Top 3 Nutrients for Fighting Inflammation and Autoimmunity

Inflammation is at the root of all chronic and autoimmune diseases, ranging from rheumatoid arthritis, to metabolic syndrome and diabetes, to neurodegenerative disorders and cognitive decline. With rising rates of inflammation due to poor diet, a sedentary lifestyle, and nutrient depleted soils comes rising rates of these autoimmune and chronic conditions at the population-level. Today, roughly 80 million Americans suffer from chronic illnesses that drastically affect quality of life.

While inflammation is a problem in cases of chronic disease, it is a natural bodily process designed to help us recover from injury and infection. When the body recognizes an injury or infection, it releases chemicals that trigger the immune system to either heal the damaged tissue or fight off foreign pathogens. Once the wound has been healed or the infection has been resolved, the body signals the immune system to halt the inflammatory process. However, in cases when the threat to the body is constant—or perceived to be constant—that inflammatory process never stops. Instead, it continues to wreak havoc and perpetuate more inflammation in the process.

I have written extensively about the benefits of switching to a whole foods, nutrient-dense diet and adopting a more active, less stressful lifestyle on reducing inflammation in the body. But, added support from key nutrients can also help reduce inflammation and regulate the immune system. My top three nutrients for fighting inflammation and autoimmunity are long-chain omega-3 fats EPA and DHA, curcumin, and black seed oil (also called black cumin seed oil, from the Nigella sativa plant).

What makes these three nutrients so well suited for busting inflammation and restoring balance to the immune system? What research has been done on these nutraceuticals in relation to specific autoimmune and chronic diseases? And how can you make sure you’re getting enough of these nutrients? I’ll answer these questions and more in this article.

EPA and DHA

Numerous studies have focused on the anti-inflammatory properties of EPA and DHA, long-chain omega-3 fatty acids most often found in fish oil and seafood. They work to reduce inflammation, in part, by competing for the same enzymes that pro-inflammatory compounds like arachidonic acid (AA) seek out. When sufficient EPA is present, it will out-compete AA and shift the system toward an anti-inflammatory response. Both EPA and DHA also produce metabolites like resolvins, protectins and maresins that compete with other metabolites of pro-inflammatory omega-6 fatty acids. Finally, these omega-3 fats also reduce the production of pro-inflammatory cytokines like TNF-alpha, interleukin-6, and interleukin-17.

Although our bodies are capable of producing EPA and DHA, the easiest way to get enough of these nutrients is through our diet. In theory, the human body can produce EPA and DHA endogenously from a precursor omega-3 fat alpha-linolenic acid (ALA), but in practice, our bodies are not efficient at this conversion. For some people, the conversion of ALA into DHA is less than 0.5 percent. Instead, it’s much easier to get these compounds by consuming cold-water fatty fish and shellfish, or via a supplement like fish oil.

What conditions have EPA and DHA been studied in treating?

There is a wealth of research on EPA and DHA as anti-inflammatory compounds and their role in a number of chronic and autoimmune conditions. There are thousands of studies on this topic, but some of the best well-studied conditions include rheumatoid arthritis, metabolic syndrome, and depression.

Rheumatoid arthritis

EPA and DHA have been shown to reduce inflammation, relieve pain and swelling, and improve mobility in people with rheumatoid arthritis and Lupus. In a 2020 paper, scientists reviewed decades of research on the impact of EPA and DHA on pain and inflammation in patients with rheumatoid arthritis. They found that these fatty acids reduced markers of inflammation, decreased inflammatory cytokines, relieved pain and swelling, and improved mobility. 

Multiple studies have also considered the effects of EPA and DHA on Lupus, an autoimmune disease in which the immune system targets the body’s tissues and results in widespread inflammation and organ tissue damage. Some of these studies have shown that treatment with EPA and DHA improved the quality of life for Lupus patients, prolonged their remission, reduced pain and inflammation, and significantly improved their endothelial function, which is often compromised.

Metabolic disorders

EPA and DHA have also been well-established in lowering triglycerides and blood pressure in people with metabolic syndrome. Fish oil reduces fasting triglycerides by decreasing the amount of triglyceride-rich VLDL production in the liver. It has also been shown to likely reduce blood pressure by increasing nitric oxide availability and relaxing smooth muscle.

