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Relieve Yourself from Excruciating Pain and Lower Inflammation NATURALLY

(The Top 9 Science-Backed NATURAL Pain-Killers and 4 Rising Stars)


Inflammation lies at the root cause of both rheumatoid and osteoarthritis and other inflammatory pain-based conditions.

Our immune system involves itself in virtually all known diseases.

[References to this Article]

As we continue exploring how our pro-inflammatory cytokines, genes, and enzymes influence our body’s inflammatory response, ONE question continues rising.

“Is there a SAFER, SMARTER, BETTER way to relieve pain, instead of NSAIDs and other toxic drugs?”

A concern with pain-killing NSAIDs, such as ibuprofen, aspirin, naproxen, and even acetaminophen, is the risk of gastrointestinal, kidney, and cardiovascular damage.

This risk is notable, because we see hospitalization and major cardiovascular event risk double in those over the age of 65, because of increased bleeding from long-term NSAID use.

So, it is reasonably appropriate to ask science for naturally non-toxic health supplements to lower our inflammation and relieve our pain.

As lowering inflammation is a core goal for all health optimizers, these are the 9 best science-backed natural anti-inflammatory options, along with 4 emerging rising stars.

#1 Curcumin



Curcumin is an extract from the ancient medicinal root, turmeric, which acts as a stimulator of brain-derived neurotrophic factor, (BDNF), a protein promoting nerve cell differentiation, growth, and survival.

The plant extract likely plays a role in mitochondria and nitric oxide support, along with an array of other noteworthy benefits.

We find an array of benefits with curcumin, with being most celebrated for its action against osteoarthritis.

UCLA medical school along with The Salk Institute, already confirming curcumin as effective for osteoarthritis in a specific form, is in trials with different curcumin forms for Alzheimer’s.

The clinical support for curcumin for major depression is as strong as any supplement or nootropic because of its effects on the COMT and MAO-A enzymes.

While curcumin kills cancer cells in a petri dish, it has low bioavailability in the human body, which places the importance of using it in a patented high absorption form.

[See Our Comparative Analysis: The Best Types of Curcumin]

Notable Curcumin Benefits

  • Aging
  • Allergies
  • Antioxidants
  • Alzheimers *
  • Cancer
  • Depression
  • Dermatitis
  • Fatty Liver Disease *
  • Hay Fever (Rhinitis)
  • Heart Disease *
  • Homocysteine
  • Inflammation
  • Nitric Oxide
  • PMS
  • Osteoarthritis
  • PMS

(* More Studies Needed)

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

IL-1beta, IL-6, IL-12, TNF-alpha, IFN-gamma, JAK-STAT, NF-kappaB, and GSK3b

Other Enzyme Targets: COMT, DAO, GPX, GST, MAO-A, MTHFR, NOS3, and PEMT


High-absorption forms only. Up to 2000 mg per day with meals.

#2 Boswellia


As a potent plant medicine, Europe classifies Boswellia extract, (Indian frankincense), from the Ayurvedic Boswellia serrata tree as a phytopharmaceutical (H15).

Clinical evidence supports the use of Boswellia against chronic inflammatory conditions, especially osteoarthritis and rheumatoid arthritis.

Studies confirm the reduction in painkiller (NSAIDs) usage with fewer emergency treatments in rheumatoid arthritis cases reporting reductions in pain, stiffness, and swelling.

In Crohn’s disease studies, Boswellia performs equally to the standard IBD drug, mesalazine.

Asthma studies also confirm the strength of Bosweillia’s clinical effects.

The four major boswellic acids which inhibit proinflammatory enzymes are β-boswellic acid (BA), acetyl-β-boswellic acid (ABA), 11-keto-β-boswellic acid (KBA), and 3-O-acetyl-11-keto-β-boswellic acid (AKBA) which shows the best effects against the widest array of inflammatory diseases.

Notable Bosweillia Benefits

  • Asthma
  • Brain Swelling and Tumors *
  • Breast Tenderness and Non-Cancerous Tumors
  • Cancer
  • Cerebral Edema
  • Cognition *
  • Crohn’s Disease
  • Diabetes *
  • Gingivitis
  • Mental Health *
  • Osteoarthritis
  • Psoriasis
  • Rheumatoid Arthritis
  • Skin Aging
  • Ulcerative Colitis

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

Similar to corticosteroids, it reduces inflammation by blocking 5-lipoxygenase. 11-keto-β-boswellic acid (KBA) is its most potent anti-inflammatory compound.


