-19 Patients with Non-communicable Disease?
- Epigenetic Diet to Modulate Immune Response against SARS-CoV-2
- The epigenetic implication in coronavirus infection and therapy

Epigenetics

Polyphenols is from plant based food and a potential use for against COVID-19. 

Polyphenols

Even though COVID-19 is primarily viewed as a reparatory illness, it has also been found to affect the gastrointestinal system. Therefore, there is an increasing need for a focus on gastroenterology to establish proper nutrition therapies. To develop these nutrition therapies, a better understanding of preexisting gastrointestinal diseases is vital, as well as consideration of the challenges and obstacles of nutrition therapy.

Gastrointestinal Manifestations of COVID-19: Impact on Nutrition Practices

Vitamin C, ascorbic acid, is a required nutrient for humans that humans are unable to endogenously synthesize.  Therefore, humans are dependent of food and other external sources for sources of vitamin C.
A deficiency of vitamin C has been found to be linked with respiratory infections, and current evidence suggests that 2-8 g/day of oral vitamin C may reduce the incidence and duration of these respiratory infections, including COVID-19.  

Using Vitamin C to mitigate Covid-19

- COVID-19 pandemic and mitigation strategies: implications for maternal and child health and nutrition

Nutrition and Maternal and Child Health in COVID-19

Clinically, vitamin D deficiency is defined as having circulating 25(OH)D concentrations < 20 ng/mL.  Approximately one billion people worldwide fit into this category.  Vitamin D deficiency is associated with geographic location, as people who live further from the equator have less sunlight exposure.  Darker complected skin has been shown to reduce the ability of UV-B radiation to synthesize vitamin D in the skin.  Additionally, advanced age decreases the ability of skin to synthesize the vitamin.  

Vitamin D Deficiency

Vitamin D insufficiency affects almost 50% of the population worldwide. An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency (VDD). VDD results in abnormalities in calcium, phosphorus, and bone metabolism. the major cause of VDD is inadequate exposure to sunlight. VDD causes a decrease in the absorption of dietary calcium and phosphorus, resulting in an increase in PTH levels.

Vitamin D Insufficiency

Inhibitors of the Renin-Angiotensin-Aldosterone pathway (ie. ACE inhibitors, angiotensin-receptor blockers) are commonly used to treat hypertension. Previous animal studies, which have shown that these inhibitors can increase the level of ACE2 expression in one's body, coupled with the cardiovascular comorbidities, lead to speculation amongst clinicians and researchers that these widely-used drugs may be harmful for patients with COVID-19. Current studies (June 2020) have shown no evidence of harm with continued use of RAAS inhibitors in COVID-19 patients. 

- database study involving 8910 patients from 11 countries
- case control study in the Lombardy region of Italy
- study based on data from the electronic health records in the New York University Langone Health system


Inhibitors of the Renin–Angiotensin–Aldosterone System (RAAS) and COVID-19

University of Chicago Medicine found an association between vitamin D deficiency and the likelihood of becoming infected with the coronavirus.

Patients whose vitamin D levels were tested last year to be deficient (< 20ng/ml and untreated were twice as likely to test positive for the COVID-19 compared to patients who had sufficient levels of the vitamin. 

https://www.uchicagomedicine.org/forefront/coronavirus-disease-covid-19/vitamin-d-deficiency-may-raise-risk-of-getting-covid19

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