Other studies have shown that EPA/DHA improve waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profiles in people who are overweight and/or who have pre-diabetes or diabetes. Given the prevalence of metabolic disease in our modern world, this is one of the most important benefits of fish oil.

Depression and cognitive impairment

One of the leading theories on depression is the Immune Cytokine Model of Depression. This model proposes that the chemical by-products of inflammation, called cytokines, produce various psychiatric and neurological symptoms in the brain, including depression. While it serves pharmaceutical companies to perpetuate the myth of the chemical imbalance theory of depression, the immune cytokine model is well-researched and well-established.

The evidence suggesting that EPA and DHA resolve depression is some of the most highly rated data by Examine.com. Scientists believe that EPA and DHA work against depression in a few key ways. First, omega-3s can easily permeate the brain cell membrane and interact with mood-related molecules inside the brain, applying their inflammation-reducing properties to these inflamed cells. Additionally, omega-3s themselves make up a portion of the brain cell membrane. It is possible that increasing the level of omega-3s in the brain makes it easier for serotonin, a chemical messenger specific to brian cells, to pass through these cell membranes.

As you might suspect, given that omega-3s reduce inflammation and improve cell signaling in the brain, depression isn’t the only problem they help with. EPA/DHA have also been shown to improve cognitive health, memory and focus in older adults and improve many other neurological and cognitive disorders like Parkinson’s and dementia.

Other autoimmune diseases

It is no surprise that fish oil has also shown benefits in other autoimmune diseases characterized by inflammation, including type 1 diabetes, multiple sclerosis, Crohn’s disease, and psoriasis. A 2021 systematic review of 5554 studies revealed that omega-3 and fish oils have beneficial effects on reducing the relapse rate, inflammatory markers, and improving the quality of life for patients with multiple sclerosis. Another review summarized that placebo-controlled trials of fish oil in chronic inflammatory diseases have shown decreased disease activity, and a lowered use of anti-inflammatory drugs in these and other autoimmune conditions.

How to get enough omega-3 fats, including EPA and DHA

Consuming cold-water, fatty fish like salmon, mackerel, herring, anchovies, sardines, and shellfish regularly is the preferred choice for getting EPA and DHA into the body, especially because these foods also contain other vitamins, minerals and bioavailable proteins essential for optimal function. To ensure that your diet is rich in omega-3 fats, try eating two servings of these seafoods per week. This will provide about 1 gram per day of combined EPA and DHA.

Supplementation considerations for omega-3 fatty acids

Research and my clinical experience have shown that most people do not get enough EPA and DHA from diet alone. Some people do not like the taste of seafood or are allergic, while others may not have access to fresh, reliable seafood year-round. Additionally, people with preexisting autoimmune or other chronic, inflammatory conditions may require more than the recommended 1 gram per day to see an improvement in their symptoms. In these cases, supplementing with high-quality fish oil can make a real difference. But, there are a ton of different fish oil supplements on the market today, and not all of them are worth your money. 

Purity

Because many species of fish are known to concentrate toxic chemicals like heavy metals, PCBs, and dioxins in their tissues, the purity of your fish oil supplement is essential. While these toxins are less of a problem when consuming the whole fish, they can become an issue when distilling fish oil. In fact, many fish oil supplements that claim to be free of toxins have been shown to include contaminants in independent lab testing. A good fish oil supplement is one that meets or exceeds standards like the International Fish Oil Standards (IFOS) 5-star, Global Organization for EPA and DHA (GOED) Monograph, and EU legislation.

Concentration

The overall concentration of EPA and DHA and the ratio of these compounds to one another is essential in choosing an effective fish oil supplement. I recommend between 500mg and 2 grams of combined EPA and DHA per day, depending on your diet and whether you have an autoimmune condition. For a generally anti-inflammatory supplement, research has shown that the most effective preparations contain at least 60% EPA to DHA, or a 3:2 ratio.

Freshness

I have written extensively about the dangers of oxidized, rancid oils of any kind—whether omega-6 or omega-3. They promote oxidative damage and increase inflammation, both of which are risk factors for nearly every modern disease. This is why it’s absolutely crucial to ensure that the fish oil you select is fresh and not rancid. Once it has gone rancid, it will have the exact opposite effect on your body than you want it to.

