Neutraceuticals:

Omega 3 Fatty Acids (Therapeutic)

Omega-3 fatty acids are a type of polyunsaturated fat that are essential for human health but cannot be produced by the body. They must be obtained through diet or supplements. These fatty acids play a crucial role in various bodily functions, including brain health, heart health, and reducing inflammation. They are important players in the management of chronic pain.

This treatise focuses on the therapeutic benefits of omega-3 fatty acids, particularly EPA and. DHA.  As is the case with many nutritious compounds, it is often advisable to consider the use of nutrition based supplements, nutraceuticals, as an additional tool for the management of chronic pain and other conditions. Nutraceuticals are substances derived generally from food sources, with a focus on providing medicinal benefits for addressing specific health conditions.

When assessing the need for a nutraceutical, it is necessary to understand not just the immediate benefits that may be perceived when taking a supplement, but also to understand the role that a nutraceutical may have in long-term health benefits that may not be directly perceived, yet may still be valuable. This is particularly true for omega-3 fatty acids as a nutraceutical supplement with “hidden benefits.”

 

See:

Acupuncture Introduction

 

Key to Links:

  • Grey text – handout
  • Red text – another page on this website
  • Blue text – Journal publication

Definitions and Terms Related to Pain

 

Omega-3 Fatty Acids – Therapeutics

Introductory Summary

Omega-3 fatty acids, essential polyunsaturated fats including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), are renowned for their anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable in pain management (e.g., osteoarthritis, neuropathic pain) and comorbidities like cognitive function, fatigue, gut health, diabetes and obesity, cardiovascular health, anxiety, depression, insomnia, and Alzheimer’s disease.

Primarily sourced from fatty fish (salmon, mackerel), algae, flaxseeds, and walnuts, omega-3s have been used historically in diets rich in seafood for heart and brain health. Dietary sources like salmon (1,000–2,000 mg EPA/DHA per 3 oz serving) provide benefits, but to obtain those benefits consistently, it is impractical for most diets so supplementation is generally recommended.

Supplements (1,000–3,000 mg EPA/DHA/day) with high-purity formulations are essential to get the most beneficial therapeutic effects. Omega-3s are generally safe, with few of any side effects outside of occasional mild gastrointestinal upset or fishy aftertaste at high doses (>3 g/day).

This treatise explores omega-3s’ therapeutic roles, synergies, dosing, and mechanisms, tailored for pain management, for more in-depth information regarding omega fatty acids including in-depth information on omega-3’s and the foods that contain them, please see Omega Fatty Acids.

In order to gain a full understanding of the place that omega-3 fatty acids have in chronic pain and in health in general, one must be familiar with two processes intimately involved in these conditions: systemic inflammation and oxidative stress.

1. Understanding Systemic Inflammation and Oxidative Stress

“Systemic Inflammation” and “Oxidative Stress” are two conditions that contribute to chronic pain by creating a cycle of tissue damage, immune cell activation, and pain amplification. By disrupting normal cellular physiology, these conditions also contribute to the development and progression of chronic diseases, including diabetes, heart disease, stroke, chronic kidney and liver disease, rheumatoid arthritis, cancer and Alzheimer’s [8].

  • Systemic inflammation is a widespread inflammatory response throughout the body, triggered by infection, injury, stress, or other conditions. It involves the release of pro-inflammatory molecules and activation of the immune system, contributing to chronic pain and leading to various health issues. Symptoms can include increased pain, fatigue, cognitive problems, depression, decreased motivation for physical activity, and, in severe cases, organ dysfunction. While inflammation is a natural part of the healing process, chronic or excessive systemic inflammation can contribute to the development of diseases like heart disease, diabetes, and autoimmune disorders [7].

Neuroinflammation, a component of systemic inflammation, is inflammation within the central nervous system (brain and spinal cord). Systemic inflammation leads to the release of inflammatory molecules that cross the blood-brain barrier and activate immune cells in the brain, leading to or exacerbating, neuroinflammation.

