Phytic acid, also known as inositol hexakisphosphate or IP6, is found in grains, oil seeds, legumes and nuts as the primary storage form of phosphorus, storing as much as 80% of phosphorus [1
]. In its salt form, it is referred to as phytate. Phytic acid is a well-known inhibitor of zinc and iron absorption [2
]. For this reason, its consumption is a concern, particularly in developing countries where these micronutrient deficiencies are rife. Despite its adverse effect on mineral absorption, phytic acid is also a potent anti-oxidant implying strong health benefits. In animal and cell culture studies, it was shown to have anti-neoplastic properties in various types of cancer including breast, colon, liver and prostate cancer, as well as anti-inflammatory properties [6
]. The health benefits of phytic acid are largely attributed to its anti-oxidant properties. Phytic acid has a strong affinity for iron and can chelate free iron, thus preventing iron-related free radical formation and oxidative damage [11
]. As part of the human body’s normal cellular metabolism, free radicals are generated and are important for the activation of various metabolic pathways. However, a healthy balance between free radical generation and the availability of anti-oxidants is necessary to prevent oxidative stress, which can lead to various adverse health outcomes including diabetes, cancer, cardiovascular diseases (CVDs) and inflammation [12
]. Dietary anti-oxidants are important in maintaining this balance and thus preventing inflammation. C-reactive protein (CRP) is a well-studied, non-specific inflammation marker that is synthesized mainly in hepatocytes. CRP is elevated in various health conditions such as obesity and insulin resistance, and higher levels are also associated with an increased risk of developing CVDs and diabetes [13
]. Despite the numerous studies in animals and cell culture on the health benefits of phytic acid, there is a dearth of information on the association of dietary phytic acid intake and markers of inflammation in a population-level study. This study focuses on individuals with overweight and obesity because obesity is associated with low grade chronic inflammation marked by increased production of adipocyte cytokines, leading to an increase in hepatic CRP production [19
]. The aim of the study was to investigate the association between phytate intake and CRP concentration among subjects 20 years and older that were classified as overweight or obese in the National Health and Nutrition Examination Survey (NHANES), using the 2009/2010 survey cycle. Due to its anti-oxidant properties, I hypothesized that phytate intake would be associated with lower odds of elevated CRP concentration among the study population.
After adjusting for sampling weight, strata, and PSU, 45% of the subjects were female and 55% were male, as seen in Table 1
. Most of the subjects (68%) were non-Hispanic Whites, with 10% and 11% being Mexican Americans and non-Hispanic Blacks, respectively. Among the study subjects, 57% never smoked, 15% were current smokers and the remaining 28% were former smokers.
The median (with 95% CIs) phytate intake for all subjects was 0.66 (0.64, 0.68) g/d, as seen in Table 2
. Median phytate intake was significantly higher among men than among women (p
< 0.0001). Among the different ethnicity groups, non-Hispanic Whites had significantly higher phytate intake than both non-Hispanic Blacks and Mexican Americans (p
< 0.0167 for both). Current smokers had lower phytate intake than both non-smokers and former smokers (p
< 0.0167). The median (with 95% CIs) CRP concentration for all subjects was 1.4 (1.2, 1.5) mg/L. It was higher among women compared to men (p
= 0.001), but did not differ by ethnicity or smoking status. Individuals with a history of at least one of the medical conditions identified in the methods section had higher CRP concentrations than those with no history (p
= 0.0001) and former users of any kind of HRT had a significantly higher median CRP than those who have never used HRT (p
When subjects were classified as having a normal or elevated CRP concentration (CRP >3 mg/L), CRP was elevated in 32% of subjects. Elevated CRP concentrations were observed in 42% of female subjects compared to 23% of males (OR = 2.4; 95% CI = 2.0, 2.9; p
< 0.0001; see Table 3
). Non-Hispanic blacks had higher odds of elevated CRP compared to non-Hispanic Whites (OR = 1.58; 95% CI = 1.28, 1.96; p
= 0.001). Current smokers also had higher odds of elevated CRP compared to those who have never smoked (OR = 1.27; 95% CI = 1.04, 1.55; p
= 0.03), and former HRT users had significantly higher odds of elevated CRP compared to those who never used HRT (OR = 2.09; 95% CI = 1.59, 2.76; p
< 0.0001). Both phytate intake (OR = 0.69; 95% CI = 0.59, 0.81; p
= 0.0005) and fiber intake (OR = 0.98; 95% CI = 0.97, 0.98; p
< 0.0001) were associated with reduced odds of elevated CRP concentration in their respective logistic regression equations.
In the multiple logistic regression model (Table 4
), phytate intake, sex and smoking status were significantly associated with the odds of elevated CRP. Higher phytate intake was associated with lower odds of elevated CRP concentrations (OR = 0.66, 95% CI = 0.52, 0.84; p
= 0.04) and women had higher odds of elevated CRP compared to men (OR = 2.20; 95% CI = 1.84, 2.63; p
= 0.003). Both current smokers (OR = 1.35; 95% CI = 1.12, 1.62; p
= 0.05) and former smokers (OR = 1.40; 95% CI = 1.16, 1.69; p
= 0.04) had higher odds of elevated CRP concentration compared to those that never smoked.
