A new paper published in August in the American Journal of Epidemiology sheds some light on whether omega-3s can play a role in protecting the lungs, which is particularly important these days given the coronavirus pandemic.
The new study looked at a condition called interstitial lung disease (ILD), which is a constellation of disorders that cause, among other things, progressive scarring to the lungs. This scarring affects the ability to breathe and get enough oxygen into the bloodstream.
The omega-3 DHA has been shown in experimental models to reduce ILD but human studies are lacking. For this paper, OmegaQuant’s Dr. Bill Harris and his colleagues examined cross-sectional associations with lung abnormalities in 3 studies — Multi-Ethnic Study of Atherosclerosis (MESA), Framingham Heart Study (FHS), and Age Gene/Environment Susceptibility (AGES) Study — for a total study population of more than 10,000 subjects. They examined associations of circulating levels of omega-3 DHA, and other fatty acids, with hospitalization and death due to ILD over a 12-year period.
Omega-3 levels were analyzed from fasting blood samples and extracted from plasma phospholipids (MESA and AGES) or red blood cell membranes (FHS).
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What Dr. Harris and his colleagues found was that DHA levels were associated with a lower risk of hospitalizations due to ILD, in addition to a lower rate of death due to ILD. Higher DHA was also associated with less interstitial lung abnormalities on CT.
“I think the take-home message of this study is that the severity of an inflammatory disease – this time in the lung – is inversely related to blood omega-3 levels. That is, after adjusting statistically for the other factors that could make one susceptible to interstitial lung disease, a low DHA level was still associated with increased risk for having ILD by lung CT scanning,” Dr. Harris explained.
“More importantly, a low DHA level was associated with having a greater risk of being hospitalized for ILD and for dying from ILD-related lung disorders. This research suggests that having higher circulating omega-3 levels offer significant protection in this context, which is particularly timely given the COVID-19 pandemic,” Dr. Harris added.
The Connection Between Omega-3s & Asthma
A study published late last year in the Journal Nutrients correlated a higher Omega-3 Index with better asthma control and medication use.
While inhaled corticosteroids (ICS) are considered standard treatment for many asthmatics, researchers say dietary patterns are also being investigated for their potential preventative or therapeutic role.
More specifically, it has been suggested that a Western dietary pattern, high in energy, saturated fats, sugars and salt, may increase the prevalence and severity of asthma, independent of socioeconomic and lifestyle factors, according to researchers. Meanwhile, a Mediterranean dietary pattern, which is nutrient dense and high in fish, fruit and vegetables, could be protective, reducing the incidence and the severity of asthma symptoms.
One such way researchers believe the Mediterranean diet might be effective in reducing asthma symptoms is due to the high intake of omega-3s, which come from fatty fish like salmon, herring and sardines.
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Research has shown that omega-3s have established anti-inflammatory effects, thus having potential as an adjunct therapy in asthma. The purpose of this study was to compare the Omega-3 Index in adults with (n = 255) and without (n = 137) asthma to determine the relationship between blood levels of omega-3s and clinical asthma outcomes.
Researchers collected blood samples and measured lung function in study subjects. Blood was measured using the Omega-3 Index, while lung function was assessed via the Juniper Asthma Control Questionnaire (ACQ).
A higher Omega-3 Index was observed in subjects with controlled or partially controlled asthma compared to subjects with uncontrolled asthma. Subjects with a high Omega-3 Index (8% or higher) had a lower maintenance dose of ICS compared to those with a low Omega-3 Index.
Researchers in this study concluded that a higher Omega-3 Index is associated with better asthma control and with lower ICS dose, suggesting that having a higher level of omega-3s in the blood may play a role in asthma management. This is the first study, to the best of these researchers’ knowledge, reporting that a lower Omega-3 Index was associated with poorer asthma control in adults with asthma.
“Considering the high medication burden and reduced quality of life in people with asthma, our study suggests that higher levels of n-3 PUFA could be utilized as an adjunct therapy in the treatment of asthma,” the researchers commented. “Our findings suggest that achieving an Omega-3 Index of 8% or higher could be a beneficial target for people with asthma in order to reduce maintenance ICS dose.”
Can Omega-3s Help Weather the (Cytokine) Storm?
Another recent paper looked at the potential beneficial effect of omega-3 EPA and DHA on a phenomenon called a “cytokine storm.” In the June issue of Frontiers in Physiology, researchers evaluated the impact of these fatty acids on a cytokine storm, because a subgroup of patient death in the current COVID-19 pandemic has been attributed to this issue.
A “cytokine storm,” which is also called cytokine release syndrome or macrophage overactivation syndrome, happens when the body decides to attack itself rather than the virus. WebMD calls it as a “deranged” immune response.