Neuroinflammation contributes to the progression of acute to chronic pain. It is characterized by activation of immune cells (glial cells and astrocytes) in the nervous system that release various inflammatory chemicals like cytokines, proteases, and free radicals such as reactive oxygen (ROS), and nitrogen species (RNS). When these immune cells remain activated, neuroinflammation persists and drives chronic pain.

  • Oxidative stress is an imbalance in the body of excessive “oxidants” (oxidizing or chemically active agents, including free radicals, obtained from the diet or produced by the body) and insufficient “antioxidants” that neutralize oxidants (chemically active agents also obtained from the diet or produced by the body). Oxidative stress and chronic systemic inflammation coexist because they mutually induce each other. Oxidative stress, caused by excessive free radicals and insufficient antioxidant defenses, damages cells and tissues, including nerve cells, which leads to pain. Furthermore, this damage also triggers more inflammation, further exacerbating pain.

3. Supplements and the Anti-Inflammatory Diet

The anti-inflammatory diet emphasized at Accurate Clinic focuses on foods that help reduce inflammation and oxidative stress, potentially reducing chronic pain and the risk of chronic diseases. It emphasizes whole, unprocessed foods like fruits, vegetables, and healthy fats, while limiting or avoiding processed foods, red meat, and sugary drinks [9].

Although the anti-inflammatory diet is certainly of critical importance, even this healthy diet will not provide enough of the anti-inflammatory and antioxidant nutrients to provide the full therapeutic benefits for the many common conditions that plague patients with chronic pain. For this reason, patients are encouraged to consider taking supplements of various nutrients to gain the benefits that taking higher amounts will provide.

Additionally, as is common with many nutrients, the bioavailability of the nutritious compounds found in foods may be severely limited when simply ingested along with the foods they are found in. “Bioavailability” refers to how much of a nutrient is actually available to the body for therapeutic use after consumption.  In the absence of a formulation designed to enhance absorption and penetration into the brain and nervous system, simply eating foods that are rich in a particular nutrient may not be enough in order to gain the nutrient’s full benefits. As such, it is of value to understand the nature of enhanced formulations when considering the purchase of a nutraceutical product. Insights into enhanced formulations of nutritional supplements can be found here.

In summary, for certain nutrients found in foods it may not be enough to obtain them directly from the diet due to the relatively small amounts found in foods or they may need enhanced formulations to improve bioavailability that is not achieved by eating them in food.

4. The Role of Omega-3s in Systemic Inflammation and Oxidative Stress

  • Systemic Inflammation: Omega-3 fatty acids, particularly EPA and DHA, exert potent anti-inflammatory effects by modulating eicosanoids (local cellular hormones involved in inflammation) production and resolving inflammation. They compete with omega-6 fatty acids for incorporation into cell membranes, reducing pro-inflammatory arachidonic acid-derived mediators like prostaglandins and leukotrienes. Omega-3s promote specialized pro-resolving mediators (SPMs) such as resolvins, protectins, and maresins, which actively resolve inflammation without immunosuppression. The resolution of acute  inflammation is a critical step in avoiding the transition of acute pain (less than three months duration) associated with a new injury to becoming a chronic source of pain due to prolonged inflammation.

In clinical trials, omega-3 supplementation (1–2 gms EPA/DHA/day) significantly reduces systemic inflammatory biomarkers like CRP, IL-6, and TNF-α in conditions like rheumatoid arthritis and metabolic syndrome. An inflammatory biomarker is a measurable substance that indicates the level of inflammation in the body *systemic inflammation) and can be monitored to assess the response to a treatment. CRP is a biomarker monitored routinely in chronic pain patients at Accurate Clinic while IL-6 and TNF-α are not generally available in private medical practice due to lack of coverage by insurance.

Research

A meta-analysis of 68 random controlled trials (RCTs) showed omega-3s lower CRP by 0.5–1 mg/L, with greater effects in diabetic patients. In cardiovascular disease, omega-3s improve endothelial function by reducing vascular inflammation, lowering risk of atherosclerosis and likelihood of heart attack or stroke. Studies indicate 1 gm/day for 12 weeks decreases IL-6 by ~20% in healthy adults.

