Daily Nutrient Intake and Inflammation Among US Adults

Introduction

Inflammation has long been linked to the development and progression chronic diseases like cardiovascular disease (CVD), cancer, diabetes and chronic kidney disease as well as mortality.^1–5 Many environmental factors can elevate inflammation, and given its associated with a wide variety of chronic diseases including behavioral health conditions, inflammation is a likely target for prevention of chronic diseases besides CVD.¹ Even the hyperinflammation during an initial severe COVID-19 episode has been associated with an increased downstream mortality risk from all causes.⁶ Although some treatments have been suggested as ways to decrease inflammation and prevent negative health outcomes, many of those treatments like corticosteroids have negative outcomes over the long term.⁷ Consequently, dietary and nutrition-based strategies have been proposed by many authors.⁸ In fact, the mass media has many articles and advice for patients on decreasing inflammation through diet.^9,10

For the consumer, it is difficult to apply the clinical benefits of nutrients in chronic disease to their diet because most study designs are not truly translational.¹¹ A problem with many of the studies that support foods as anti-inflammatory is that they provide evidence of biological plausibility but do not actually link data from human diets to clinical measures of inflammation.⁸ Further, many of the foods identified as anti-inflammatory contain multiple nutrients with professed anti-inflammatory properties, so linking any one nutrient in a supposedly anti-inflammatory food may be promoting the wrong nutrient.^12,13 The Nutrition Facts panel on packaged foods has been a way for patients to see the percent Daily Value (%DV), a reference established by the United States (US) Food and Drug Administration (FDA) to guide dietary consumption of key nutrients. What is unclear is whether the nutrient intake of US adults is associated with inflammation. While studies have used the National Health and Nutrition Examination Survey (NHANES) to examine the anti-inflammatory potential of nutrient intake, these studies were limited in nutrients, did not standardize nutrient intake relative to the Daily Value (DV), and used hematologic inflammatory indices that lack the established clinical relevance of high-sensitivity C-reactive protein (hs-CRP) as an inflammatory biomarker.¹⁴

We undertook a nationally representative secondary analysis of nutrient intake in US adults for purported anti-inflammatory nutrients by measuring current inflammation with hs-CRP. Purported anti-inflammatory nutrient intake was quantified based on DVs to make results relevant to the Nutrition Facts panel.

Methods

The data were obtained from the NHANES 2021–2023 dietary survey and laboratory test datasets. NHANES employs a stratified, multistage probability sampling design to generate estimates representative of the noninstitutionalized US population. Detailed information on the 2021–2023 survey design, including the dataset analyzed during the current study, is available in the NHANES documentation.¹⁵ The 2021–2023 NHANES baseline included 4,963 participants aged 18 years and older, representing approximately 236 million US adults. All analyses were conducted using the survey package in R version 4.3.3 (R Foundation for Statistical Computing), which accounts for NHANES’s complex sampling design and provides population-level estimates.

Results

Table 1 shows the demographic distribution of the study population as well as their mean hs-CRP and caloric intake. A little over half of the study population was female, and participants were evenly distributed across age groups, with approximately one-third in each of the following categories: 18–39, 40–59, and ≥60 years. Those identifying as non-Hispanic Black, Hispanic, and Other, made up 11%, 17%, and 10% of the cohort, respectively. Thirteen percent of the cohort had an income-poverty ratio less than one.

Table 2 demonstrates the relation of nutrient intakes to hs-CRP by low (≥10% below the DV), moderate (includes the DV), and high (≥10% above the DV) intake. High intake of dietary fiber, folate, magnesium, and vitamins B6, C, D, and K were all significantly associated with relatively lower levels of hs-CRP when compared to low intake of these nutrients in Kruskal–Wallis rank-sum test, potentially linking them to levels of inflammation. The associations between low and high intakes of vitamin B12 and zinc with hs-CRP were present only in the ANOVA analysis but not in the Kruskal-Wallis testing, resulting in a conclusion of no significant association between these nutrients and inflammation. High intake of Vitamin D achieved the lowest mean hs-CRP and <2 mg/L. Of note, no association was demonstrated for vitamin E in either set of tests.

Discussion

Rather than speculating on the biological plausibility of certain nutrients affecting inflammation, this study uses a nationally representative sample to show the relationship between nutrients and inflammation by converting individuals’ diets into nutrient intakes relative to %DV on the Nutrition Facts panels of packaged foods. Further, the nutrient intake and current state of hs-CRP are measured very close in time, strengthening their linkage. Most of the nutrients proposed to be anti-inflammatory showed a profile consistent with that contention, although several, like vitamin E, did not.