To ensure you have the freshest fish oil, check for peroxides, p-anisidine, and TOTOX. The “peroxide value” measures the rancidity reactions in the oil that have occurred during storage. IFOS and GOED standards suggest the value should be less than 5 meq/kg, but the best products will be significantly lower than that. P-anisidine is a secondary oxidation product. The IFOS and GOED standard for p-anisidine is less than 20 units. However, it’s important to note that p-anisidine is not appropriate for measuring secondary oxidation in omega-3 oils that have a strong color or contain added flavorings. TOTOX is simply a combination of the peroxide and p-anisidine values and thus is not appropriate for products with a strong color. Simply smelling or trying the product, while not a rigorous scientific method, is often the easiest way for a consumer to determine rancidity. If the product tastes or smells fishy, that can be a sign that it has oxidized. Finally, adding antioxidants to fish oil to improve stability. Some studies suggest adding curcumin and resveratrol may be a good option. 

Bioavailability

The body’s ability to absorb the beneficial components of fish oil depends on the molecular shape of the fatty acids. The more natural the shape, the more readily the body can absorb it. When it comes to fish oils, there are three forms currently available on the market:

1. Natural triglyceride oil. This is the oil you get when you “squeeze” the whole fish and extract the natural oil from it. It is the closest to eating fish oil in its natural form and is highly bioavailable. 
2. Ethyl ester oil. This is produced when natural triglyceride oil is concentrated and molecularly distilled to remove impurities. The ester form is still in a semi-natural state because it is the result of a process that naturally occurs in the body.
3. Synthetic triglyceride oil. This form occurs when natural triglycerides are converted to ethyl esters for concentration (as above), but then are re-converted into synthetic triglycerides. The original position of the triglyceride’s carbon bonds change and the molecule’s overall structure is altered, which impacts the bioavailability of the oil.

Studies on absorption of the various types of fish oil suggest that, unsurprisingly, the natural triglyceride form is absorbed better than the ethyl ester form, which in turn is absorbed better than the synthetic triglyceride form—and this is what I recommend.

Sustainability and traceability

Global fisheries have been under an enormous strain, and fish oil is a big business. It’s crucial to choose a fish oil supplement with sustainability in mind and that has a transparent and traceable supply chain. Look for products certified by organizations like Friends of the Sea or MarinTrust, two of the leading organizations for sustainable and responsible fishery management.

Curcumin

My second key nutrient for fighting inflammation is curcumin, the principal curcuminoid present in turmeric, a rhizome in the ginger family. Curcumin has been used over 4,000 years in Asian countries as a culinary spice, a component in religious ceremonies, and a therapeutic agent in Traditional Chinese Medicine and Ayurveda. While curcumin is the subject of intensive scientific research, several benefits have already been identified, including balancing and regulating the immune system, reducing oxidative stress, inhibiting inflammation, acting as an anti-coagulant, scavenging free radicals, improving neurotransmitter signaling in the brain, supporting detoxification, and altering the activities of enzymes, receptors, and related transcription factors. With such a huge list of benefits, curcumin is being used clinically to treat a variety of conditions with inflammatory underpinnings.

There is still much to learn about curcumin’s behavior in the body and its mechanisms, but we do know that it reduces inflammation in not just one, but several ways. First, it inhibits signaling pathways associated with inflammation. The most notable is the cyclooxygenase 2 (COX-2) enzyme pathway, which is responsible for the conversion of arachidonic acid to prostaglandins. This is exactly how NSAIDs like iburprofen reduce inflammation but, unlike other selective COX-2 inhibitors like NSAIDS, curcumin does this without producing significant side effects and risks, even at high doses. Second, curcumin decreases the production of several inflammatory mediators, like cytokines and chemokines. These include TNF-alpha, interleukin-6, interleukin-1B, C-reactive protein, and MCP-1. Curcumin also inhibits nuclear factor kappa, which protects and regenerates muscle and plays an important role in controlling physiological mechanisms of inflammation. These cytokines and chemokines are often elevated in chronic, inflammatory conditions like arthritis, psoriasis, and autoimmunity, and they’re the targets of medications commonly prescribed for these conditions. Third, curcumin supports the immune system by modifying the balance between Th1/Th2 and Th17/T-regulatory cells—and by regulating adaptive immunity, including macrophages, neutrophils, and dendritic cells. Numerous studies have shown that patients with autoimmune inflammatory conditions have a decreased Treg/Th17 ratio, and that improving this ratio leads to both objective and subjective measures of improvement.

