Inflammation itself is not a disease, but is featured, to varying degrees, in adverse health conditions. What follows is a summary of dietary and supplemental approaches to addressing general chronic inflammation and para-inflammation. As many types of general inflammation often occur without additional symptoms, most of the strategies listed below are based on their ability to reduce circulating inflammatory cytokines, the hallmark of the para-inflammatory state
Macronutrients and Energy Balance.
Macronutrient content (particularly the types and levels of carbohydrates and fats) can have a significant effect on the progression of inflammation (as measured by increases in pro-inflammatory markers). Diets with relatively high glycemic index (GI) and glycemic load (GL) have been associated with elevated risk of coronary heart disease, stroke, and type 2 diabetes mellitus, particularly among overweight individuals, and have been associated with modest increases in pro-inflammatory markers in multiple studies. As discussed previously, some dietary fats (particularly saturated and synthetic trans- fats) increase inflammation occurrence, while omega-3 polyunsaturated fats appear to be anti-inflammatory. Since fat tissue (especially abdominal fat) expresses inflammatory cytokines, obesity can be a major cause of low-grade, systemic inflammation. Thus, it is important that total energy intake be proportional to energy expenditure, to avoid the deposition of abdominal fat. Obesity-induced increases in inflammatory cytokines appear to be reversible with fat loss. In a dramatic example, weight loss in a group of 20 severely obese individuals reduced IL-6 by 22% and CRP by almost 50%.
Amongst the most anti-inflammatory nutrients (based on the model and study data) are magnesium, beta-carotene, turmeric (curcumin), genistein, and tea. The most pro-inflammatory included carbohydrates, total- and saturated fat, and cholesterol. The index may provide a useful metric for accessing the overall inflammatory potential of an individual diet.
Exercise. Energy expenditure through exercise lowers multiple cytokines and pro-inflammatory molecules independently of weight loss. While muscle contraction initially results in a pro-inflammatory state, it paradoxically lowers systemic inflammation.
Fiber. In an analysis of 7 studies on the relationship between weight loss and hs-CRP, increased fiber consumption correlated with significantly greater reductions in hs-CRP concentrations.
Magnesium. There is significant association between greater dietary magnesium and the lower levels of the inflammation-associated proteins homocysteine and fibrinogen. Magnesium was rated as the most anti-inflammatory dietary factor in the Dietary Inflammatory index, which rated 42 common dietary constituents on their ability to reduce CRP levels based on human and animal experimental and observation data.
Vitamin D. Vitamin D appears to exert anti-inflammatory activity by the suppression of pro-inflammatory prostaglandins, and inhibition of the inflammatory mediator NF-κβ. Vitamin D deficiencies are more common amongst patients with inflammatory diseases (including rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and diabetes) than in healthy individuals. They also occur more frequently in populations that are prone to low-level inflammation, such as obese individuals and the elderly.
Vitamin E. Vitamin E functions as an antioxidant in the body. Specifically, vitamin E is incorporated into low-density lipoprotein (LDL) particles and protects them against oxidative damage; it seems to guard against atherosclerosis via other mechanisms as well. The gamma-tocopherol form of vitamin E appears to complement the anti-inflammatory action of alpha-tocopherol. The combination of alpha-tocopherol and gamma-tocopherol supplementation appears to be superior to either supplementation alone on biomarkers of oxidative stress and inflammation.
Other Dietary Factors
Resveratrol and Pterostilbene. The exact mechanism by which resveratrol exerts anti-inflammatory activity has not been established, although it inhibits a variety of pro-inflammatory compounds (cyclooxygenase, TNF-α, IL-1β, IL-6, NF-κβ) in animal models and human cell culture. Resveratrol may be protective against general, low-level para-inflammation as well: when taken with a single high-fat, high-carbohydrate meal (930 kcal), resveratrol (100 mg) prevented the sharp post-meal increases in markers of oxidation and inflammation in a small crossover study of 10 healthy volunteers.
Curcumin. Extensive in vitro and animal studies have examined the effects of curcumin on experimentally-induced inflammatory diseases (atherosclerosis, arthritis, diabetes, liver disease, gastrointestinal disorders, and cancers) and disease markers (lipoxygenase, cyclooxygenase, TNF-α, IL-1β, NF-κβ, and others). Most of the small randomized controlled trials of curcumin have consistently shown patient improvements in several inflammatory diseases, including psoriasis, irritable bowel syndrome, rheumatoid arthritis, and inflammatory eye disease.