300 to 400 mg standardized extract containing 60% boswellic acids three times daily. Enhanced synergy when taken with curcumin.

#3 Pycnogenol (Pine Bark)


As a patented extract of the French maritime pine bark, Pinus pinaster, Pycnogenol is a potent antioxidant and anti-inflammatory medicinal plant.

Many claim all pine bark extracts are equal with standardization of 65–75% flavonoids, phenolic, acids, polyphenols, and procyanidins, found in blueberries, citrus, cocoa, grapes, and wine.

Recognized for its effects on nitric oxide, blood circulation and pressure, erectile dysfunction, and leg swelling, pycnogenol also appears to have significant effects on osteoarthritis and other inflammatory conditions.

Pycnogenol may turn off genes responsible for joint damage in as little as 30 minutes, as multiple studies show users taking less pain-killing NSAIDs.

Notable Pycnogenol Benefits

  • Allergies
  • Asthma
  • Autoimmune Disease
  • Blood Circulation
  • Blood Pressure
  • Cognition (“Brain Fog”)
  • Cardiovascular Disease
  • Crohn’s Disease
  • Diabetes *
  • Edema (Ankle, Feet, and Leg Swelling)
  • Erectile Dysfunction
  • Irritable Bowel Syndrome (IBS)
  • Leg Cramps and Swelling
  • Lupus *
  • Osteoarthritis
  • Varicose Veins and Ulcers

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

ADAMTS, MMP3, IL 1-beta, NF-κB, COX1, COX2, MMP3, and CRP


100 to 300 mg standardized extract per day. 1 to 3 months for best results.

#4 Cat’s Claw


Cat’s claw, uncaria tomentosa, is an anti-inflammatory Central and South American plant.

Delivering a similar mechanism as prednisone, clinical trials are finding cat’s claw to deliver potent anti-inflammatory actions, with the strongest evidence coming from studies of osteoarthritis and rheumatoid arthritis.

Blocking the release of iNOS, a free radical-creating enzyme, we believe cat’s claw might improve the immune response in a variety of conditions, possibly most especially in gastrointestinal diseases.

Cat’s claw decreases blood clotting molecules, making it unsuitable for those on anti-clotting medications or those with blood clotting disorders.

Notable Cat’s Claw Benefits

  • Anxiety *
  • Cancer *
  • Colitis *
  • Crohn’s Disease *
  • Diverticulitis *
  • Gastritis *
  • Immune stimulant *
  • “Leaky gut” *
  • Osteoarthritis
  • Rheumatoid Arthritis
  • Stomach Ulcers *

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

TNF-alpha, IL-1alpha, IL-1beta, IL-17, IL-4, COX-1, COX-2, TNF-α and NF-κB


Clinical trials show 100 to 400 mg of standardized cat’s claw extract, typically containing pentacyclic oxindole alkaloids, instead of more typical tetracyclic oxindole alkaloids. We see best results in 6 months.

#5 Omega-3’s


DHA and EPA-containing fish oil produce the most abundant anti-inflammatory evidence.

While the effects are not as notable as the previous supplements, fish oil offers the most consistent evidence to support its role as an anti-inflammatory compound.

As omega-3 deficiency is common in modern western diets, supplementation might have the greatest value in the cases of deficiencies.

Because of greater absorption and the phospholipid form, we believe krill or vegan algae oil might be the more effective omega-3 form.

Notable Fish Oil Benefits

  • Blood Circulation
  • Blood Pressure
  • Blood Thinning
  • Breast Tenderness
  • Cognition
  • Cortisol
  • Crohn’s Disease
  • DNA Damage
  • Depression (Unipolar without Anxiety)
  • Fatty Liver
  • General Inflammation
  • HDL
  • Insomnia
  • Lupus
  • Multiple Sclerosis
  • Osteoporosis
  • Oxidation
  • PMS (Painful Periods)
  • Rheumatoid Arthritis
  • Triglycerides

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

IL-6, IL-1β, TNF-alpha


Studies show a range of 1 to 4 grams daily. Fish oil may increase LDL-cholesterol in larger doses, whereas krill or vegan algae oil may lower it. We can use lower doses with krill oil.

#6 MSM


Methylsulfonylmethane (MSM) is a chemical found in animals, humans, and plants showing modest evidence of osteoarthritis benefits.

We see it in use either alone or with the lesser potent glucosamine and chondroitin.

Notable MSM Benefits

  • Colitis
  • General Inflammation
  • Leaky Gut
  • Inflammatory Bowel Disease (IBD)
  • Methylation
  • Osteoarthritis

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

IL-6, TNF-α, IL-1β, IL-8, and prostaglandin E2


Studies show 3 to 6 grams daily divided doses.)

#7 Ginger


Ginger, the ancient medicinal spice, has been in use over thousands of years for arthritis, cancer, colds, headaches, hypertension, nausea, and PMS.

Containing over 100 active compounds acting as antioxidants, ginger offers conflicting results in arthritis studies.

Ginger is arguably the strongest proven anti-nausea plant, performing equal to pharmaceutical medication in multiple studies.

Some researchers believe ginger, which contains curcumin, is synergistic with curcumin extract, and combining the two can increase anti-inflammatory benefits.

We can reason, curcumin is the actual compound providing the medicinal value.

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

(TNF-alpha, hs-CRP, COX-1, COX-2, 5- lipoxygenase, NF-κB, prostaglandin, and leukocytes)


175 to 350 standardized extract daily.

#8 Bromelain


An enzyme found in pineapples, bromelain also shows mixed results in arthritis studies.

Bromelain’s medical value for healing surgical pain and burns, along with sinusitis, is most apparent.

According to cell studies, bromelain blocks inflammatory compounds during excessive inflammation

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

COX-2, PGE-2, IL-1beta, IFN-alpha, IL-6, and TNF-alpha


400 to 2,000 mg per day.

#9 Melatonin


One superstar emerging from Coronavirus research has been melatonin.

Melatonin inhibits the NLRP3 inflammasome activation, managing the inflammatory response during the escalation of atherosclerosis, brain, liver, and lung diseases.

We believe melatonin supplementation can be a proactive step in lowering the damage of the cytokine storm syndrome, as we see hospitals using dosages in the 40 to 60 mg range with their COVID-19 patients.

Recent research shows us how melatonin is protective of all five of our major organs; the brain, heart, kidneys, liver, and stomach.

As our natural melatonin decreases with age, many medical authorities are advising its supplementation.

Notable Melatonin Benefits

  • Antioxidants
  • Blood Pressure (Nocturnal)
  • Esophagus (Lower Esophageal Pressure)
  • Gastroesophageal Reflux Disease (GERD)
  • General Inflammation
  • Insomnia
  • Insulin Sensitivity
  • Lipid Peroxidation
  • Liver Support
  • Type 1 Diabetes *
  • Multiple Sclerosis (MS)
  • Inflammatory Bowel Disease (IBD)
  • Lupus *
  • Rheumatoid Arthritis
  • Stomach Ulcers
  • Triglycerides*

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

TNF-alpha, iNOS, COX-2, LPS, MMPs, NF-κB, IL-1β, IL-6, IFN-y, IL-2, and NLRP3


Melatonin is safe in dosages up to 240 mg. Those with autoimmune diseases experience worsening of symptoms, most notably rheumatoid arthritis at dosages of 10 mg per day. We believe delayed-release melatonin is the best form for insomnia.

Notable Synergistic Anti-inflammatory Combinations

While not possessing adequate human studies for effectiveness, these notable supplements carry substantial anecdotal evidence along with cell and animal studies, and/ or initial human evidence.

Agmatine and Kratom


Being newcomers to pain and anti-inflammatory studies, both kratom and agmatine lack long-standing and large studies confirming their effects.

We should not discard these on this basis alone promising and should instead remain open to their possibility.

Similarly, the anecdotal evidence along with their ever-growing communities of users is notable and deserving of a closer look.



The metabolite of L-arginine, an amino acid, agmatine is a rising star in the pain communities.

Besides depression and possibly anxiety, agmatine might help in the fight against Alzheimer’s Disease, cognition, memory, nerve repair, seizures, and stroke.

As a strong imidazoline receptor activator, agmatine can cause increases in beta-endorphins, which act as opioid receptor activators lowering pain, stress, and fear within the adrenal glands.

It’s believed to be superior to L-arginine and L-citrulline in its unique nitric oxide influence.

Increasing the protective eNOS nitric oxide enzyme, agmatine blocks the potentially inflammatory iNOS, and neurotoxic nNOS nitric oxide enzymes.

Agmatine might indirectly block potassium channels, while directly blocking calcium channels.

We find it to be synergistic with opioids, and even opioid agonists such as kratom, increasing their pain-relieving analgesic effects while lowering tolerance.

Agmatine can be effective for neuropathic pain and is likely synergistic with marijuana for increasing this effect.

It is under investigation for alcohol and opioid withdrawal, appetite, arteriosclerosis, cancer, cholesterol, diabetes, inflammation, muscle growth (LH), and weight issues.