What conditions has curcumin been studied in treating?

As with fish oil, curcumin has potent anti-inflammatory and anti-oxidant effects, and because virtually all chronic diseases are characterized by these factors, curcumin has been used by clinicians for a wide variety of conditions. I use curcumin the most in my practice and the research is strongest for arthritis and pain, autoimmune diseases, performance and recovery, metabolic syndrome, and cognitive function.

Arthritis and pain

Numerous studies, like those cited in a 2022 systematic review and meta-analysis, have shown that curcumin is effective for reducing inflammation, swelling and pain in inflammatory joint conditions like osteoarthritis and rheumatoid arthritis. 

A randomized controlled trial in 2014 studied 367 patients with osteoarthritis in the knee and found that curcumin was equally as effective as ibuprofen—but with far fewer gastrointestinal side effects—in treating their condition. Another 2010 study found that taking curcumin for 8 months improved osteoarthritis symptoms for 50 patients in the treatment group, who experienced improvements in several inflammatory markers. They also saw subjective improvements in pain, mobility, and quality of life. Plus, their curcumin treatment was well-tolerated with no significant adverse effects, suggesting that it is safe to take over long periods of time.

Researchers have also studied curcumin’s effects on rheumatoid arthritis patients. A systematic review of 51 studies published in 2021 found that curcumin improved clinical and inflammatory markers as well as morning stiffness, walking time, and joint swelling. Another 2021 study found that curcumin relieves symptoms of rheumatoid arthritis by reducing the expression or function of pro-inflammatory mediators nuclear factor—kB, activated protein-1, and mitogen-activated protein kinases. 

Autoimmune diseases

Curcumin has been studied as a treatment for several different autoimmune diseases, including inflammatory bowel diseases like ulcerative colitis, ankylosing spondylitis, multiple sclerosis, Lupus, psoriasis, lichen planus, type 1 diabetes, and Hashimoto’s disease. Scientists believe that curcumin’s ability to inhibit key inflammatory cytokines and associated signaling pathways in immune cells is at the root of its positive impact on all of these diseases. 

Psoriasis is one of the primary diseases being researched with curcumin interventions. This chronic inflammatory skin disease affects about 3% of the world population and results in thick, silvery plaques caused by uncontrollable proliferation of keratinocytes. In these cases, curcumin suppresses the excessive production of TNF-α by activated macrophages and impairs lipopolysaccharide (LPS) signaling. It also reduces the expression of several other inflammatory cytokines which are elevated in psoriasis cases. Patients have also reported consistent reduction in the psoriasis area and severity index (PASI), the gold standard indicator of psoriasis severity.

In cases of inflammatory bowel disease (IBD), a general term for autoimmune and autoinflammatory diseases of the intestine like Crohn’s disease and ulcerative colitis, curcumin has been shown to be an effective treatment both with and without conventional therapies. Curcumin inhibits pro-inflammatory cytokines that tend to be elevated in IBD patients and regulates Th1/Th2 and Th17/T-reg cell production, thereby balancing the immune system.

Curcumin is especially promising as a treatment for IBD because it modules the immune response in autoimmune diseases without globally suppressing the immune system. Maintaining a normal immune response is key to fighting off infection and other foreign pathogens.

Performance and recovery

In addition to its immune modulatory effects, curcumin has been shown to improve athletic performance and recovery in healthy, physically active people. Physical activity, particularly that involving high-intensity eccentric muscle contractions, produces exercise-induced muscle damage. Often, this isn’t a bad thing. It’s part of a natural hormetic response which leads to many of the positive adaptations that exercise is responsible for. But, as we age or if we overtrain, it can become more difficult to recover from this muscle damage, which can lead to decreased performance and recovery and a higher risk of injury.

Curcumin has been found to reduce the subjective perception of the intensity of muscle pain, reduce muscle damage through the decrease of creatine kinase, increase muscle performance, and have anti-inflammatory effects by modulating pro-inflammatory cytokines. It may also even have an antioxidant effect. It has also been shown to improve muscle damage, muscle soreness, inflammation, muscle strength and joint flexibility.