Omega-3s’ anti-inflammatory effects extend to gut health, alleviating inflammatory bowel disease (IBD) symptoms by enhancing gut barrier integrity and modulating microbiota, the microorganisms in the intestines that greatly affect chronic pain in many medical condition. 

RCTs show 2–4 gm (2000-4000mg)/day reduces remission rates in ulcerative colitis by ~30%. For pain, reduced inflammation mitigates tissue damage in OA. However, bioavailability varies; algal or fish oil forms are preferred, with enteric-coated capsules enhancing absorption. Preclinical studies suggest benefits for neuropathy by reducing NF-κB in glial cells, but human data are limited. Overall, omega-3s rank highly for systemic inflammation, with high confidence in RA and gut health, moderate for neuropathy.

  • Neuro-Inflammation: Neuroinflammation involves inflammatory cells, such as microglial and astrocytic activation in the CNS, releasing cytokines that exacerbate pain and neurodegeneration. Omega-3s, especially DHA, cross the blood-brain barrier and incorporate into neuronal membranes, modulating inflammatory pathways. DHA-derived resolvins (e.g., RvD1) inhibit microglial activation, reducing pro-inflammatory cytokines like IL-1β and TNF-α.

Research

Preclinical animal research shows DHA (100–500 mg/kg) reduces neuroinflammation in diabetic neuropathy by suppressing NF-κB and enhancing SPMs, improving nerve conduction. In DPN rat models, DHA prevents thermal hyperalgesia by reducing oxidative stress in dorsal root ganglia.

Clinical trials in multiple sclerosis (MS) patients (1–2 gm EPA/DHA/day) report reduced brain lesion activity via lowered IL-6.

For migraines, omega-3s reduce neurovascular inflammation, with RCTs showing 1 gm/day decreases frequency by ~30% via CGRP modulation (the same mechanism by which migraine prescription medication, such as Nurtec and Ubrelvy, the commonly used new migraine medication’s that have proven to be greatly effective reducing the frequency and severity of headaches, as well as aborting onset of headaches).

In Alzheimer’s, DHA (800 mg/day) has been proposed to slow cognitive decline by reducing amyloid-induced inflammation.

Bioavailability is key:  phospholipid-bound forms enhance CNS delivery. Overall, omega-3s’ role in neuroinflammation is supported, with:

      • Moderate confidence for migraines and neuropathy
      • High confidence for MS .
  • Oxidative Stress: Oxidative stress arises from excess ROS overwhelming antioxidants, damaging lipids, proteins, and DNA. Omega-3s incorporate into cell membranes, enhancing fluidity and reducing lipid peroxidation. They upregulate Nrf2, boosting SOD, catalase, and glutathione peroxidase.

Research

In diabetic peripheral neuropathy (DPN), DHA reduces ROS in Schwann cells, preventing demyelination. Preclinical studies show DHA (200 mg/kg) lowers malondialdehyde by ~25% in diabetic rats, improving nerve function. RCTs in type 2 diabetes (1 g EPA/DHA/day, 12 weeks) reduce oxidative biomarkers like 8-OHdG by ~20%.

For cardiovascular health, omega-3s lower oxidized LDL, with meta-analyses showing 1–2 gm/day reduces F2-isoprostanes by 10–15%. In OA, they protect cartilage from ROS-induced cell death.

Bioavailability: Krill oil > fish oil for absorption.

Level of Confidence

    • High confidence for metabolic and cardiovascular conditions,
    • Moderate confidence for neuropathy
  • Peripheral and Central Sensitization: Mechanisms amplifying chronic pain.

Peripheral sensitization involves nociceptor hyperexcitability due to inflammatory mediators. Omega-3s reduce this by inhibiting TRPV1 and sodium channels in DRG neurons, decreasing excitability. In DPN models, DHA (100 mg/kg) lowers sodium currents, reducing allodynia by ~30%.

Central sensitization amplifies pain via spinal glial activation. Omega-3s suppress microglia, reducing BDNF and glutamate excitotoxicity.

