Dietary total antioxidant capacity is inversely associated with depression, anxiety and some oxidative stress biomarkers in postmenopausal women: a cross-sectional study

Mental disorders have been associated with a wide range of chronic diseases, disability, and even mortality, particularly among elderly. Depression will be the second leading cause of disease in 2020 as reported by world health organization (WHO) [1]. Postmenopausal women are often at high risk of depression due to the lower level of estrogen [2], as data from longitudinal studies and meta-analyses have noted the chance of developing the depressive symptoms substantially increases during the menopausal transition and early postmenopausal years [3, 4]. Estrogen is involved in mood regulation, and its action is mediated through modulating the receptor binding of serotonin and noradrenaline as well as availability of these neurotransmitters at the synapsis places. So, the decline of estrogen during menopause may underlie depressive mood in menopausal women [5]. Additionally, because of estrogen decline, menopausal women face various distressing symptoms such as hot flashes and sleep disturbance which may increase their vulnerability for mood disorders [6]. Considering the high prevalence of depression (44.2%) and anxiety (67%) among postmenopausal women living in Tehran, Iran [7], finding an approach to modify these symptoms among the women during menopause is of vital importance.

Menopausal women are at high risk for oxidative stress mainly due to estrogen deprivation [8]. Existing evidence suggests that oxidative stress might be linked with development of menopause-associated depression. Estradiol (E₂), a form of estrogen, exerts antioxidant effect through its chemical structure containing the phenolic ring [9]. Besides, E₂ can confer antioxidant activity through modulating the gene expression and function of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase [10]; thereby, reduction in estrogen level may increase the oxidative stress. It was indicated that plasma lipoperoxide (LPO) levels, a marker of oxidative damage, were increased; while total antioxidant status (TAS) and activity of antioxidant enzymes were reduced in postmenopausal women compared with premenopausal women [8, 11].

Diet is considered as the main part of lifestyle modification [12]. For decades, the association between special dietary factors, particularly fruits and vegetables and mental health has been investigated [13]. Although fruits and vegetables have abundant amounts of dietary antioxidants, they cannot adequately represent the overall ability and interactions of antioxidants in the whole diet. Thus, the dietary concept which takes the whole dietary antioxidants into account has become more prominent. Dietary total antioxidant capacity (DTAC) is an indicator of diet quality which is used to estimate the cumulative power of antioxidants in the whole diet [14]. Recently, DTAC is described as an effective tool for determining the health outcomes in middle-aged and elderly populations [15].

To date, DTAC has been associated with various chronic diseases [16‐18], but little attention has been paid to DTAC in relation to mental health. We are aware of a case–control study which showed no significant difference of DTAC between depressed and normal subjects [19]. Examining the relationship between DTAC and mental health is particularly relevant for Middle East countries, where the prevalence of mental disorder is rampant and the quality of life is not desirable. Moreover, concerning the studies that linked the mental disorders to increased risk of illnesses and mortality among the elderly [1], investigating the association between DTAC and mental health in postmenopausal women can be helpful. Given the limited knowledge, we aimed to elucidate the association of DTAC with depression, stress and anxiety and some oxidative stress in postmenopausal women.

The distribution of women in the subscale category of mental health showed that 15% of women had severe and very severe symptoms of anxiety, while this distribution for depression and stress was 7% and 5%, respectively. Furthermore, our data revealed that about 4% of the population study (seven women) had severe and very severe symptoms of all three disorders (data not shown).

As shown in Table 1, with respect to general characteristics, no significant difference was observed across the tertiles of DTAC. The subject at higher tertiles of DTAC had higher dietary supplement use; however, it was not statistically significant (P-trend = 0.08). Women included in the higher tertiles of DTAC had higher median WC than women included in the lower tertile of DTAC (106 vs. 103 cm), although the association was not statistically significant. In addition, subjects in higher tertiles of DTAC were more likely to be physically active (P-trend = 0.02). Although DTAC was not associated with intake of energy, carbohydrate, and protein, but it was inversely associated with fat intake, (P-trend = 0.01), percent of energy from fat (P-trend = 0.003) and positively associated with percent of energy from carbohydrate (P-trend < 0.001). In terms of psychological factors, our data revealed that women at the higher tertiles of DTAC had fewer symptoms of depression and anxiety (P-trend < 0.04).