Metabolic syndrome

Like other diseases we have been talking about, obesity and metabolic diseases like type 2 diabetes are inflammatory conditions. As you now know, curcumin has potent anti-inflammatory and antioxidant properties, so it should come as no surprise that it can be a helpful treatment for patients with metabolic syndrome. A review of 16 trials involving roughly 1,300 patients with diabetes showed improvements in key metrics for measuring metabolic health, including fasting blood glucose levels, hemoglobin A1c, triglycerides, total cholesterol, LDL-c, HDL-c, C-reactive protein, and systolic and diastolic blood pressure.

Cognitive function

Curcumin has proven to lead to improvements in memory and attention in adults as measured by gold standard assessments and cause objective decreases in plaque and tangle accumulation in regions of the brain modulating mood and memory. Researchers saw these effects when conducting an 18-month study on 40 patients between the ages of 51 and 84 with mild cognitive impairment or a decline in cognitive performance associated with aging. These findings suggest that curcumin has anti-amyloid and anti-inflammatory effects on the brain, which may protect it from neurodegeneration. 

Supplementation considerations for curcumin

Bioavailability

Standard preparations of curcumin tend to have extremely low bioavailability due to its fast metabolic turnover in the liver and intestinal wall. Even after oral dosing, it’s likely that blood and tissues will have low concentrations of this botanical. This problem persists even at extremely high doses of curcumin—a 10-12 gram dose still results in serum levels in the low nanomolar range. 

Many methods have been used to increase the bioavailability of curcumin, including combining it with piperine and encapsulation into nanoparticles, liposomes, phytosomes, polymeric micelles, and cyclodextrins. Each of these methods has merit and leads to greater absorption and serum levels of curcuminoids and their metabolites—and thus greater efficacy. However, there is controversy about which of these methods is best. I’ve used nearly all of them in my clinical practice and now recommend adding piperine (black pepper) to curcumin, or adding crystalline curcumin in a micronized form like Theracumin. Making these additions leads to a roughly 20- to 30-fold increase in bioavailability as indicated by area under the plasma concentration-time curve (AUC). 

Other forms of curcumin have been developed in the lab specifically for their bioavailability. Novasol, a liquid, micellized form of curcumin developed in Germany is produced in a proprietary process that converts curcumin into a fully water soluble and pH stable form. The result is a biomimetic, or nature-like, micelle structure with optimal oral bioavailability. In research, Novasol has been shown to increase bioavailability by 185-fold as measured by AUC and is absorbed seven times faster.

CurcuWin and Longvida are other water soluble forms of curcumin that have been shown to increase bioavailability by 100-fold and 136-fold respectively. These are also good options, but Novasol is preferred.

Safety

Curcumin has been the subject of over 150 clinical trials over both the short- and long-term for doses as high as 8,000-12,0000 mg. Twenty double-blind trials, placebo-controlled trials and 30 other trials have found that curcumin is safe and well-tolerated when taken at recommended doses. However, there have been a few rare cases of liver toxicity or autoimmune hepatitis in people taking curcumin preparations with piperine for long periods of time, which indicates that these formulations may not be safe in the long term. Other cases of curcumin toxicity have arisen with synthetic curcumin and toxic food contaminants, underscoring the importance of choosing a reputable brand of supplement.

There are a few other precautions and contraindications to be aware of with curcumin:

• Pregnancy & breastfeeding. While turmeric is commonly used in small amounts as a spice in foods, concentrated doses of curcumin haven’t been tested. It’s best to stay on the safe side and avoid curcumin supplementation during pregnancy and lactation.
• Gallbladder problems. Curcumin can make existing gallbladder problems worse. Do not use curcumin if you have gallstones or a bile duct obstruction.
• Bleeding or coagulation issues. Curcumin is a blood thinner, so it’s best to avoid it or discuss with your doctor if you have a bleeding disorder or are already taking a prescription blood thinner.
• Other medications. Curcumin may be contraindicated with other medications, so if you’re taking a medication it’s best to check with your prescribing clinician before starting curcumin.

Black Seed Oil

Black seed, also known as black cumin or black cumin seed, comes from the Nigella sativa plant, a botanical native to the eastern Mediterranean, northern Africa, the Indian subcontinent, and Southwest Asia. It has been used as a culinary spice and a traditional medicine for at least 2,000 years and appears in writings by Hippocrates, and in Ayurvedic and Arabian systems of medicine.

Like curcumin, black seed has an almost unbelievable range of therapeutic properties. It is antioxidant, anti-inflammatory, immunomodulatory, anticancer, neuroprotective, antimicrobial, antihypertensive, cardioprotective, antidiabetic, gastroprotective (protects the gut), nephroprotective (protects the kidneys) and hepatoprotective (protects the liver). It is also a powerful antimicrobial with activity against bacteria, viruses, parasites, worms, and fungal pathogens. This explains why it has been used, both in traditional and modern medicine, for so many different diseases/conditions—from asthma and upper respiratory infections to autoimmune disease to cognitive and mood disorders to metabolic and cardiovascular disease to cancer. 

Today, the essential oil of nigella sativa, called black seed oil (BSO) or black cumin seed oil, is the most frequent application. It contains thymoquinone (TQ), thymol, carvacrol, p-cymene, nigellidine, nigellicine, and α-hederin, and fatty acids, which are mostly responsible for its pharmacological effects and therapeutic benefits. Over the last several years, BSO has been awarded “natural ingredient of the year” by a few different trade organizations because of its therapeutic potential in such a wide range of conditions, its tolerability and safety, and the huge amount of research being published about its benefits.

Like curcumin and fish oil before it, BSO fights inflammation via a number of different pathways. First, it reduces the production of pro-inflammatory cytokines like CRP, IL-6, IL-12, and TNF-α while inhibiting pro-inflammatory factors like nitric oxide, nitric oxide synthase, and COX-2. It also inhibits the release of histamine, a potent inflammatory compound related to allergies, asthma and other conditions. BSO is also a strong antioxidant, reduces reactive oxygen species, upregulates antioxidant enzymes, and has potent immunomodulatory effects by regulating Th1/Th2 and Th17/T-reg cell balance, CD4+/CD8+ differentiation, and T-lymphocyte profiles.

What conditions has black seed oil been studied in treating?

Autoimmunity

BSO has shown significant benefits in multiple autoimmune conditions, including Hashimoto’s, rheumatoid arthritis, and vitiligo, an autoimmune skin condition. In 40 patients with Hashimoto’s, BSO reduced TSH and anti-TPO antibodies while increasing T3 levels after just 8 weeks. These patients also showed a significant decrease in vascular endothelial growth factor, which is a marker of inflammation often elevated in Hashimoto’s cases. Another study found that treatment with BSO increased total antioxidant capacity, malondialdehyde, and superoxide dismutase, all of which tend to be depressed in Hashimoto’s patients. These same researchers also noted significant decreases in body mass index and improvements in endothelial function and lipid profiles.

In rheumatoid arthritis cases, BSO has shown multiple benefits, including a lower disease activity score, improved bone resorption, reductions in markers of oxidative stress and inflammation, and significant immunomodulatory activity. It also improves the immune response, especially T lymphocytes, and increases the ratio of T helper lymphocytes to suppressor T lymphocytes, increasing, in turn, the activity of NK cells.

A 2014 study evaluated both fish oil and BSO in the treatment of vitiligo and found that both led to a reduction in the Vitiligo Area Scoring Index, but that the benefits of BSO were more significant. Researchers have speculated that TQ, the primary active constituent in BSO, may have been primarily responsible for the effect since it protects cells against oxidative damage induced by a variety of free radical-generating pathologies and stimulates the production of acetylcholine, which causes the release of melanin and darkening of the skin. Other systematic reviews and meta-analyses have shown that BSO is as effective in treating a range of other skin disorders, including atopic dermatitis, eczema, warts, keratosis, psoriasis, vitiligo, infant skin infections, and acne.

Allergic and atopic disorders

Like autoimmune diseases, allergic and atopic conditions are characterized by oxidative stress and inflammation and are thus improved by inflammation-reducing compounds like BSO. These conditions are also driven by excessive histamine production and/or an inability to break down histamine after it is released. BSO reduces histamine production and stabilizes the mast cells that produce histamine, resulting in fewer allergy symptoms and better bronchial function. BSO has also shown benefits in upper respiratory infections and conditions and obstructive pulmonary diseases.