Tea polyphenols. The anti-inflammatory effects of green and black tea polyphenols have been substantiated by dozens of in vitro and animal studies. In clinical interventions, black tea appears to be more successful in reducing inflammatory markers than green tea. A 25% reduction in CRP was also observed in a small trial of healthy, non-smoking men consuming a black tea extract (equivalent to 4 cups of tea/day) for 6 weeks. A similar average reduction was observed in a larger study of healthy, individuals at high risk for coronary heart disease, but revealed a more dramatic 40-50% reduction in CRP amongst individuals with the highest starting CRP values (>3 mg/L).
Carotenoids. In the Women’s Health and Aging Study, participants with the highest blood levels of α-carotene and total carotenoids were significantly more likely to have the lower IL-6 levels than participants with low carotenoid levels at the onset of the study. Participants with the lowest blood levels of α- and β-carotene, lutein/zeaxanthin, or total carotenoids were more likely to experience increases in IL-6 over a period of 2 years.
DHEA. Low levels of sex hormones are associated with systemic increases in inflammatory markers; DHEA (dehydroepiandrosterone) is an adrenal steroid hormone, the precursor to the sex steroids testosterone and estrogen. DHEA is abundant in youth, but steady declines with advancing age and may be partially responsible for age-related decreases sex steroids. In cell culture and animal models, DHEA can suppress inflammatory cytokine activity, in some cases more effectively than either testosterone or estrogen. Chronic inflammation may itself reduce DHEA levels. DHEA supplementation in elderly volunteers (50 mg/day for 2 years) significantly decreased TNF-α and IL-6 levels, as well as lowered visceral fat mass and improved glucose tolerance (both associated with inflammation).
Fish Oil. This is the best source of the omega-3 fatty acids eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) that can only be synthesized to a limited extent in humans, which is why fish oil supplementation is so critical. Omega-3 fatty acids have been well studied for their prevention of cardiovascular disease and mortality in tens of thousands of patients; the anti-inflammatory effects of omega-3’s contribute to this activity. It has also been successfully proven to improving patient outcomes in scores of studies of other inflammatory diseases, particularly asthma, inflammatory bowel disease, and rheumatoid arthritis.
The association between greater fish oil/omega-3 consumption and reduced systemic inflammation is substantiated by data from several large observational trials. In 855 healthy participants from the Health Professionals Follow-Up Study, intake of omega-3 fatty acids was associated with lower plasma levels of markers of TNF-α activity; interestingly, high intake of both omega-3 and omega-6 fatty acids (which are usually assumed to be pro-inflammatory) was associated with the lowest level of inflammation. The Nurses’ Health Study I cohort of 727 women revealed lower concentrations of inflammatory markers (including CRP and IL-6) amongst those in the top 20% of omega-3 consumption, when compared to those who consumed least amount. In the ATTICA study of over 3000 Greek men and women without any evidence of cardiovascular disease, participants who consumed over 300g of fish per week had, on average, 33% lower CRP, 33% lower IL-6, and 21% lower TNF-α than participants who did not consume fish. In a sample of 5,677 men and women without cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, long-chain omega-3 intake (from fish or supplements) was associated with reduced plasma concentrations of multiple inflammatory markers (including CRP, IL-6, and TNF-α receptor, a measure of TNF-α activity).
N-acetyl cysteine (NAC). Activation of the NF-κB pathway plays a central role in the activation of inflammatory cytokine genes; N-acetyl cysteine inhibits NF-κβ in cell culture, lowering expression of cytokines such as IL-6 and IL-8. Data establishing the effects of NAC on lowering chronic inflammation in humans is limited, but shows promise. NAC supplementation for 8 weeks demonstrated modest, but statistically significant decreases in circulating IL-6 levels in patients with chronic kidney disease. The effects were more pronounced in persons with significant inflammation at the start of the study (as measured by hs-CRP). NAC also reduced markers of systemic inflammation in a small study of patients with burn injuries.
Boswellia. Boswellia serrata (frankincense) is a traditional anti-arthritic in Ayurvedic medicine; its anti-inflammatory properties have been attributed to the specific inhibition of 5-LOX and reduction in the production of pro-inflammatory leukotrienes by boswellic acids, a constituent of the Boswellia gum resin.
Bromelain. The anti-inflammatory activity of the proteolytic enzyme preparation bromelain has been attributed to its ability to reduce COX-2 activity, decrease prostaglandin and thromboxane synthesis, lower circulating fibrinogen levels, and reduce cellular adhesion of pro-inflammatory white blood cells to the sites of inflammation. Another study comparing a standardized commercial enzyme preparation containing bromelain with diclofenac reached the same conclusion. The study reported that the supplement containing bromelain (90 mg, three times daily) to be as effective as diclofenac (50 mg, twice daily) in improving the symptoms of osteoarthritis of the knee. Patients reported comparable reductions in joint tenderness, pain and swelling, and improvement in range of motion at the end of the study. The investigators found bromelain to be as good as diclofenac on a standard pain assessment scale and to be better than the drug in reducing pain at rest.