According to partial correlation adjusted for energy intake, DTAC was highly correlated with the most of the dietary antioxidant components including vitamin C, β-cryptoxanthin, β-carotene, α-tocopherol, lycopene, lutein, zinc, magnesium (P-value < 0.04), but not with selenium. While serum TAC showed no significant correlation with these antioxidants, it indicated a moderate positive correlation with selenium (r = 0.14; P-value = 0.08) (Table 2).

As indicated in Table 3, after controlling for the potential confounders including age, time since menopause, education (year), WC (cm), physical activity (MET-min/week), dietary supplement use (yes/no), dietary intake of fiber (g/day), energy (Kcal/day) and coffee (g/day) in multivariable linear regressions, DTAC was inversely associated with depression (β = − 0.16, P-value = 0.03), anxiety (β = − 0.21, P-value = 0.007), but not stress (β = − 0.10, P-value = 0.1). We ran the same multiple regression for the women with family history of depression (n = 44), and found no significant association between DTAC and depression, stress and anxiety (data not shown).

Multiple linear regression with the same covariates presented in Table 3 showed no association between serum TAC and depression (β = 0.04, P-value = 0.5), stress (β = 0.07, P-value = 0.3) and anxiety score (β = 0.08, P-value = 0.3). MDA level also had no relationship with depression (β = 0.05, P-value = 0.4), stress (β = − 0.008, P-value = 0.9) and anxiety score (β = 0.04, P-value = 0.5). There was no significant association between SOD and depression (β = − 0.03, P-value = 0.6), stress (β = − 0.06, P-value = 0.4) and anxiety (β = − 0.002, P-value = 0.9). Ox-LDL also failed to exhibit any association with depression (β = − 0.03, P-value = 0.6), stress (β = 0.06, P-value = 0.4) and anxiety score (β = 0.03, P-value = 0.6) (data not shown).

Adjusted mean values of serum oxidative stress biomarkers across the tertiles of DTAC are shown in Table 4. There was a significant difference between the adjusted mean of serum level of MDA (P-value < 0.001) and TAC (P-value = 0.04) across the tertiles of DTAC. The lowest adjusted mean MDA was observed at the third tertile of DTAC, while the women at second tertile of DTAC had the highest adjusted mean of serum TAC. No significant relationship was found for ox-LDL and SOD.

Serum MDA showed an inverse correlation with DTAC (Fig. 1), whereas there was no correlation between DTAC and serum TAC, ox-LDL and SOD (data not shown). Multiple linear regression showed that the association between DTAC and serum TAC (β = 0.006, P-value = 0.9), ox-LDL (β = − 0.04, P-value = 0.5) and SOD (β = − 0.13, P-value = 0.07) was insignificant; whereas DTAC was inversely associated with serum MAD level (β = − 0.37, P-value < 0.001) as shown in Table 5.

To the best of our knowledge, the present study is among the few studies investigating the association between DTAC and mental disorders, and is the first study to examine this association among the postmenopausal women. After adjusting for multiple variables, we found an inverse association between DTAC and depression and anxiety scores. However, no association was detected between DTAC and stress score. In respect of oxidative status, serum MDA level was inversely associated with DTAC. Although, there was no linear relationship between serum TAC and DATC, subjects in the second tertile of DTAC had higher serum TAC level compared with the subjects in the first tertile. No association was observed between DTAC and serum ox-LDL and SOD concentration.

In line with our findings, a study on postmenopausal women revealed a strong negative link between the whole plant dietary pattern (consisting of whole grains, fruits, and vegetables) and depression [31]. Several studies also showed that adherence to healthy dietary patterns such as Mediterranean-type diet and Alternative Healthy Eating Index (AHEI) was associated with reduced risk of depression [32, 33] and anxiety [34]. However, a Brazilian study reported no association between DTAC and depression and anxiety [35]. These inconsistencies could be explained by various food processing and cooking in different cultures, which can affect the availability and content of dietary antioxidants [36].

In our study, no significant association was found between DTAC and depression, anxiety and stress in women with family history of depression. This may suggest that high TAC diets may not be as protective in individuals with genetic components of depression as it is in women without family history, although it needs to be confirmed in a larger study.

In the current study, no association was detected between DTAC and stress score. However, the result of other studies reported Mediterranean diet or appropriate consumption of fruits and vegetables (five servings/day) were associated with reduced risk of psychological distress [34, 37]. Further interventions are required to elucidate the effect of DTAC in relation to stress symptoms.

We found that women with higher DTAC had lower serum MDA level. Moreover, participants in the second tertile of DTAC had higher serum TAC level, while the level did not change in the third tertile, suggesting the existence of threshold levels associated with DTAC. However, serum TAC had no association with DTAC in multivariable model. These findings may suggest that high TAC diets may prevent lipid peroxidation, independent of serum TAC in postmenopausal women. So far, studies on the association between DTAC and blood antioxidant status among postmenopausal women and geriatric populations are scare and controversial [38‐40]. A study in overweight and obese postmenopausal women reported that plasma TAC was positively associated with DTAC and dietary intake of antioxidant vitamins such as flavones and proanthocyanidins [38]. Proanthocyanidins and catechins are among the main compounds responsible for the increase of plasma TAC [41]. Notably, tea as the major food source for these compounds [42] was accounted for about 36% of total DTAC estimated in our study, followed by fruit (30%) and vegetable (14%) (data not shown); therefore, consuming more tea and fruits in the subjects with higher DTAC might have resulted in somehow elevated serum TAC and reduced MDA level. However, no association was found between DTAC with plasma TAC, MDA, ox-LDL level and antioxidant enzymes such as SOD in overweight and obese postmenopausal women [40], and elderly subjects [43]. Similarly, consumption of a high TAC diet for 2 weeks did not significantly alter the plasma TAC, ox-LDL, and protein carbonyls compared to low TAC diet in older people, although serum MDA reduced during low TAC diet. The short duration of intervention and compensatory response by homeostatic mechanisms was described for the lack of association [39]. Nevertheless, DTAC was negatively linked with plasma ox-LDL in young adults [30], suggesting that habitual high TAC diet might not be efficient in the substantial modification in ox-LDL in postmenopausal women. These discrepancies could be explained by many factors such as various food processing and cooking which can affect the availability and content of dietary antioxidants, as we mentioned before [36]. In addition, differences in bioavailability or absorption of antioxidants may affect blood TAC level [43]. Furthermore, it is possible that other components of blood antioxidants such as carotenoids may show better association with DTAC [44]. Some experimental studies found no significant increase in TAC level after intake of antioxidant-rich foods, while single carotenoids significantly increased [45, 46]. However, this information was not collected in the present study. Future studies are needed to clarify the effect of DTAC on various blood antioxidants in the menopause age.

The anti-oxidative and anti-inflammatory essence of the antioxidant-rich diets might explain the inverse association between DTAC and depression and anxiety. It is documented that depressive mood is highly related with impaired antioxidant defense and inflammatory status [47, 48]. Additionally, age-related reduction in the level of antioxidants has been shown in the frontal lobe of brain that is vital in mental functions [49, 50].

In our study, serum biomarkers were not associated with psychological factors. Plasma TAC and some other markers of oxidative stress were not associated with anxiety and depression [35]. However, a study in university male students found a negative correlation between serum TAC level and depression score [19]. Measurements of a few oxidative stress biomarkers may not truly reflect the in vivo antioxidant status and investigating various biomarkers has been suggested [51].

The present study has strengths and limitations. First, this study is the first study that explored association between DTAC and mental health in postmenopausal women. Second, to achieve the more accurate DTAC estimation, we assessed the intake of spices and herbs with high TAC value that are frequently used in Iranian diet. The under/overestimation in DTAC assessment due to cultivation procedures, storage, and cooking or some unmeasured confounding factors could have mediated the observed association [36]. Finally, cross-sectional design of study precluded us from concluding any cause–effect relationship.

Our findings suggest that higher DTAC is associated with lower depression and anxiety scores in postmenopausal women. In addition, higher DTAC is associated with lower serum MDA; hence postmenopausal women who are more prone to oxidative stress can reap the benefits of high TAC diets to improve their psychological disturbances and reduce the oxidative damage in their body.