Introduction

Multimorbidity can be defined as the simultaneous occurrence of at least two diseases in the same person, and it can be a combination of several different chronic diseases1. The coexistence of multiple diseases complicates the management of this group of patients, with more comprehensive treatment needs leading to greater consumption of health resources, and prevention and improved management of multimorbidity are now key priorities in many countries2. Cardiometabolic multimorbidity (CMM), defined as the coexistence of 2 or more cardiometabolic diseases (CMD), including hypertension, diabetes, stroke and cardiovascular disease, is one of the most common multimorbidity patterns3. The incidence of CMM has significantly increased over the past two decades with the rise in life expectancy and ongoing advancements in the management of cardiovascular diseases and diabetes4. In addition, developing one CMD greatly increases the risk of developing another5, and each additional CMD, in any combination, carries an exponential mortality rate6. In low- and middle-income countries, these disincentives can place a heavy burden on individuals, families and health-care systems due to the vulnerability of social protection and health systems7,8.

There has long been solid evidence comprehensively evaluating diet in relation to CMD, but a limited number of studies have directly examined the association between diet and CMM. In a study of a Canadian cohort of 13,226,748 cases, it was noted that after controlling for confounding variables, there was no significant difference in the consumption of daily dietary intake in the CMM cohort compared to the no-CMD group9. However, Yunanjie Zheng et al. showed that men (OR 1.20, 95% CI 1.04–1.39) and women (OR 1.55, 95% CI 1.29–1.85) with high-risk dietary intake had a higher risk of CMM than subjects without high-risk dietary intake8. Notably, a significant association between diet and first CMD (FCMD), but no significant correlation between and CMM onset was observed in the Archana Singh-Manoux mean 23-year survey10. Yuting Han reached similar conclusions in a cohort study involving 500,000 Chinese adults11. This evidence also points to the differential impact of a risk factor on the progression from health to FCMD, CMM, and death, as well as on the disease-specific transition10,11. Few of these studies of diet and CMM have considered the relationship between single nutrients and CMM.

Vitamin A, a nutrient with antioxidant properties, has been of great interest for its beneficial effects on CMD. The association between carotenoids from plants (e.g., fruits and vegetables, etc.) and dietary intake of retinol as well as total vitamin A from animals (liver, kidneys, dairy products, etc.) and the risk of CMD was confirmed in recent studies12. In a prospective study focusing on hypertension, it was pointed out that the total dietary intake of vitamin A showed an L-shaped relationship with the incidence of new-onset hypertension13. Subsequently, in a study involving 17,111 participants with a median follow-up time of 11 years, the authors reported an inverse relationship between dietary intake of vitamin A and the risk of diabetes, particularly in men (HR 0.69, 95% CI 0.49–0.97)14. A meta-analysis pooling the combined effects of 20 observational studies of risk indicators showed that vitamin A and its organic compounds were negatively associated with the risk of stroke (log OR − 0.46, 95% CI − 0.81; − 0.12)15. Thus far, most of the widely reported associations have focused on a single disease pattern; it is inappropriate to directly hypothesize an association between vitamin A and the risk of CMM, and there are no studies that have demonstrated the applicability of this relationship to populations with CMD.

Therefore, in order to fill the gaps in existing knowledge, we will use the data from the China Health and Nutrition Survey (CHNS), a longitudinal study spanning 18 years, to comprehensively investigate the prospective association between dietary total vitamin A, β-carotene, retinol intake, and CMM, providing important epidemiological evidence for the prevention of CMM at the level of knowledge.

Methods

Study population

The CHNS is an ongoing multipurpose longitudinal study that began in 1989–2015 and includes 288 communities in 12 provinces/autonomous municipalities in China, with follow-up visits scheduled every 2 to 4 years. According to the 2010 census, the provinces included in the CHNS sample accounted for 47% of China’s population by 2011. The CHNS was established as a joint project of the University of North Carolina at Chapel and the Chinese Academy of Preventive Medicine (now the China Center for Disease Control and Prevention [CCDC]). Each round of surveys collected data on sociodemographic factors, diet, physical activity, health and behavioral changes at the household and individual level in relation to urbanization and social and economic changes at the community level16. A detailed description of the methodology of the survey and design is presented in other literature17,18,19.

This study used data from 1997 to 2015 and included a total of 22,545 subjects who participated in at least 2 surveys. We excluded those aged < 18 years (N = 6481), without intake or demographic information (N = 425), without information on CMM diagnosis (N = 1049), abnormal energy intake (< 800 or > 6000 kcal/days for males and < 600 or > 4000 kcal/days for females) (N = 344), females who were pregnant or breastfeeding (N = 299), and baseline those who had CMM (N = 344). Finally, a total of 13,603 participants were included in the study (Fig. 1).

Figure 1
figure 1

Flowchart of participant selection from the China Health and Nutrition Survey (CHNS) 1997–2015.

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Assessment of nutrient intake

In each survey, dietary assessment is conducted face-to-face by trained nutritionists. Individual dietary data are collected using standardized questionnaires, with a 24-h dietary recall conducted on each of three consecutive days randomly assigned each week. Meanwhile, a combination of weighing and measurement techniques is used to measure household food consumption based on stock changes from the beginning to the end of each day, with dietary intake expressed as per capita daily consumption. The consumption of cooking oil and seasonings by each individual in the household is estimated through weighted household food intake. Previous detailed descriptions of dietary measurements have been published, and the accuracy of dietary assessment methods has been validated20,21.

The total dietary intake for each subject was obtained by summing the individual dietary review data with the consumption intake of edible oils and condiments from the household food stock22. Nutrients were assessed by multiplying the nutrient content of each food item by a standardized portion size and totaling it with the dietary intake according to the China Food Composition Table (CFCT)23. In view of the fact that it is often necessary to test for different forms of vitamin A in food and that each form has its own different biological activity, the biological activity of vitamin A is generally expressed in terms of retinol equivalents(RE)23,24. Supplemental intake of dietary vitamin A is not included in the total dietary vitamin A intake. The intake of each nutrient is represented by calculating the cumulative average value from the baseline to the last available round before the final round.

Covariates

In our current study, the covariates selected were factors known or suspected to be associated with the risk of CMM or variables that differed significantly between different sources of vitamin A intake, which were obtained in a structured questionnaire, including age, sex (male/female), district (rural/urban), region (north/south), education (Illiteracy/Primary school/Middle school /High school or above), smoking status (Current smoker/Former/Never), alcohol drinking (no/yes), individual income level (Low/Medium/High/Very high), body mass index (< 18.5/18.5–24/24–28/ ≤ 28, BMI), physical activity (light/moderate/heavy/unknown), and dietary intakes of total energy, protein, carbohydrate, dietary fiber, sodium to potassium ratio, calcium, zinc, vegetables, fruits.

Assessment of CMM

The main outcome was CMM, defined as progression to at least two of the following cardiometabolic diseases: hypertension, diabetes, stroke and myocardial infarction. The participant's disease history was synthesized by responses to the following questions at each follow-up visit: “What was the doctor’s diagnosis of your illness or injury?” “Has a doctor ever told you that you suffer from high blood pressure/diabetes/myocardial infarction/stroke?” “How old were you when the first event occurred?” “Has the event happened in the past year?” “Did you use any of these treatment methods?” “Are you currently taking anti-hypertension drugs?” Among the diagnosis of hypertension are two additional criteria: (1) an average of 3 systolic BP (SBP) measurements ≥ 140 mmHg; (2) an average of 3 diastolic BP (DBP) measurements ≥ 90 mmHg. Blood samples were only available for collection and assay in 2009, so in 2009 we added fasting glucose ≥ 7.0 mmol/L or HbA1c ≥ 6.5% (48 mmol/mol) to the criteria for a diagnosis of diabetes25.

Statistical analysis

The follow-up time is calculated from the start of participants’ involvement in the survey to the diagnosis by CMM, death, or the end of follow-up in these three states, whichever comes first. In all subsequent analyses, participants were divided into five groups according to the quintiles (Q1–Q5) of total vitamin A intake. Continuous variables in baseline characteristics were summarized as mean and standard deviation (SD) or median (IQR), categorical variables were expressed as frequency and percentage, and differences between different quintiles of vitamin A intake were compared using ANOVA tests or Chi-square tests.

To assess the relationship between total intake of vitamin A, β-carotene, and retinol in the diet and the risk of CMM, three multivariate Cox proportional hazards regression models were established. Model 1 was unadjusted. Model 2 was adjusted for age, sex, regions, district, education, and Model 3 was adjusted for age, sex, regions, district, education, smoking, alcohol, income, BMI classification, physical activity, total energy, total protein, total carbohydrates, total dietary fiber, sodium to potassium intake ratio, calcium, zinc, vegetables, fruits intake. To assess possible differences between vitamin A intake in patients with specific CMDs and those with CMM, we also analyzed patients with hypertension, diabetes mellitus, cardiovascular disease, and stroke separately using Model 3. Missing covariates were imputed using the MICE package in R Studio 4.2.3 software26, employing the Predictive Mean Matching (PMM) imputation method with five iterations to generate datasets for education (0.9%), individual income level (4.8%), body mass index (0.3%), and physical activity (0.3%). The linear trends were tested by assigning a median value to each quintile of the vitamin A intake. Moreover, the dose–response associations of dietary total vitamin A, β-carotene, retinol intake and the risk of CMM were examined using restricted cubic spline regression with five knots (Three knots were used in retinol intake and the risk of CMM), adjusted for the confounding variables mentioned above.

In addition, to explore the relationship between vitamin A intake and the risk of CMM among specific populations, we also performed stratified analyses based on BMI (< 24, ≥ 24), age (≤ 45, 46–60, ≥ 61), sex (male/female), and CMM subcategories. We tested for potential effect modification using interaction models. The potential effect modification was examined using the interaction models. In addition, we excluded participants who developed CMM during the first 2 years of follow-up to perform an assessment of the robustness of the results. All analyses were performed using R (version 4.3.2). All statistical tests were two-tailed and considered significant at p < 0.05.

Results

Characteristics of study participants

This study included a total of 13,603 participants, consisting of 6534 males (48.0%) and 7069 females (52.0%). The mean baseline age of the participants was 43.9 (SD 14.8). The median dietary intake of total vitamin A, β-carotene, and retinol is 530.5 (301.0, 998.2), 2602.0 (1418.8, 4730.4), and 110.4 (44.1, 288.7) μg RE/day. Table 1 shows the main baseline characteristics of participants in the vitamin A intake quintile group. Compared to the first group, participants in the highest intake group were more likely to reside in the northern region, have a higher proportion of urban residents, possess higher levels of education and income, and have a higher likelihood of alcohol consumption. In terms of dietary intake, the intake of all increased in the quintile groups, while the ratio of sodium to potassium intake showed a decreasing trend.

Table 1 Baseline characteristics of the study population according to Vitamin A intake quintiles and cumulative mean nutrient intake.
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Associations between vitamin A intake and cardiometabolic multimorbidity

During a median follow-up period of 9.0 years, we ascertained 1050 incident cases of CMM. Table 2 shows the association between vitamin A intake and CMM risk. After adjusting for all covariates, the multivariate-adjusted HRs and 95% CIs from lowest to highest vitamin A intake were1.00 (ref), 0.60 (0.48–0.74), 0.82 (0.67–1.00), 0.65 (0.53–0.80) and 0.76 (0.61–0.96), revealing a negative association, with the lowest risk of CMM in the Q2 group (254.35–432.57 μg RE/day), but the p-trend value (0.419) showed a non-significant linear trend. Therefore, we further analyzed the nonlinear relationship based on Model 3 by setting intake as a continuous variable and using restricted cubic spline. In Fig. 2A, the association between vitamin A intake and CMM risk appeared to be U-shaped, but not significantly (p non-linear 0.132). The U-shaped curve showed that vitamin A intake was not protective when it exceeded 1427.40 μg RE/day. For patients with specific CMD, the risk of CMM was reduced in patients with hypertension, cardiovascular disease, stroke, and diabetes when vitamin A intake was ≥ 254.35 μg RAE/day. Their HRs and 95% CIs compared with the lower intake group were 0.74 (0.63–0.88), 0.68 (0.49–0.95), 0.73 (0.60–0.88) and 0.75 (0.61–0.93) (Table 3).

Table 2 The relationship between cumulative mean intake of vitamin A, β-carotene and retinol and cardiometabolic multimorbidity risk.
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Figure 2
figure 2

Cubic spline curves for the associations between intakes of total vitamin A (A), β-carotene (B) and retinol (C) with CMM risk. HR (95% CI) was based on a mixed-effects Cox proportional hazards model adjusted for age, sex, region, area, education, smoking, alcohol consumption, income, BMI classification, physical activity, total energy, total protein, total carbohydrates, total dietary fiber, sodium-to-potassium intake ratio, calcium, zinc, vegetables, fruits intake. Histogram showing the distribution of intake of vitamin A, β-carotene, and retinol.

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Table 3 The relationship between cumulative mean intake of vitamin A, β-carotene and retinol and CMM risk in patients with specific CMD.
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Association between β-carotene intake and cardiometabolic multimorbidity

A similar relationship was found in β-carotene Intake. When using the first quintile (Q1) as reference, the multivariable-adjusted HRs (95% CI) of Q2 to Q5 for CMM risk were 0.63 (0.51–0.78), 0.79 (0.65–0.97), 0.66 (0.54–0.82) and 0.77 (0.62–0.97), respectively, p for trend 0.430 (Table 2). When β-carotene intake was in the range of 1186.27–2090.85 μg/day (Q2), the risk of CMM was reduced by 37% compared with the lowest intake group (Q1 < 1186.27 μg/day). We used a restricted cubic spline method to construct a visual model, confirming the U-shaped relationship between β-carotene intake and the risk of CMM, but not significantly (p non-linear 0.289, Fig. 2B). At lower intake levels, β-carotene intake showed an inverse correlation with the risk of CMM, and the protective effect against CMM was lost when the intake exceeded 4375.81 μg/day. The protective effect of β-carotene on the risk of CMM was also observed at lower intake levels. For CMD patients with β-carotene intake ≥ 1186.27 μg/day, β-carotene was inversely associated with CMM, with HRs and 95% CIs values of 0.75 (0.63–0.88), 0.69 (0.49–0.97), 0.70 (0.57–0.84) and 0.70 (0.56–0.87) in patients with hypertension, cardiovascular disease, stroke and diabetes (Table 3).

Associations between retinol intake and cardiometabolic multimorbidity

In the analysis of retinol intake, the risk of CMM was consistently lower in Q2–Q5 than in Q1 in all models. Fully adjusted HRs (95% CI) were 0.70 (0.57–0.86), 0.67 (0.55–0.82), 0.68 (0.55–0.83), and 0.60 (0.49–0.74) respectively, p for trend 0.002 (Table 2). Compared with the lowest quintile, the highest quintile had a 40% decreased risk of CMM. Spline models with fully adjusted covariates were constructed to profile a more direct relationship between retinol intake and cardiometabolic multimorbidity. As depicted in Fig. 2C, the results of multivariate Cox regression with restricted cubic spline (3 knots) found an L-shaped relationship (p non-linear < 0.001). As retinol intake increased, the risk of developing CMM tended to decrease, but eventually leveled off. In all patients with specific CMD, we found that retinol intake had a reducing effect on the risk of CMM (Table 3). The HRs and 95% CIs were 0.68 (0.58–0.80), 0.56 (0.40–0.79), 0.60 (0.42–0.84), 0.60 (0.49–0.73) in patients with hypertension,cardiovascular disease, stroke and patients with diabetes mellitus, respectively (Table 3). Similarly, it was also among cardiovascular disease patients that the risk of CMM fell the lowest.

Subgroup analysis

To further explore potential influences on the relationship between vitamin A intake and CMM, we analyzed the results by BMI, age, gender, and CMM cohort were stratified. In Fig. 3 we observed that among participants with relatively high levels of raw vitamin A, β-carotene, and retinol (BMI ≥ 24 kg/m2 supergroup, female group, and middle-aged group aged 46–60 years), the risk of CMM was lower compared to the other groups. Even apart from age, no significant interactions were found between vitamin A, β-carotene, retinol and these other stratification variables (p for interaction > 0.05).

