Thread by @organichemusic

HIGH-DOSE EPA for LongCovid or ME/CFS?

Recently I spoke w/ an MD who has treated ~40 #pwLC with an Rx omega-3 fatty acid similar to EPA known as icosapent ethyl (IPE, brand name Vascepa) w/ promising results. Turns out, it may help #pwME too.

Details👇
pharmd.substack.com/p/high-dose-ep…

Even patients who had suffered from Long COVID for over two years reportedly experienced improvements in sense of taste & smell, fatigue, sleep, joint pain, brain fog, and hair/nail growth.
onlinescientificresearch.com/articles/propo…

This MD also treated ~140 acute COVID pts w/ IPE and reportedly none of them developed LC. The MITIGATE trial is currently investigating the ability of Vascepa (IPE) to reduce morbidity & mortality in a cohort of adults with URIs including SARS-CoV-2.
ncbi.nlm.nih.gov/pmc/articles/P…

A 1990 trial treated 63 post-viral fatigue syndrome pts w/ high-dose EFA. The 27 men & 36 women were on average 40 years old and had suffered from post-viral fatigue syndrome for 1 to 3 years. Their symptoms were similar to those in Long Covid and ME/CFS.
pubmed.ncbi.nlm.nih.gov/2270749/

24 pts were given placebo while 39 were given a 3-month trial of 2 g linoleic acid, 288 mg GLA, 136 mg EPA & 88 mg DHA divided into 4 daily doses. 85% vs 17% in the treatment & placebo groups reported benefit, respectively, while 0% vs 9% reported feeling worse.

In 1999, an attempt was made to replicate the above study, but this 2nd iteration seemed inferior. The sample size was smaller (50 vs 63) & a “placebo” containing 2.7 grams of linoleic acid was used. No statistically significant differences were found.
pubmed.ncbi.nlm.nih.gov/15041033/

In 2004, a small case series pub in PLEFA investigated the use of EPA in the treatment of four “chronic, intractable fatigue syndrome” patients. Pts took ~1 to 2 g EPA daily & reported significant benefits w/i 12 wks, but no objective data was collected.
pubmed.ncbi.nlm.nih.gov/15041033/

The author Dr. Puri hypothesizes that low-grade *viral persistence* inhibits the enzyme ∆-6-desaturase which is critical for EFA conversion to active metabolites like EPA & DHA as mentioned above. Past in vitro studies found that viruses do indeed inhibit this enzyme.

In fact, when viruses inhibit ∆-6-desaturase, it may cause a downstream effect that ultimately reduces the release of interferons—crucial signaling proteins that warn the body of unwanted viral presence and trigger an immune response.

I suspect that high-dose EPA or its derivative IPE may be a key to improvement in some ME/CFS and Long COVID sufferers. Furthermore, I suspect that those who have been supplementing with OTC fish oils may have missed out on potential benefits due to several reasons.

1) Oxidized/Rancid fish oil
Earlier this year, Labdoor found that 10% of the fish oil supplements they tested were rancid, with almost 50% just barely under the recommended maximum limit.
theguardian.com/environment/20…

2) Suboptimal Dosing
In the LC case studies cited above, pts improved with Vascepa (IPE) mostly in the 3 to 4 grams daily dosage range. Dr Puri recommends over 2 grams daily. However, most OTC supplements contain ~300-400 mg of EPA, only ~10% of the recommended dose.

3) EPA/IPE Monotherapy vs. EPA/DHA Combo
Multiple trials have found significant cardiovascular benefits with EPA or IPE monotherapy but no significant benefits with EPA/DHA combo therapy. See REDUCE-IT and JELIS trials vs STRENGTH trial, for example.
acc.org/latest-in-card…

4) EPA vs DHA
Past studies have illustrated that EPA and DHA may compete against each other and exert different effects. One intriguing meta-analysis investigated the efficacy of DHA/EPA supplementation in treating depression.
psychiatrist.com/jcp/depression…

Authors found that improvement correlated with dose of EPA in excess of DHA: EPA/DHA combos with ≥60% EPA improved depression on average by over 55% while lower ratios had no effect or even worsened depression.

Here are some other pertinent benefits of omega-3 fatty acids in ME/CFS and Long COVID — half of which are unique to and/or superior with EPA:
1) NO release & radical nitrogen species reduction
2) Cell Membrane stabilization
3) Immunomodulatory benefits
3) Anti-inflammation

1) EPA promotes vascular regrowth in part due to induction of nitric oxide release (NO). In fact, EPA significantly improved NO bioavailability in human endothelial cells compared to DHA. EPA also⬇️ peroxynitrite which can cause vascular dysfunction.

2) An X-ray diffraction study found that EPA and DHA exert different effects on the lipid bilayer of cell membranes. EPA readily incorporates into the cell membrane core and stabilizes it, whereas DHA does not.
ncbi.nlm.nih.gov/pmc/articles/P…

2) cont.
Why does this matter? Cell membranes are essential for cellular function, providing structural support & facilitating cell-to-cell communication + nutrient/toxin transport. Different effects of EPA & DHA on membrane stability likely elicit dif effects in cell signaling.

3) A recent study found that the omega-3 index is associated with the neutrophil-lymphocyte ratio, a biomarker for not only inflammation but also innate-adaptive immune system balance. Authors of this study did not distinguish between EPA and DHA levels.
medrxiv.org/content/10.110…

4) In a systematic review of four RCTs with 274 COVID patients, omega-3 fatty acids significantly reduced C-reactive protein (CRP, an inflammation biomarker) compared to the control group which did not receive omega-3 supplementation.
…nslational-medicine.biomedcentral.com/articles/10.11…

Summary:
1 to 2 grams twice daily of IPE or EPA for at least 12 weeks may be beneficial in some w/ Long COVID or ME/CFS, improving symptoms such as poor sleep, brain fog, exercise intolerance, smell/taste, & hair/nails. Some info on brands to consider here 👇

CAUTIONS:

In the REDUCE-IT trial, a significantly larger percentage of patients in the IPE group vs placebo group were hospitalized for atrial fibrillation or flutter (3.1% vs. 2.1%, P=0.004). The incidence of atrial fibrillation was greater in patients w/ history of AFib.

CAUTIONS:

Those with a history of AFib or atrial flutter should speak with their doctor before trialing doses above 2 g daily.

Serious bleeding events occurred in 2.7% & 2.1% of the patients in the IPE & placebo groups, respectively, which was not statis. signif (P=0.06).

CAUTIONS:

If you have a fish allergy, please be advised the products listed above are all derived from fish.

Possible side effects at higher doses include muscle or joint pain, constipation, and gout.

By the way, I got an Rx for IPE and will be starting it soon. 🤞🙏🤞

More articles cited here:
sciencedirect.com/science/articl…
plefa.com/article/S0952-…

High-dose EPA brands to consider:
(I have no affiliations with any of these companies!)

Added more brands here: