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Daily folate consumption may be beneficial in reducing all-cause and cardiovascular disease mortality, study finds

In a recent study published in the Nutrition Research Journal, researchers explored the association between daily folate intake, cardiovascular disease (CVD), and all-cause mortality.

Study: Daily Folate Consumption Is Associated with Reduced All-Cause and Cardiovascular Disease Mortality Among US Adults with Diabetes, Prediabetes, or Insulin Resistance. Image Credit: luchschenF/


Research suggests that folate may be a modifiable factor in diabetes prevention. Folate consumption from foods or supplements also prevents CVD in the general population.

While some previous studies have demonstrated a potentially beneficial influence of folate for comparatively healthy individuals, research is needed to assess the particular impact of folate on dysglycemia-related mortality.

About the study

In the present study, researchers hypothesized that the consumption of folate daily may have a protective effect on mortality in dysglycemia patients.

The National Health and Nutrition Examination Survey (NHANES) is a complex, multistage probability survey that monitors United States citizens' nutritional and health status. The team calculated daily folate consumption by adding the daily folate intake from food and daily folate supplements.

Trained interviewers collected data on folate intake from foods through a 24-hour diet recall. Each participant had access to a set of measuring instruments in the NHANES Mobile Examination Center (MEC) dietary interview room for recording the quantities of all foods consumed in the previous 24 hours.

Administrative information, such as data dependability and completeness, was recorded to ensure data quality. The US Department of Agriculture's Food and Nutrient Database for Dietary Studies estimated the daily folate intake from food. The average daily folate intake was also estimated to reduce potential measurement errors related to a 24-hour recall.


Participants with prediabetes, diabetes, and insulin resistance (IR) were followed for 158,129, 117,746, and 2,10,896.80 person-years, respectively. Among these, 3,356 (1,053 CVD and 672 cancer), 3,796 (1,117 CVD and 854 cancer), and 4,340 (1,286 CVD and 928 cancer) deaths occurred among these participants with diabetes, prediabetes, and IR, respectively.

Almost 21% of participants with diabetes met the estimated average daily requirement for folate, and 29.42% consumed folate supplements. Furthermore, 27.17% of prediabetes participants consumed folate daily, and 24.14% consumed folate supplements. Also, 29.75% of participants with IR consumed folate daily, and 20.32% took folate supplements.

All participants' daily folate consumption was substantially and inversely related to glycated hemoglobin A1c (HbA1c), fasting plasma insulin (FPI), and homeostasis model assessment of insulin resistance (HOMA-IR) on a dose-response basis.

Higher daily folate intake was also substantially and dose-dependently correlated with lower fasting plasma glucose (FPG) and C-reactive protein (CRP) in prediabetes or diabetes patients but with increased thyroxine in those having IR or diabetes.

Elevated daily folate intake was remarkably associated with higher total triglyceride and cholesterol levels in participants with insulin resistance and elevated high-density lipoprotein (HDL) levels in those with diabetes.

In all multivariate models, a considerable inverse correlation existed between daily folate intake and all-cause mortality, cardiovascular disease, and cancer among prediabetes or diabetes patients. In participants having diabetes, a one-unit rise in ln-transformed folate intake was remarkably related to a 7.1% reduction in all-cause, an 11.4% decrease in CVD, and a 6.4% reduction in cancer mortality.

Also, in prediabetes patients, each one-unit rise in ln-transformed folate intake was associated with a 3.6% reduction in all-cause, an 7.8% decrease in CVD, and a 3.6% reduction in cancer mortality.

Among IR patients, daily folate intake was inversely connected to all-cause and CVD mortality in continuous and categorical models, whereas there was no significant relationship between folate consumption and cancer mortality.

In the restricted cubic spline model, the HR of CVD, all-cause, and cancer mortality was considerably and linearly decreased with increasing daily folate intake among all participants.

In diabetes, prediabetes, or IR patients, dietary folate intake was significantly associated with mortality from CVD, all causes, and cancer.

Participants who consumed folate supplements reported notably lower all-cause and CVD mortality among those having diabetes, significantly lower cancer and all-cause mortality among prediabetes patients, and lower all-cause mortality among insulin-resistant patients.

Among diabetes patients, diabetes duration notably modified the association between daily folate intake and CVD, cancer, and all-cause mortality, and the association was only significant among 14 participants with diabetes duration of less than ten years.


The study findings showed among diabetes, prediabetes, or IR, an increase in daily folate intake may reduce the risk of mortality, particularly mortality from CVD.

These findings suggest that persons with dysglycemia may benefit significantly from folate consumption. Additional research is required to validate the present findings and elucidate the possible mechanisms.

Journal reference:
  • Liu, W. et al. (2023) "Daily Folate Consumption Is Associated with Reduced All-Cause and Cardiovascular Disease Mortality Among US Adults with Diabetes, Prediabetes, or Insulin Resistance", Nutrition Research. doi: 10.1016/j.nutres.2023.04.007.

Posted in: Medical Science News | Medical Research News | Medical Condition News | Healthcare News

Tags: Agriculture, Cancer, Cardiovascular Disease, Cholesterol, C-Reactive Protein, Diabetes, Diet, Fasting, Food, Glucose, Glycated hemoglobin, HbA1c, Hemoglobin, Insulin, Insulin Resistance, Lipoprotein, Mortality, Nutrition, Prediabetes, Protein, Research, Supplements, Triglyceride

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Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.

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