      • Preclinical data show EPA/DHA (1:1 ratio) attenuates NMDA receptor activity, preventing wind-up.
      • Clinical trials in fibromyalgia (2 gm/day) report reduced tenderness, with higher DHA ratios showing better outcomes in DPN (e.g., 2:1 DHA:EPA reduces symptoms more than 1:1).

Overall, omega-3s reduces sensitization, with:

      • Moderate confidence for neuropathy
      • Low for fibromyalgia
  • Transition Acute to Chronic Pain: Prevention strategies.  Transition to chronic pain involves persistent inflammation post-injury. Omega-3s prevent this by promoting resolution via SPMs. In post-surgical models, DHA (500 mg/kg) reduces IL-6, preventing hyperalgesia chronicity. In DPN, early omega-3 supplementation (1 gm/day) halts nerve damage progression. RCTs in acute injury show 2 gm/day reduces transition risk by ~20%.

Strategies: High DHA formulations (2:1 DHA:EPA) for DPN prevention. Confidence: low-moderate, preclinical dominant

5. Summary of Omega-3s: Conditions with moderate – high levels of confidence:

Neuropathic Pain Conditions

  • Peripheral Neuropathy (diabetic, chemotherapy-induced): Moderate; DHA reduces symptoms in DPN (higher DHA:EPA ratios better)
  • Fibromyalgia: Moderate; reduces tenderness .
  • Multiple Sclerosis: High; reduces lesion activity .

Inflammatory Pain Conditions

  • Osteoarthritis: High; pain reduction ~20-30% .
  • Rheumatoid Arthritis: High; lowers cytokines .
  • Crohn’s Disease/Ulcerative Colitis: Moderate; remission improvement .

Other Pain Conditions

  • Migraine Headaches: Moderate; frequency reduction ~30% .

Other Conditions

  • Cognitive Function/Enhancement: Moderate; DHA supports memory .

Mental health

  • Anxiety: Moderate; reduces symptoms, especially ≥2000 mg/d with higher DHA:EPA ratios
  • Alzheimer’s Disease: Moderate; slows decline .

Gut Health: Moderate

Metabolic Health:

  • Diabetes: High; insulin sensitivity .

Cardiovascular Health

  • Triglyceride regulation: High

6. Therapeutic Roles in Pain Conditions and Other Conditions

6a. Neuropathic Pain Conditions

  • Peripheral Neuropathy (diabetic) Omega-3s, especially DHA, show promise in DPN. RCTs (1 g EPA/DHA/day, 12 weeks) reduce pain by ~20%, improving NCV. Higher DHA:EPA ratios (e.g., 2:1) are superior, as per studies preventing neuropathy in diabetic models by reducing oxidative stress and inflammation.

    DHA addresses the multifaceted nature of DPN by modulating lipid profiles, exerting anti-inflammatory effects, directly protecting nerve cells, and influencing pathways involved in pain signaling and nerve repair.

    Moderate confidence.

    Here’s how DHA helps in DPN:

    1. Modulation of lipid profiles

    • DPN is associated with elevated levels of harmful lipids like saturated fatty acids (SFAs) and their derivatives, which can impair nerve function and contribute to inflammation.
    • DHA supplementation can help shift the lipid profile towards a more neuroprotective composition by decreasing levels of neurotoxic lipids (e.g., specific derivatives of palmitic and stearic acid) while increasing levels of beneficial lipids (e.g., DHA-containing phospholipids like DHA-PC).

    • Anti-inflammatory effects

      1. Inflammation plays a crucial role in DPN pathogenesis, with elevated levels of pro-inflammatory cytokines like TNF-α and IL-1β contributing to nerve damage and pain.
      2. DHA possesses anti-inflammatory properties, potentially reducing neuroinflammation and alleviating pain by inhibiting the production of these cytokines and modulating immune responses. One study found that DHA reduces mixed lineage kinase domain-like protein (MLKL) levels, a marker of necrosis, while increasing autophagy protein 5 (ATG5) and fatty acid-binding protein 5 (FABP5), involved in cell maintenance and repair.