Figure 3
figure 3

Subgroup analysis for the association between vitamin A, β-carotene and retinol and CMM risk. 1HR (95% CI) was based on a mixed-effects Cox proportional hazards model adjusted for age, sex, region, area, education, smoking, alcohol consumption, income, BMI classification, physical activity, total energy, total protein, total carbohydrates, total dietary fiber, sodium-to-potassium intake ratio, calcium, zinc, vegetables, fruits intake. 2CMM cardiometabolic multimorbidity, HR hazard ratio, CI confidence interval.

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Supplementary Figure 1 shows the different groups of CMM. Among all participants, the top 5 groups were hypertension and diabetes (4.04% of the total population), hypertension and cardiovascular disease (1.24% of the total population), hypertension and stroke (1.13% of the total population), hypertension, diabetes, and cardiovascular disease (0.54% of the total population), and hypertension, diabetes, stroke (0.35% of the total population). There still exists an association between vitamin A and different combinations of CMM, although not significant in some categories. Vitamin A, β-carotene and Retinol intake present a stronger protective effect in the combination of hypertension and stroke (Supplementary Table 1). In order to minimize reverse causality as much as possible, after excluding patients who developed CMM during the first two years of follow-up, the analysis results were consistent with the main analysis results (Supplementary Table 2).

Discussion

This study is grounded in a national population-based prospective cohort, utilizing information from 1997 to 2015, involving 13,603 subjects. To the best of our knowledge, this is the first study to report the association between different sources of vitamin A in the diet and CMM as well as different CMM clusters, and therefore we are unable to make direct comparisons with the available evidence. We observed that both total dietary vitamin A, β-carotene and retinol intake, were significantly negatively associated with the risk of CMM in female and in individuals with BMI ≥ 24 kg/m2. There was an L-shaped association with a ceiling effect between retinol intake and the risk of CMM, with the risk of CMM showing a decreasing trend as retinol intake increased, but eventually leveling off. In specific CMD populations, the protective effect of dietary vitamin A intake on CMM was stronger in the cardiovascular patient population, both for β-carotene intake and retinol intake. Further analyses showed that relatively low intakes of vitamin A, β-carotene, and retinol were associated with a lower risk of CMM in the overweight, middle-aged and female groups. Furthermore, consistent with previous studies27, the most common CMM cohort in our study was hypertension and diabetes (4.04%), and there was an association between intake of vitamin A, β-carotene, and Retinol and different CMM subtypes, with the combination of hypertension and stroke being the most significant.

Even though there is no way for us to mirror the existing evidence, our results are consistent with the study of CMD risk outcomes. Research on the cardiometabolic effects of diets with high antioxidant capacity has been in the spotlight to date, and previous studies have reported extensively on the effects of vitamin A on cardiometabolic health at the level of serum concentrations, supplements, and dietary intake. According to previous reports, many studies have yielded results that increased intake of vitamin A is strongly associated with a reduced risk of hypertension28,29,30, diabetes31, cardiovascular disease32,33, and stroke15, and that vitamin A has beneficial cardiovascular effects by attenuating lipid peroxidation and free radical-induced damage34. Chi-Ho Lee utilized data from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS), which reported that dietary intake of vitamin A was independently and negatively associated with the occurrence of adverse cardiovascular outcomes at a median follow-up of 22 years (HR 0.68, 95% CI 0.53–0.88)35. A prospective cohort that systematically evaluated the relationship between 29 nutrients and CVD reported that dietary vitamin A intake was significantly negatively associated with CVD (HR 0.70, 95% CI 0.54–0.91)36. In our study it was similarly shown that when daily intake of vitamin A through the diet was effective in reducing the risk of CMM by 40%, the protective effect was more pronounced in patients with cardiovascular disease than in patients with other types of CMD in the diseased population. This suggests that vitamin A intake is equally important both in the prevention of first-time CMD disease and in the transition from CMD to CMM.

