Folate, vitamin B6, and vitamin B12 in relation to diabetes
To say that diabetes is a problem would be a huge understatement. Researchers believe that type 2 diabetes - aka ‘diabesity’ - is a global public health concern currently approaching epidemic proportions.
In the US alone, the prevalence of diabetes has increased significantly over the past few decades. In 2018, 34.2 million Americans were diagnosed: that’s 10.5% of the population.
The percentage of adults with diabetes is increasing with age, reaching 26.8% among those aged 65 years and over.
A 30-year study on adult men and women has suggested that three very important nutrients may play a major role in the development of diabetes: folate, vitamin B6, and vitamin B12.
The Coronary Artery Risk Development in Young Adults (CARDIA) study
The CARDIA study involved a total of 4,704 non-diabetic American adults aged 18–30 years. The adults were enrolled between 1985–1986 and monitored until 2015–2016. A dietary assessment was conducted at the beginning of the study and again in 1992–1993, and in 2005–2006.
In this large prospective cohort study, folate intake (including both dietary and supplemental resources) was inversely associated with the incidence of diabetes among American adults
during a 30-year follow-up.
Over the 30-year follow-up, a total of 655 cases of diabetes occurred among the adults. Analysis of the results showed that these cases were most prevalent among those with a low intake of folate. Adults who took supplements were also found to have higher levels of folate and lower levels of serum C-reactive protein.
Another significant finding was that higher folate intake was also associated with lower plasma homocysteine: a major factor in the onset of diabetes.
The researchers concluded that a low intake of folate in young adulthood could predispose adults to develop diabetes later in life. They also suggested that this finding may be partly related to homocysteine level, insulin sensitivity, and systemic inflammation.
To understand these findings, it’s important to first understand the role that these factors play in diabetes.
Diabetes: prevalence and risk factors
Most of us are aware of the causes of type 2 diabetes. A sedentary lifestyle and being overweight or obese are two of the most common factors, accounting for about 90% to 95% of diabetes cases in the United States.
It’s estimated that more than 1.7 billion adults worldwide are overweight, and 312 million of them are obese. Around 155 million children worldwide are also overweight or obese .
Every year, over 18 million people die from cardiovascular disease, for which diabetes and hypertension are major predisposing factors.
However, other factors are at play.
Another major player in the development of diabetes is hyperhomocysteinemia, a condition caused by abnormally high levels of homocysteine in the blood (above 15 µmol/L). Homocysteine is an amino acid that the body produces through breaking down protein. Elevated homocysteine levels can lead to serious diseases as well as arterial damage and blood clots in your blood vessels.
Previous studies have indicated that high homocysteine levels are often due to a deficiency in vitamin B-12 or folate . Hyperhomocysteinemia has also been linked to insulin resistance .
Elevated homocysteine can occur for a variety of reasons, including genetic defects and renal dysfunction. However, low intake of specific nutrients also play a major role - particularly folate, vitamin B6, and B12.
These B vitamins are crucial for the breakdown and clearance of homocysteine. Folate acts as a prerequisite substrate donor, while vitamins B6 and B12 are essential coenzymes. In addition, these B vitamins are important components of one-carbon metabolism that contributes to DNA methylation, which is also involved in the pathogenesis of diabetes.
Previous clinical trials have shown that folate supplementation can improve insulin resistance and reduce levels of inflammatory mediators . This is a significant benefit in reducing the risk of type 2 diabetes.
The CARDIA study findings
- Participants with higher folate intake were more likely to have higher total energy intake, have better overall dietary quality, be older and males, have a higher education level (in whites), be never smokers (in whites), consume more alcohol, exercise more, have lower BMI, have higher HDL–to–LDL ratio (in whites), and higher TG in blacks, but lower TG in whites.
Additionally, they were less likely to have a family history of diabetes (in blacks) and more likely to use folic acid supplements.
- During 30 years of follow-up, 655 incident cases of diabetes occurred. Folate intake was inversely associated with the incidence of diabetes.
- Regarding the association between intake of vitamin B6 or vitamin B12 and the incidence of diabetes, a significant inverse association was observed only for vitamin B6.
- The associations between B vitamin intakes and diabetes incidence were not significantly modified by age at baseline, sex, race (black vs. white), or fasting glucose at baseline.
- Interestingly, the inverse association between folate intake and diabetes incidence seemed to be more pronounced among older participants and whites. This is possibly because these people consumed more folate in their diet and in supplements.
- When examining the link between folate intake and serum homocysteine, biomarkers of insulin resistance, and systemic inflammation, researchers again found that folate intake was significantly inversely associated with the levels of homocysteine.
- Folate intake was also inversely associated with CRP concentrations among supplement users. C-reactive protein (CRP) is a protein made by the liver. CRP levels in the blood increase when there is a condition causing inflammation somewhere in the body.
Nutritional status and the risk of diabetes
- A low intake of folate is associated with an increased risk of developing type 2 diabetes
- A high intake of folate is associated with a reduced risk of developing type 2 diabetes
- Folate intake was significantly associated with lower levels of Hcy, insulin, and CRP.
Vitamin B6 and B12 in relation to diabetes
Homocysteine and diabetes
The importance of folate
- Decrease hyperglycemia caused by a gestational high-fat and high-sucrose diet in rats
- Reduce insulin resistance in rats with metabolic syndrome
- Significantly decrease circulating insulin and CRP levels in humans
- Reduce oxidative stress, ameliorate endothelial dysfunction, and modulate DNA methylation of genes associated with insulin signaling which may influence the risk of diabetes .
The link between folate intake and homocysteine levels
Reducing the risk of diabetes through diet and supplements
- Swapping refined grains and other processed starches for whole grains
- Reducing or avoiding foods and beverages that contain high amounts of sugar (soda, alcohol, juices, sports drinks). These can be replaced with water, coffee, or tea.
- Increasing intake of healthy omega-3 fats (oily fish, avocado, nuts)
- Limiting intake of red meat and avoiding all processed meats. Replace with lean protein: nuts, beans, whole grains, poultry, or fish.
- Reducing alcohol intake overall. A lower alcohol consumption (up to a drink a day for women, up to two drinks a day for men) increases the efficiency of insulin at getting glucose inside cells.
- Get active. Walking briskly for a half hour every day reduces the risk of developing type 2 diabetes by 30%.