    • Neuroprotection and nerve repair

      1. DHA may directly protect nerve cells from damage and improve their function.
      2. DHA can enhance nerve regeneration and functional recovery by mitigating oxidative stress, a key factor in DPN progression, according to the National Institutes of Health (NIH).
      3. DHA can interact with proteins like FABP5, which plays a role in neuronal survival and repair mechanisms, says the National Institutes of Health (NIH).

    • Modulation of excitotoxicity

      1. Overactivation of NMDA receptors by glutamate can contribute to neuropathic pain and neuronal death.
      2. DHA may help modulate the glutamatergic system towards a more neuroprotective state by decreasing glutamate levels and potentially inhibiting NMDA receptor activity.

 

  • Peripheral Neuropathy (chemotherapy-induced) For CIPN, omega-3s protect against paclitaxel damage
  • Sciatica Limited data; theoretical anti-inflammatory benefit.
  • Fibromyalgia RCTs (2 g/day) reduce tenderness via inflammation reduction. Moderate confidence .
  • Multiple Sclerosis High confidence; reduces neuroinflammation, lesion activity .

 

6b Inflammatory Pain Conditions

  • Osteoarthritis High confidence; 1–2 g/day reduces pain ~20-30% via cytokine lowering .
  • Rheumatoid Arthritis High; reduces swelling, cytokines .
  • Crohn’s Disease/Ulcerative Colitis Moderate; improves remission .

 

6c. Other Pain Conditions

  • Migraine Headaches Moderate; 1 g/day reduces frequency ~30% .

6d. Other Conditions

  • Cognitive Function/Enhancement DHA (800 mg/day) improves memory in aging. Moderate .
  • Insomnia Low; theoretical.
  • Fatigue Low.
  • Mental health
    • Anxiety: Moderate.
    • Stress: Low.
    • Depression: Low.
    • Alzheimer’s Disease: Moderate; DHA slows decline .
  • Gut Health Moderate; supports barrier in IBD .
  • Metabolic Health High; improves insulin sensitivity in diabetes .
  • Cardiovascular Health High; regulates lipids .
  • Other pertinent relevant conditions Cancer prevention: Low

7. Synergies

  • Prescription Medications: Omega-3s enhance
    1. NSAIDs in OA (1 g/day + ibuprofen, better pain relief).
    2. Gabapentin in neuropathy, may reduce oxidative stress.
    3. Caution with anticoagulants (increased bleeding at high doses)
  • Nutraceuticals:
    1. Curcumin: reduces inflammation in gut.
    2. ALA: enhances neuroprotection in DPN.
    3. Vitamin D: synergizes for metabolic health .
  • Adaptogens:
    1. Ashwagandha + omega-3s for anxiety reduction.
  • Cannabinoids:
    1. THC/CBD + omega-3s for pain via CB2.
  • Terpenes:
    1. Beta-caryophyllene enhances anti-inflammation.
  • Acupuncture:
    1. May improve OA pain.

8. Recommended Dosing

  • Dietary sources:

Dietary sources rich in the omega-3’s fatty acids, EPA and DHA (1,000–2,000 mg EPA/DHA/3 oz), are generally limited to cold water fatty fish, including sardines, salmon , mackerel, tuna, herring, and oysters. Current recommended daily intakes of EPA and DHA/day to achieve the best therapeutic benefits are in the neighborhood of 1,000 to 3,000 mg/day. This amount is rarely provided in the typical American diet, so dietary supplements are recommended.  (See: Omega Fatty Acids)

 

  • Supplement forms:

OTC forms of omega-3 supplements come in a variety of ways. First, it’s important to understand that supplementing with omega-3 fatty acids should be focused on EPA and DHA specifically, although some products may also include DPA, another omega-3 that gets converted to EPA in the body. But it is the EPA and DHA that provides the primary therapeutic benefits directed at pain, anxiety, and cardiovascular health.

Read the label carefully!

Product labeling can be very misleading. For example, the label may simply identify the product as “1000 mg fish oil” or “1000 mg omega 3.” This amount does not necessarily represent the amount of EPA and DHA specifically present in the capsule product. Also, the product may imply an amount per capsule, but upon closer reading of the label one may discover the serving size to be two capsules that is required to deliver the milligram amount presented on the label.

Read carefully as recommended dosing of omega-3’s is based ONLY on EPA and DHA, no other omega fatty acids.

Furthermore, the ratio of EPA to DHA in the product is important. The ratio of these two omega-3’s in the product may be approximately equal or there may be significantly more EPA than DHA or vice versa.

Current recommendations regarding EPA and DHA ratios suggest that when treating inflammatory conditions including arthritis and inflammatory bowel disease diseases, one should use a product with a ratio of EPA > DHA.

However, when treating the brain, central nervous system conditions or nerve conditions, including neuropathy, post-stroke, spinal cord injury, migraine headaches or anxiety, a ratio of DHA > EPA should be selected.

 

Product Sources

Krill oil: For vegetarians. EPA and DHA omega-3’s can be sourced from krill oil as opposed to fish oil. Krill oil forms may provide greater bioavailability and may avoid fishy taste

Fish oil: 1,000–2,000 mg EPA/DHA/day.

 

Higher DHA (e.g., 2:1 DHA:EPA) for DPN and anxiety (anxiolytic effects stronger with DHA-favoring ratios ≥2000 mg/d, paralleling DPN benefits). Fish/algal oil capsules.

Safety:

    1. Safe at 1–3 g/day;
    2. Fishy taste,
    3. Bleeding risk with high doses. For Eliquis (apixaban), doses ≤3 g/day EPA + DHA pose minimal bleeding risk per reviews and trials (e.g., REDUCE-IT), with slight increase in minor events (bruising) but no major bleeding. Use TAG forms ≤2 g/day or EE ≤3 g/day for safety; monitor for epistaxis. Avoid >3 g/day without supervision.

When purchasing an Omega-3, Fish or Krill Oil supplement, pay careful attention to identify the total amount of EPA + DHA  per serving (not the total Omega-3 amount).

EPA+DHA dosing to reach recommended level Omega-Check of 5.5% (or Omega-Index of 8%):

1. Diet-based recommended intakes of EPA+DHA:

  • Very low dietary intake of omega-rich foods (<3 servings/week):  
      • Consume 3000 mg/da (EPA+DHA) for12-16 weeks to correct deficiency
      • (EPA:DHA ratio ___ 1:1  or 2:1 for inflammatory pain;  ___ 1:2 for neuropathic/nerve pain or anxiety)
  • Low to moderate dietary intake of omega-rich foods (3-4 servings/week): 
      • Consume 2000 mg/day y (EPA+DHA) for12-16 weeks to correct deficiency
      • (EPA:DHA ratio ___ 1:1  or 2:1 for inflammatory pain;  ___ 1:2 for neuropathic/central pain or anxiety).

2. Omega-Check (or Omega-3 Index) -based recommended intakes of EPA + DHA:

  • Omega-Check of <3.8% (or Omega-3 of <4%):  
      • Consume 3000 mg/day (EPA+DHA) for12-16 weeks to correct deficiency
      • (EPA:DHA ratio:  ___ 1:1 or 2:1 for inflammatory pain;  ___ 1:2 for neuropathic/nerve pain or anxiety)
  • Omega-Check of 3.8-5.4% (or Omega-3 Index of 4-8%): 
      • Consume 2000 mg/day (EPA+DHA) for12-16 weeks to correct deficiency.
      • (EPA:DHA ratio: ___ 1:1 or 2:1 for inflammatory pain;  ___ 1:2 for neuropathic/nerve pain or anxiety)

Notes:

  • It may require >12-16 weeks to reach an Omega-Check of 5.5% (or an Omega-Index of 8%)
  • A dose of 1 gram/day EPA+DHA lowers serum triglycerides by about 7-10% in 2-3 weeks
  • When Omega-Check reaches  ≥5.5%  (or Omega-3 Index reaches ≥8%), dosing may be reduced to a maintenance level based also on clinical response that should be reviewed with your physician:

   Maintenance supplement dosing:

  • 1,000-1,500 mg/day (EPA+DHA) to sustain levels (may vary by body weight and diet)

Suggested brands:

Prescription: 

  1. Lovaza  (EPA-465mg / DHA-375mg) [EE] /capsule
    • Rx:  #120 tabs.  1-4 caps/day

Over the counter (OTC) – EPA>DHA:

  1. Nature Made Minis  (EPA-680mg / DHA-250mg) / 2 caps
    • Target:  $12
    • Dose: 1-6/caps/day

 

  1. Ocean Blue 2100  (EPA-1350mg/DHA-600mg /DPA-150mg) 1000mg/cap
    • Rodriguez: #120 $46
    • Dose: 1-3 caps/day

Over the counter (OTC) – DHA>EPA:

  1. Thorne Advanced  DHA (EPA-200mg / DHA-650mg)/ 2 caps
    • Doctor Supplement Store (DSS): 60 tabs) $22
    • Dose: 2-6/caps/Day

9. Bioavailability and Recommended Formulations

  • Bioavailability: High for EPA/DHA (~90%); ALA converts poorly (~5–10%) .
  • Formulations: Fish oil (more affordable), krill oil (better absorption), algal (vegan).
  • Practical tips: Take with meals; refrigerate to prevent oxidation.

10a. Mechanisms of Action (Patient-Friendly Explanation)

Omega-3s reduce swelling, protect nerves from damage, and balance brain chemicals, easing pain and improving health.

10b Detailed Mechanisms of Action 

Omega-3s incorporate into membranes, reducing arachidonic acid-derived mediators. DHA in DPN: Reduces sodium currents, increases potassium currents in DRG neurons; generates resolvins for inflammation resolution

11. Levels of Confidence 

Determining Levels of Confidence

Levels of confidence are determined by the hierarchy of research study designs:

  • Randomized Controlled Trials (RCTs): High confidence (e.g., a drug for diabetic neuropathy [1]). Randomized Controlled Trials (RCTs) involve human participants who are randomly assigned to different groups (treatment or control) to test the effectiveness of an intervention.Limitations: Short duration.
  • Systematic Reviews/Meta-Analyses: Highest confidence (e.g., diabetic neuropathy meta-analysis [1]).
  • Cochrane Reviews: Gold-standard systematic reviews.
  • Other Studies: Observational, preclinical; lower confidence (e.g., acute pain [4]). Confidence is rated High (robust RCTs, meta-analyses), Moderate (small RCTs, observational), or Low (preclinical, case reports).

Levels of Confidence in Omega-3s research

  • Systemic Inflammation: High; lowers CRP/IL-6 .
  • Neuro-Inflammation: Moderate; reduces glial activation .
  • Oxidative Stress: High; boosts antioxidants .
  • Peripheral/Central Sensitization: Moderate; modulates ion channels .
  • Transition Acute to Chronic Pain: Moderate; resolves inflammation .
  • Other conditions: As in section 5.

12. Chemistry and Sources (up to 200 words per subsection)

  • Chemical structure: EPA (C20:5 n-3), DHA (C22:6 n-3); long-chain PUFAs.
  • Primary dietary sources: Salmon (1–2 g/3 oz), flaxseeds (ALA 2 g/Tbsp).