It is important to recognize that for many of the nutrients, the anti-inflammatory effect occurred at intake levels ≥10% above the recommended value. For example, the significant drop in inflammation for folate and vitamin D is only evident in the high intake group. For others like dietary fiber and magnesium, the drop in inflammation is also seen between low intake and moderate intake which includes the DV. Patients can modify their diets to incorporate more of these anti-inflammatory nutrients as a strategy to modify their levels of inflammation. This would be particularly important for those experiencing poverty where inflammation has a synergistic effect on their mortality risk.² Additional studies are needed to demonstrate a cause-and-effect relationship between nutrient intake and inflammation that extends to patient-oriented outcomes of interest for specific chronic diseases, which would then have clinical implications for DVs and patient counseling with respect to dietary composition.

An additional strength of this study is that it focuses on nutrient levels that come from whole foods dietary intake and not from supplements. There may be advantages of obtaining nutrients through dietary intake rather than supplements,¹¹ and the evidence concerning the impact on inflammation from nutritional supplements is conflicting.^31,32 Interestingly, Vitamin D was the only nutrient to achieve a mean hs-CRP below the risk enhancer threshold for CVD. It is important to note that while hs-CRP has been reported as a strong independent risk factor for CVD based on <1 mg/L (low risk), 1 to <3 mg/L (average risk), and ≥3 mg/L (high risk),³³ it is a clinically useful cardiovascular risk predictor across a full range of values,³⁴ and more recent American Heart Association guidelines incorporate it as a risk enhancer in select individuals when >2 mg/L.³⁵ Moreover, inflammation has an effect on a large number of chronic diseases,¹ so despite not all statistically significant hs-CRP reductions being below the low cardiovascular risk range, there is still clinical relevance in addition to cardiovascular risk reduction. Future studies are needed to determine how much clinical benefit these inflammatory reductions confer in a variety of chronic diseases.

There are limitations to this study. First, this study is based, in part, on two days of 24-hour dietary recall, thereby making the dietary intake retrospective data with the potential for recall bias. However, the subjects write down and recall all foods and beverages consumed the days before the interview (midnight to midnight). They are also given measuring cups, spoons and other guides to know how much they ate. This short duration in time between when the participant ate and when it was written down decreases the likelihood of recall bias. Furthermore, while it is possible that the surveyed individual’s diet differed during the day of recall from other days, this dietary recall is a standard measure of dietary intake used by the US Department of Agriculture. Second, we used hs-CRP as a measure of inflammation. hs-CRP has substantial reliability and validity as a commonly used clinical measure of chronic low-grade inflammation.^36,37 It is possible that the results might differ with other measures of inflammation. A third limitation is that sun or other ultraviolet radiation B (UVB) exposure can affect Vitamin D status, and while NHANES does not allow for such exposure to be controlled, it is unlikely that such exposure differs widely across the entire US population. A fourth limitation is that we computed these relationships for the entire population without removing individuals with chronic inflammatory conditions or behavioral factors like tobacco smoking or heavy alcohol use that could also potentially impact hs-CRP levels. NHANES does not report on inflammatory conditions (e.g., lupus, plaque psoriasis, Crohn’s disease, or inflammatory bowel disease), and a host of environmental factors, including diet, make up the mechanistic pathway through inflammation to disease.¹ Therefore, this study is still able to provide important information from US adults regarding what nutrients are anti-inflammatory that could help guide the diet and exercise advice provided in primary care.

Conclusion

Regular dietary intake is associated with clinically measurable inflammation in a nutrient-specific manner. Dietary fiber and magnesium reduce inflammation when dietary recommendations are met; however, some nutrients like folate and vitamin D are only associated with anti-inflammatory benefits above recommended values. Given chronic inflammation’s association with morbidity and mortality, randomized-controlled trials are needed to evaluate whether DVs warrant adjustment, particularly for nutrients that may require higher than DV recommended intake to achieve reduced inflammation. Future trials of the anti-inflammatory impact of different nutrients would need to adhere to a whole diet nutrition model since supplements are generally not effective and whole foods contain multiple nutrients. In the meantime, dietary approaches focusing on these nutrients may help individuals lower hs-CRP and potentially mitigate inflammation-related health risks.

This article was externally peer reviewed.