Carotenoids, as the main components of vitamin A, not only possess the highest vitamin A activity37, but blood concentrations of carotenoids are also considered biomarkers of fruit and vegetable intake38,39, making them a focal point in research. There have been many studies exploring the association between carotenoids and cardiac metabolism40,41. A meta-analysis of 69 prospective studies showed a non-linear relationship between total dietary carotenoid intake and cardiovascular disease (p non-linearity = 0.002), with most risk reductions ranging from 4000 to 6000 μg/day42. Yi-Wen Jiang found an association between high dietary β-carotene intake and low risk of type 2 diabetes mellitus in 77,643 subjects from the West by integrating the results of six cohort studies (RR 0.78, 95% CI 0.70–0.87)43. A meta-analysis of stroke also reported that increased levels of β-carotene were more effective in reducing stroke risk at higher ages (log OR − 0.61, 95% CI − 1.09; − 0.12)15. This corroborates with the observation of a negative association between dietary intake of β-carotene and CMM in our current study. Also, in a specific CMD population, we found a protective effect of β-carotene intake against CMM. Serum carotenoid levels in humans can be representative of average daily intake, and a prospective study found that higher serum carotenoid concentrations were associated with a lower risk of all-cause and cardiovascular mortality in hypertensive adults44. Carotenoids have been shown to reduce reactive oxygen species-induced damage, prevent lipid peroxidation, and participate in cellular communication that regulates proliferation and apoptosis45,46,47. It is able to fuel the immune system to function more effectively by protecting cells and tissues from damage caused by free radicals and mono-linear oxygen species48.

Compared to vitamin A and carotenoids, the available data suggest that relatively little research has been done on retinol. Yaren Yu designed a nested case–control study to assess the effect of plasma retinol on the risk of first stroke, and plasma retinol was significantly and inversely associated with the risk of first stroke (OR 0.92, 95% CI 0.86–0.97)49. Yuanyuan Zhang’s 11-year longitudinal study of 12,245 adults had an adjusted multivariate risk ratio of 0.76 (95% CI 0.70–0.82) for the risk of new-onset hypertension compared with the group with the lowest dietary intake of retinol13. These results have been confirmed in case–control and longitudinal studies assessing the risk of coronary cardiovascular disease50,51, but there was a 1.4-fold (95% CI 1.2–1.8) increased risk of CVD death when plasma retinol concentrations varied outside of the clinical reference range (1.05–2.80 μmol/L)52. Consistent with the above studies, dietary retinol intake was found to reduce the risk of CMM in our study, with the difference that when retinol intake was explored as a continuous variable for a nonlinear relationship, the relationship found presented a significant L-shaped result. Notably, Lei Su followed 8534 men and 8577 women in China and also found that there was a ceiling effect on the protective effect of retinol intake against diabetes in the male population14. In summary, although the results of the current study suggest that having a higher level of dietary intake of retinol may be beneficial in terms of risk compared to patients with a lower dietary intake of retinol, there is a limit to its usefulness. The intake of retinol, which is mostly derived from animal foods, should be considered in the context of adverse health outcomes53.

Notably, in all populations, we also observed a positive association between vitamin A and β-carotene and the risk of CMM after threshold intake, and previous studies on carotenoids and CMD have found similar associations. In a prospective study by Zixin Qiu, investigating 3107 patients with type 2 diabetes mellitus (T2D), it was found that β-carotene may show pro-oxidant effects under certain conditions, and that higher serum concentrations of β-carotene, as compared with those of other carotenoids, were significantly associated with an increased risk of cardiovascular death in patients with T2D during an average follow-up of 14 years54. Jiaqi Yang, in their meta-analysis that included 10 trials and 16 reports, showed that a slightly increased cardiovascular morbidity was observed when β-carotene supplementation was given alone (RR 1.04 , 95% CI 1.00–1.08)55. Excessive intake of β-carotene promotes peroxidation in vivo, especially in tocopherol alpha-deficient diets, as the presence of other antioxidants in the body may attenuate the pro-oxidant effects of β-carotene56,57,58. To date, consideration of the specific effects of β-carotene intake has been lacking, although both China and the United States have set a tolerable upper intake level (UL) of 3000 μg/day for vitamin A in adults59,60. As can be seen in our results, the threshold for vitamin A intake was < 1427.40 μg RE/day, while the threshold for β-carotene was < 4375.81 μg/day. However, since the p non-linear results are not significant, and UL may be influenced by the nutritional status and cardiovascular risk of the population at baseline55, the interpretation of this result we should be more cautious. In addition, both retinol and carotenoids are major sources of vitamin A intake. However, in our current study, the average intakes of carotenoids and retinol were 4320.74 μg/day and 343.15 μg/day, respectively, and the source of vitamin A was mainly a plant-based diet, and retinol accounted for only 36.52% of the total vitamin A intake (RAE), and the intake of retinol was similar to that of the previous study, which was much lower than that of European countries (835 μg/day)61. A more comprehensive and in-depth study of optimal retinol intake should be conducted when dietary structure changes.