13. References

  1. https://pmc.ncbi.nlm.nih.gov/articles/PMC10324313/
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC5875591/
  3. https://www.medcentral.com/pain/chronic/omega-3-fatty-acids-neuropathic-pain
  4. https://www.mdpi.com/2227-9059/13/7/1607
  5. https://www.dovepress.com/omega-3-polyunsaturated-fatty-acids-effect-on-neuropathy-of-the-periph-peer-reviewed-fulltext-article-DMSO
  6. https://www.sciencedirect.com/science/article/pii/S0952327822000680
  7. https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-12-355
  8. https://www.sciencedirect.com/science/article/pii/S0005273617301566
  9. https://www.ahajournals.org/doi/10.1161/cir.0000000000000482
  10. https://www.dovepress.com/effects-of-omega-3-polyunsaturated-fatty-acid-supplementation-on-neuro-peer-reviewed-fulltext-article-DMSO
  11. https://www.researchgate.net/publication/393191161_Omega-3_Polyunsaturated_Fatty_Acids_PUFAs_and_Diabetic_Peripheral_Neuropathy_A_Pre-Clinical_Study_Examining_the_Effect_of_Omega-3_PUFAs_from_Fish_Oil_Krill_Oil_Algae_or_Pharmaceutical-derived_Ethyl_Es
  12. https://www.droracle.ai/articles/32703/if-a-fish-oil-supplement-reports-3600-mg-fish-oil-1296-mg-epa-and-864dha-would-it-be-ok-for-a-person-with-peripheral-neuropathy-to-take-two-of-these-a-day-or-is-that-too-high-of-a-dose-and-if-it-is-too-high-of-a-dose-what-would-be-expected-in-terms-of-side-effects
  13. https://www.researchgate.net/figure/Effect-of-omega-6-and-omega-3-PUFA-on-diabetic-peripheral-neuropathy_fig1_327227653
  14. https://www.lifeextension.com/magazine/2020/3/new-hope-for-diabetic-neuropathy
  15. https://pubmed.ncbi.nlm.nih.gov/40015508/
  16. https://ascopubs.org/doi/10.1200/jco.2014.32.15_suppl.5019
  17. https://pubmed.ncbi.nlm.nih.gov/22894640/
  18. https://www.clinicaltrials.gov/study/NCT01049295
  19. https://onf.ons.org/sites/default/files/2025-05/pn-evaluation-table_omega-3-2025.pdf
  20. https://ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.tps9643
  21. https://journals.lww.com/md-journal/fulltext/2020/12110/prevention_of_oxaliplatin_related_neurotoxicity_by.93.aspx
  22. https://research.bond.edu.au/en/publications/the-effect-of-oral-omega-3-polyunsaturated-fatty-acid-supplementa-2
  23. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00723/full
  24. https://www.pmc.ncbi.nlm.nih.gov/articles/PMC5875591/

14. Patient Handout

Omega-3 Fatty Acids: Your Natural Pain and Inflammation Reliever

What are Omega-3s?Omega-3s are healthy fats in fish, seeds, and algae, helping reduce swelling and protect nerves.

How Do They Help? (List pain conditions, pain-related conditions, other conditions, including cognitive function, fatigue, gut health, metabolic health, cardiovascular health.) (up to 500 words)

  • Joint Pain: Reduces osteoarthritis pain.
  • Nerve Pain: Improves diabetic neuropathy, especially DHA; protects against chemotherapy-induced neuropathy; may benefit idiopathic neuropathy.
  • Headaches: Lowers migraine frequency.
  • Mood: Eases anxiety/depression.
  • Brain Health: Boosts memory, slows Alzheimer’s.
  • Gut Health: Supports IBD.
  • Heart Health: Lowers cholesterol/blood pressure.
  • Metabolic Health: Improves blood sugar.
  • Fatigue: Boosts energy.

How to Get Them? (Dietary sources, supplements, preparation, dosage.)

  • Diet: Salmon (1–2 g/3 oz), flaxseeds (2 g ALA/Tbsp).
  • Supplements: 1,000–2,000 mg EPA/DHA/day; higher DHA for neuropathy.
  • Safety and side effects.Mild stomach upset; check with doctor if on blood thinners.

Tips for best results (e.g., food synergies, acupuncture).Take with meals; combine with curcumin; try acupuncture for OA.

Contact information for Accurate Clinic.Accurate Clinic: (504) 475-2225 | www.accurateclinic.com

 

Next Step:

  • ALA next for neuropathy focus.

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

 

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

For more information, please contact Accurate Clinic.

 

Supplements recommended by Dr. Ehlenberger may be purchased commercially online

Please read about our statement regarding the sale of products recommended by Dr. Ehlenberger.

 

 

.