Despite its inhibitory effect on mineral absorption, phytate possess potent anti-oxidant properties which gives it important therapeutic value. Phytate was shown to be anti-neoplastic and anti-inflammatory in animal and cell culture studies [6
]. This study investigated the relationship between phytate intake and the odds of elevated CRP concentration among participants 20 years and older with overweight or obesity in the NHANES 2009/2010 survey cycle. The median daily phytate intake among subjects was 0.66 g. This is higher than a previously reported value of 0.60 g [25
], primarily due to differences in inclusion/exclusion criteria for the different studies. While the present studies included only adults with overweight or obesity, the previous one included both children and adults and did not exclude subjects with underweight or normal weight status. Phytate intake was higher in men than women, lower in non-Hispanic Blacks and lower in smokers than non-smokers. These findings are consistent with previous studies. For example, Maclean et al. [30
] reported poorer diet quality among smokers compared to nonsmokers and Nielsen et al. [31
] reported higher intake of nuts, a rich source of phytate, among non-Hispanic Whites than both non-Hispanic Blacks and Mexican Americans.
The results of this study indicate that among individuals with overweight or obesity, higher phytate intakes is associated with lower odds of elevated CRP concentration. In obesity, the adipose tissue produces adipokines that induce the production of reactive oxygen species (ROS). The ROS lead to oxidative stress through mechanisms such as fatty acid oxidation [32
], and trigger inflammation. CRP is a non-specific marker of inflammation produced by the hepatocytes in the liver, and its concentration is increased in obesity. Phytic acid may influence the inflammatory process through its anti-oxidant properties. The antioxidant properties of phytic acid are based on its ability to prevent iron-mediated free radical formation, and the suppression of lipid peroxidation [33
]. Da Silva et al. [35
] found that phytic acid treatment in jejunal explants of pigs exposed to fumonisin B1 and deoxynivalenol decreased thiobarbituric acid reactive substances levels and cyclooxygenase 2 expression, and increased levels of the reduced form of glutathione, implying an improvement in oxidative stress markers. In addition, Liu et al. [36
] also showed that phytic acid treatment decreased serum concentration of TNFα, interleukin 6 (IL-6) and IL-1β in male Wistar rats. All these studies support the anti-oxidant/anti-inflammatory function of phytic acid. The findings of this study highlight the importance of dietary phytate intake in reducing the risk of various chronic diseases that are related to CRP concentration such as CVDs and diabetes. CRP has been demonstrated to be predictive of cardiovascular event risk through its interaction with low density lipoprotein and very low density lipoprotein [18
]. Hu et al. have also suggested that CRP may mediate the relationship among other inflammatory markers such as IL-6, and type 2 diabetes [17
Apart from phytate intake, sex and smoking status were found to be associated with the odds of elevated CRP concentration using logistic regression. While the association observed between phytate and CRP is novel, smoking and sex are well-known predictors of CRP concentration. Cigarette smoking results in exposure to reactive oxidant substances that may damage the epithelial cells in the upper airways through peroxidation of cell membranes constituents and induces inflammatory gene activation leading to the secretion of pro-inflammatory cytokines, resulting in inflammation [37
]. The higher odds of elevated CRP among women has also been reported in other studies [38
]. In contrast, Rifai et al. [40
] reported comparable frequency distribution of CRP among apparently healthy men and women in the United States. This was however among individuals within the age range of 40 to 84 years. The discrepancy in CRP between men and women has been attributed, at least in part, to the use of hormone therapy, which has been associated with increased CRP concentration irrespective of type [41
]. The study by Rifai et al. [40
] excluded women taking hormone replacement therapy, thus it was not surprising that they reported comparable CRP distribution between men and women. In the current study, after female hormone use was adjusted for, females still had higher odds for elevated CRP concentration compared to males. This indicates that the higher odds of elevated CRP among women may not be due to hormone replacement therapy alone. Previous studies [39
] have also identified an association between race/ethnicity and CRP concentration, with CRP lower among whites compared to non-white subjects. In this manuscript, although non-Hispanic blacks showed higher odds of elevated CRP concentration compared to non-Hispanic whites in the simple logistic regression (p
= 0.001), this was not statistically significant in the multiple logistic regression (p
= 0.06). In addition, while Ma et al. [43
] have reported a significant association between fiber intake and CRP concentration, dietary fiber intake was not significantly associated with odds of elevated CRP after phytate intake and other factors were adjusted for in the current study. It is worth mentioning that foods high in fiber are also mostly high in phytate, and the inclusion of both dietary factors in the model might be the reason why fiber was not significant. This was done, however, to show that the relationship between phytate and CRP was independent of fiber intake.
The findings of this study have important clinical and public health implications. It is estimated that nearly half of all adults in the United States suffer from one or more chronic disease [44
]. Inflammation plays an important role in the development of several of these chronic diseases [14
]. Dietary modification to include high phytate foods such as nuts, legumes and whole grains may play an important role in efforts to address inflammation and the concomitant adverse health outcome [45
]. Among the limitations for this study are the fact that it is a cross-sectional study, implying that a causal inference cannot be drawn between phytate intake and CRP levels. Additionally, it cannot be determined from this cross-sectional study if prolonged consumption of high phytate foods is sufficient to maintain low inflammation and oxidative stress in obesity, thus warranting future longitudinal studies. Moreover, phytate intake data was estimated using data from another source apart from the NHANES data, although the source is internationally well recognized. In addition, the impact of food preparation on phytate intake was not accounted for in this study. It is also worth mentioning that the findings of this study only apply to individuals with overweight or obesity and not to those with normal or underweight.