The influence between BMI, age and gender and the protective effect of vitamin A was also emphasized in our study. In the middle-aged (46–60) group, vitamin A was more effective in reducing the risk of CMM. This finding is consistent with the findings of Sajjad Farashi, who noted in his article that the negative correlation between older age and higher levels of β-carotene, retinol and vitamin A and the risk of stroke was stronger (Rho =  − 0.51, p < 0.05)15. And the finding that higher intake of vitamin A is more beneficial for the female population is also the same as Lei Su’s findings on diabetes14. In animal experiments, it has been found that the bioavailability and conversion efficiency of vitamin A in rats are significantly affected by sex, with higher bioavailability in females compared to males, and that Vitamin A metabolism in females is also hormonally mediated62, with estradiol increasing retinoic acid receptor alpha gene expression63. In addition, women retain much more vitamin A in the liver than men do, regardless of its source64, so the differences in the role of dietary vitamin A between men and women may be related to the distribution and expression of its associated receptors14. The presence of lower serum carotenoid concentrations in the obese group may contribute to a better mobilization of these antioxidants65,66, showing a better risk reduction compared to the group with a lower BMI. Base on CFCT, the recommended Nutrient Intake (RNI) of vitamin A were 800 and 700 mg RE/day, respectively, for males and females, and only 34.90% of the participants in our study met the standard. In conclusion, our opinion is in line with other studies that vitamin A intake needs to be further enhanced in Chinese populations, especially in women and middle-aged and older adults67, and that dietary improvement and increased intake of retinol are also needed to enhance the primary prevention of CMM.

Although our study used a large sample for a longer-term longitudinal study to explore the association between different sources of dietary vitamin A and different subtypes of CMM separately, there are still several non-negligible limitations. First, with regard to the determination of outcomes, most outcomes are self-reported and therefore may be subject to memory bias. In our median 9.0-year study, the prevalence of CMM was 7.71%. Evidence suggests that the prevalence of CMM in the general population of China increased from 2.41 (95% CI 2.38–2.44%) to 5.94% (95% CI 5.90–5.99%) between 2010 and 201668. Second, vitamin A-related serum concentrations were lacking in the survey, and there was no way to compare differences between dietary intake and serum concentration levels in the analyses. Third, the database for assessing nutrient intake was derived from the China Food Composition Table (CFCT), which lacks complete information on other carotenoids, possibly leading to an overestimation of β-carotene intake. Fourth, even after adjusting for confounding factors, the influence of other potential factors still could not be excluded. Fifth, we had no access to information on the use of dietary supplements and could not tell whether there would be an effect on the results. However, in a study on the use of nutritional supplements in the Chinese population, which included a nationally representative sample, it was noted that the use of nutritional supplements is low among the Chinese population69. Sixth, there were relatively few cases of stroke and cardiovascular disease during the follow-up period, which limited our ability to examine associations between different disease states and transitions. Seventh, because the study was conducted in China, there are large differences between the study and Western dietary patterns, which may affect the generalization of the results.

Conclusions

Our study demonstrated a negative association between dietary intake of vitamin A, β-carotene, and retinol and CMM risk, and this protective effect was more pronounced in patients with cardiovascular disease. There was an L-shaped association between retinol intake and CMM risk. Our findings highlight the need for further adequate dietary intake of vitamin A to enhance primary prevention of CMM, especially in the middle-aged and elderly, overweight and female populations.