“To date, the molecular events that precipitate a ‘cytokine storm’ or the applicable therapeutic strategies to prevent and manage this process is not elucidated because of the complex nature of this problem,” researchers say in their paper.
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“However, recent articles suggest that specific nutrients such as vitamin B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper may play a key role in the management of cytokine storm. Among these micronutrients LC-PUFAs (long chain polyunsaturated fatty acids) such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are noteworthy because of their direct influence in the immunological response to viral infections,” they added.
In their conclusion, the researchers said that based on the available data, the supplementation of EPA and DHA in COVID-19 patients appears to have potential beneficial effect in managing the “cytokine storm.”
“Therefore, the use of EPA and DHA supplementation should be considered as both a supportive therapy and a prevention strategy,” they said.
Omega-3s: Anti-Inflammatory Weapons for the Lungs?
Inflammation is only the first step in a highly complex, overall immune response to viral infections. In the context of COVID-19, there are a lot of conversations about “flattening the curve”, and that’s in a sense what EPA and DHA do within the body as it responds to infections. In other words, the infection does not cause an over-stimulation of the inflammatory response — it allows for what some call a “Goldilocks” response: not too much and not too little, but just right.
The mechanistic data clearly shows that omega-3s in cell membranes play an important role in taming the more toxic aspects of the immune response.
As the immune system can use toxic measures to destroy unwanted organisms (the innate piece), this has to be a targeted response (the adaptive piece), and there must be a healing from the collateral damage done by this powerful response. That healing is an active process itself called “resolution.” The resolution of the acute inflammatory response is mediated by metabolites of omega-3 fatty acids called “specialized pro-resolving mediators” (SPMs).
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The discovery of SPMs has been an exciting area of research lead by Dr. Charles Serhan over the last 20 years. SPMs are released over the hours and days following an inflammatory response, and they play an essential role in the healing process.
When there are lower levels of omega-3s in the body, there is less starting material for SPMs to be made from, and thus, a less effective healing process and lingering inflammation and damage.
A 2018 study by Norris and Skulas-Ray found that people taking a high dose of EPA+DHA (900-3400 mg/d) and then tested with an inflammatory challenge produced significantly higher levels of SPMs for 24 hours after the challenge compared to the controls. Not only do omega-3s play a role in mollifying the initial inflammatory response but they also help after the attack is over.
Omega-3s & ARDS Studies
One of the most serious symptoms of COVID-19 is Acute Respiratory Distress Syndrome (ARDS), which is what requires people to be put on ventilators or oxygen to survive. Adding omega-3s to a “tube-feeding” diet has been tested in ARDS patients with mixed, but potentially positive, results.
On the positive side, a recent meta-analysis of 12 randomized controlled trials on omega-3 and ARDS concluded: “In critically ill patients with ARDS, omega-3 PUFAs in enteral immunomodulatory diets may be associated with an improvement in early and late PaO2-to-FiO2 ratio*, and statistical trends exist for an improved ICU length of stay and mechanical ventilation duration. Considering these results, administering omega-3 fatty acids appears to be a reasonable strategy in ARDS.”
(*PaO2-to-FiO2 ratio is the arterial pressure of oxygen divided by the inspired fraction of oxygen and is the preferred tool to quantify the severity of the ARDS.)
Are Omega-3s In General Recommended for ‘Immune Health’?
In March this year, top researchers in the field of nutrition and immunology provided guidance on how nutrition could play a significant role during the pandemic of COVID-19. Their main suggestions were:
- Supplementation with certain micronutrients [such as vitamins A, B6, B12, C, D, E, folate, zinc, iron, selenium, magnesium, and copper] and omega-3 fatty acids is a safe, effective and low-cost strategy to help support optimal immune support.
- Supplementation above the Recommended Daily Allowance (RDA) but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted.
- Public health offices are encouraged to include nutritional strategies in their recommendations to improve public health.
- Their specific recommendation for omega-3 fatty acids was 250 mg per day as per international guidelines. (Our recommendation at OmegaQuant would be to eat a diet with enough EPA and DHA to reach and maintain an Omega-3 Index of between 8-12%. (For guidance on dosage, please use our Calculator).
A review published earlier this year examined data representing the research on prominent intervention agents such as omega-3 fatty acids, micronutrients (zinc, vitamins D and E), and functional foods including probiotics and tea components (in particular epigallocatechin gallate) for their immunological effects, working mechanisms, and clinical relevance.
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The researchers said many of these nutritive and non-nutritive food components are related in their functions to maintain or improve immune function, including inhibition of pro-inflammatory mediators, promotion of anti-inflammatory functions, modulation of cell-mediated immunity, alteration of antigen-presenting cell functions, and communication between the innate and adaptive immune systems.
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