Cancer

BSO and its primary active constituents like TQ and alpha-hederin have potent anticancer and chemosensitizing effects against various types of cancer, such as liver, colon, breast, renal, cervical, lung, ovarian, pancreatic, prostate and skin tumors. BSO has been shown to reduce cell proliferation, promote cancer cell destruction, inhibit angiogenesis, and reduce metastasis. This botanical may also have a synergistic effect with chemotherapeutic drugs and radiation therapy and enhance their effects. 

Metabolic and cardiovascular dysfunction

BSO has a long history of traditional use for improving metabolic and cardiovascular function, and modern research has shown significant promise as well. For example, systematic review of 17 studies examining BSO as a treatment for patients with diabetes and other metabolic diseases found significant improvements in fasting glucose, post meal glucose, fasting insulin, Hemoglobin A1C (HbA1c), HOMA-IR.

BSO has also been shown to reduce both systolic and diastolic blood pressure in patients with hypertension. A review of RCTs and other trials found significant reduction of blood pressure in almost every patient. This study and others like it have often found that patients were able to reduce their medication doses, or in some cases stop their medication entirely, by adding BSO to their treatment regimen.

Additionally, studies have also found that BSO reduces body weight, BMI, waist-to-hip ratio, liver enzymes, triglycerides, and LDL and total cholesterol. It improves several cardiovascular risk markers, including an increase in HDL and glutathione levels, and a decrease in blood pressure, LDL/total cholesterol, and markers of oxidative stress.

Animal studies have shown that BSO significantly inhibits plaque formation in the arteries and reduces the expression of monocyte-derived macrophage growth. This is important because these macrophages have been shown to uptake oxidized LDL, becoming foam cells in the blood vessel wall, accelerating the local inflammatory response that eventually leads to atherosclerotic plaque formation.

Cognitive and neurodegenerative illnesses

BSO has been studied in a wide range of neurodegenerative diseases including Alzheimer, depression, epilepsy, Parkinsons, and traumatic brain injury. While many of these studies have been done in animals, more research in humans is underway with promising results. BSO or TQ have been shown to reduce neurotoxicity, inhibit oxidative stress, decrease beta-amyloid-induced cell damage, and improve mitochondrial function in the brain. They have a wide range of benefits in neurodegenerative conditions, including improving memory and cognition, promoting better communication between neurons, and reducing inflammation in the brain. BSO also increases GABA and reduces plasma nitrite levels in the brain, which in turn reduces anxiety symptoms. And, in animal models where depression was induced by lipopolysaccharide (LPS), an inflammatory compound, BSO reduced LPS-induced inflammation and alleviated depressive behaviors. Taken together, studies on the neuroprotective effects of BSO show its great promise for both mood and cognitive and neurological disorders.

Supplementation considerations for black seed oil

As interest in BSO grows, it’s not surprising that there has been a flood of low-quality BSO products with inferior ingredients and preparations hitting the shelves. When considering a BSO supplement, it’s important to understand the extraction method, composition and standardization to make a healthy, safe, and informed decision.

Extraction methods

Traditional herbalists have preferred using either the whole herb or a full-spectrum extract because doing so provides the full range of therapeutic compounds in the plant and leverages the synergistic relationship between these compounds. In contrast, the allopathic model tries to identify the most active ingredient, isolate it, and then amplify it. This has some merit in that it can increase the concentration of the most active ingredient and ensure a consistent and standardized dose, but it has considerable downsides, including missing out on the synergistic relationships between the active ingredient and other compounds. 

This is especially important for BSO, as it contains an array of key phytochemical compounds, including thymoquine (TQ), p-cymene, carvacrol, nigellidine, nigellicine, and α-hederin. What appears to work best in achieving a balanced and full-spectrum BSO is using freshly harvested black cumin seeds and a cold-pressed extraction. TriNutra’s patented form of BSO called ThymoQuin has done exactly that. This ingredient is made from fresh seeds with cold-pressed extraction to produce a standardized, full-spectrum oil with optimal ratios of all the bioactives found in black seeds. These precise ratios contribute to the synergistic effects available in BSO. Conversely, extractions that force high thymoquinone concentrations will often leave other beneficial compounds out or in low proportions, resulting in a narrow composition and thereby reduced therapeutic benefit.