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

α2A, nNOS (NOS1), iNOS (NOS2), eNOS (NOS3), mTOR, NMDA, Nrf2, imidazoline, nicotinic acetylcholine


2,000 to 3,000 mg per day in divided doses.

Kratom (Mitragyna Speciosa)


As part of the coffee family, Kratom (Mitragyna speciosa) is an evergreen deciduous tree native to Southeast Asia.


[Related Article: The Kratom Top 13 List]


Much like the failed and nonscientific attacks against the kava root in the 1990s, kratom remains the subject of heavy criticism.

Despite being widely used throughout Southeast Asia for over 200 years, there is not a single documented overdose death directly attributed to the plant.

As we experience over 50,000 opioid-related deaths annually, this plant offers us an exceptionally safer opioid replacement as a solution to the growing opioid problem.

When testing the toxicity of the plant by using the LD-50 scale, it is virtually impossible to overdose on it, with caffeine and aspirin being comparatively and exponentially easier to overdose.

Kratom contains 27 alkaloids, with mitragynine and 7-hydroxymitragynine, being its two most potent.

It’s most common alkaloid, mitragynine, is a partial opioid receptor activator or agonist.

This means it indirectly targets the brain response to opioids, similar to how dairy, exercise, sugar, and sex affect the brain.

Kratom, when combined with agmatine, might deliver the single strongest pain-blocking natural combination.

The plant comes in green, red, or white vein strains causing dose-dependent effects ranging from energetic focus-stimulating to antidepressant, to pain-blocking and sedating.

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

5-HT2A, alpha 2 Adrenergic, dopamine (D1), Delta (DOR), kappa (KOR), and Mu (MOR) opioid receptors


1 to 3 grams is common for depression, energy, and focus. We see higher dosages delivering pain-relieving and sedation effects.

BPC-157 and TB-500: The “Wolverine Stack”


Another combo lacking human studies, yet anecdotally popular with supporting animal and cell studies is BPC-157, (Body Protective Complex-157) and TB-500 (thymosin beta-4), affectionately referred to as “The Wolverine Stack”.

BPC-157 and TB-500 are synthetic peptides, or compounds with two or more amino acids linked in a chain, allegedly delivering the body “regenerative” effects.

Commonly “stacked” together, the “Wolverine Stack”, is popular in the bodybuilding, nootropics, peptides, and supplements communities for injury recovery.

They promote muscle and tendon healing through new blood vessel formation, or angiogenesis, by increasing VEGF, which also might explain how they heal wounds and inflammation.

Also believed to provide healing to the gut and lower inflammation, some claim this combination can also be effective for arthritis.

Inflammatory Targets:

Cytokines, Genes, and Enzymes:

Angiogenesis (VEGF), 4‐hydroxynonenal, NOS3, serotonin, dopamine


Top Notables: akuamma, alcohol (low dose only), black seed oil, CBD, chondroitin, collagen type II, devil’s claw, L-glutamine, glucosamine, Hyaluronic acid, palmitoylethanolamide (PEA), rosehip, stinging nettle, THC, tart cherry, white willow bark, niacin B3, niacinamide B3, wild lettuce, low dose Naltexone (LDN) — (non-toxic at this dose).

Others: passionflower, algae, algae oil, astaxanthin, avocado, methylated B-complex, berries, black seed oil, borage oil, calcium, celery extract, cissus, dietary fiber, evening primrose oil, grape seed extract, green leafy vegetables, gamma-Linolenic acid, green tea, marine collagen (type I and III), matcha, moringa, olive leaf extract, olive oil, pancreatin, parsley, pterostilbene, quercetin, resveratrol, seeds, shilajit, tree nuts, vitamin A, vitamin C, vitamin D3, vitamin E, vitamin K2, zinc.

Conclusions on Anti-Inflammatory Supplements


We cannot ignore the role of inflammation in our overall health.

We should first cover melatonin and omega-3 deficiencies because it’s increasingly apparent we’ll have limited results with these critical and common deficiencies lingering.

The combination of curcumin and Boswellia appear to be the top anti-inflammatory combination addressing the root cause.

If there are peripheral issues, such as leg pain, then pine park appears to be the top choice.

Cat’s claw is an interesting option as the possible best option for auto-immune diseases.

Agmatine with kratom presents itself as the best combination for managing pain symptoms.

Your Friend in Health

Mark Stein

[Get The Essential 3 Sugars and Fat for Every Health Optimizer]