Standardization

As you read, standardization of active ingredients is important so that you know you are getting enough to achieve the therapeutic goal. Black cumin seed naturally contains 0.3-0.7% Thymoquinone (TQ) and 25%-40% oil, but selective extraction is often used to remove part of the lipid fraction of black seed oil, which can result in less-than-optimal ratios of free fatty acids and thymoquinone, with decreased health benefits.

ThymoQuin is standardized to contain 3% TQ, with very low levels (less than 2%) of free fatty acids. This is important because high levels of free fatty acids (FFAs) interfere with BSO’s ability to reduce inflammation and oxidative stress. FFAs are a significant contributor to free radical production, destabilizing thymoquinone and triggering an inflammatory response in the body. The higher the content of FFA, the more potential for inflammation. 

Composition

The composition of active compounds in BSO is important for optimal benefits. P-cymene is a naturally occurring aromatic organic compound in BSO that creates a synergistic effect with TQ to enhance inflammation inhibition in a specific ratio (greater than or equal to 1 to 3). Carvacrol is another aromatic compound found in plants and herbs that has been shown to stabilize and enhance the inflammation inhibition ability of TQ at levels no greater than 0.1 percent.

Fortunately, TriNutra’s ThymoQuin has the optimal ratios of p-cymene:TQ and carvacrol:TQ, which is one of the reasons I think it’s the best way to get the benefits of BSO. 

Dosage

The dose range of BSO changes significantly in studies depending on whether it is taken as a full-spectrum extract or an isolated TQ. For more applications, doses of 500mg/d is suitable, which includes 15 mg of TQ if standardized to a 3% TQ content.

Safety

BSO has proven to be a remarkably safe and effective nutritional supplement when taken at appropriate doses. Studies of participants that took between 1 and 5 grams per day showed no adverse effects, and animal studies revealed no toxicity symptoms at TQ doses as high as 40 mg/kg, or roughly 250 mg of TQ or 8,333 mg of full-spectrum BSO in humans. Given that these dosages are nearly 17 times higher than the recommended 500 mg/d, BSO appears safe in these quantities.

The synergistic effects of these nutrients

Some nutrients bring out the best in others. This relationship is called “nutrient synergy,” and it happens when the properties of one nutrient increase the effectiveness of another, and vice versa. For example, vitamin K2 regulates calcium metabolism and directs it to the bones and teeth where it is needed, while keeping it out of soft tissues where it can cause harm. These nutrients exist in a synergistic relationship when consumed together. Let’s look at the synergies you can leverage between fish oil, curcumin, and black seed oil.

Fish oil and BSO

A 2020 study found that ThymoQuin, a patented black seed oil ingredient, has significant synergies with fish oil. Researchers studied the effects of both fish oil and ThymoQuin black seed oil on obesity-induced oxidative stress, inflammation, and insulin resistance and found that both supplements were effective in inhibiting or reducing these markers. However, together, a combination of fish oil and black seed oil were significantly more effective at reducing inflammation, reducing fat droplet number and size, increasing mitochondrial energy production and function, and improving cellular sensitivity to insulin. 

Fish oil and Curcumin

The synergistic relationship between fish oil and curcumin improves absorption and freshness. A 2018 randomized controlled trial also found that combining fish oil with curcumin reduced inflammatory markers like interleukin-6 and C-reactive protein in patients with migraine headaches more significantly than either fish oil or curcumin alone.

BSO and Curcumin

Co-administration of black seed oil and curcumin has been shown to lead to greater improvements in metabolic health markers like body weight and composition, lipid profiles, blood pressure, and blood glucose than either botanical independently. They have also been shown to significantly improve markers of bone health in post-menopausal women.

How these nutrients have performed in my clinical practice

In an episode of Revolution Health Radio, I talk about the efficacy of these three powerhouse nutrients in four case studies from patients I’ve seen in my clinic over the years. Click here to listen to the podcast or read the transcript.

Conclusion

Autoimmune and inflammatory conditions are incredibly and increasingly common in our modern world, and rates continue to rise each year. Our need for natural, safe and effective interventions to lower inflammation and regulate the immune system has never been higher, and fish oil, black seed oil, and curcumin are three of the most effective nutrients for this purpose. Leveraging these compounds, especially in conjunction with one another, can have real, tangible benefits for symptom relief, pain management, and improvement of quality of life.