Summary

A study of healthy adults in Greece shows that their consumption of two substances, choline and betaine, are linked to the level of inflammatory markers (e.g. CRP) in the blood; a higher intake is associated with lower inflammatory markers, which themselves are possible precursors of cardiovascular disease.

Introduction

Since the realization that people living in Mediterranean countries had a decreased risk of coronary artery disease compared with northern Europeans and North Americans, the search has been on for the factor or factors responsible. Not surprisingly, nutritional factors have been in the forefront of the search. Recently, the antioxidant resveratrol has become a favorite candidate for a protective effect - news that's been welcomed by wine lovers, although the amounts of the compound in wine are very, very small.

However, other candidates are emerging for the role of leading factor in the Mediterranean diet. Greek researchers have just published a study of dietary choline and betaine intake in the American Journal of Clinical Nutrition. These substances have been reported to affect the homocysteine level, itself a factor for cardiovascular disease. As they are both plentiful in the Mediterranean diet, the researchers decided to examine the links between their intake and the levels of low-grade inflammation in the body.

What was done

The ATTICA study was done on healthy adults between 18 and 89 years old living in the province of Attica, Greece. Over 3,000 inhabitants agreed to participate. They were all interviewed to ascertain their health status, and were given a semi-quantitative food-frequency questionnaire, using pictures to represent different portion sizes. Daily choline and betaine intakes were calculated from food-composition tables.

Fasting blood samples were taken and analyzed for the following inflammatory markers: C-reactive protein (CRP), interleukin-6, homocysteine, and tumor necrosis factor-alpha. In addition, fasting glucose and total cholesterol was determined.

The socio-economic data collected included average income, education levels, smoking status, and physical activity level. Height, weight, and blood pressure were recorded, and the body mass index (BMI) calculated.

For the purpose of analysis, the participants were allocated to three different categories (or tertiles) according to their daily choline intake: less than 250 mg, 250-310 mg, and more than 310 mg daily. Similar tertiles were created for betaine: less than 260 mg, 260-350 mg, and more than 350 mg daily.

What the results showed

There were roughly 1,500 men and 1,500 women making up a total collective of 3,000 people. Their average age was 40; the average BMI was 26 (i.e. slightly overweight, not obese). The major sources of choline in their diets were: beef, potatoes, whole milk, fish, legumes, broccoli, eggs, and poultry. For betaine, the major sources were: spinach, 'vegetable pie', pasta, white bread, pizza, whole-wheat bread, and seafood.

The participants with higher choline levels ate more servings of fruit, vegetables, legumes, and red meat. Those with higher betaine levels were older, more active, and, as for choline, ate more fruit, vegetables, legumes and red meat. Gender, alcohol use, BMI, socioeconomic status, and the presence of diabetes or high blood pressure were not different with different choline or betaine intakes.

The average inflammatory markers levels found in the different tertiles for choline and betaine are given in the tables below:

Markers		Choline Tertiles
	Low	Mid	High
Homocysteine (micromol/L)	11.8	11.5	10.9
CRP (mg/L)	2.30	1.82	1.69*
Interleukin-6 (mg/dL)	1.68	1.40	1.11*
Tumor necrosis factor-a (mg/dL)	6.37	6.35	5.99*

Markers		Betaine Tertiles
	Low	Mid	High
Homocysteine (micromol/L)	12.7	11.5	10.2*
CRP (mg/L)	2.13	1.92	1.61
Interleukin-6 (mg/dL)	1.61	1.44	1.42
Tumor necrosis factor-a (mg/dL)	6.80	6.00	5.99*

* = significant difference between low and high values

It can be seen that participants who ate higher choline amounts had, on average, 22% lower CRP levels, 26% lower interleukin-6 levels, and 6% lower tumor necrosis factor-alpha levels, compared with those who ate least choline. Similarly, higher betaine consumption was associated with 10% less homocysteine, 19% less CRP, and 12% less tumor necrosis factor-alpha in the blood.

When subgroups were formed that combined the choline and betaine intakes, it was found that a high intake of both choline and betaine was linked to lower concentrations of all the investigated inflammatory markers.

What these findings may mean

This study shows an association between choline and betaine intakes and the inflammation process in healthy Greek adults, who presumably consumed a Mediterranean-type diet. The authors of the study point out that, whatever the mechanism underlying the findings, the magnitude of the differences between the inflammatory markers in the low and high tertiles is similar to those found in subjects following the Mediterranean diet.

These inflammatory markers are believed to be important factors in the initiation of cardiovascular disease. It's possible that they represent the path whereby the Mediterranean diet is successful in warding off such disease. The next step (apart from confirming these results) will be to see if there are beneficial clinical effects of prolonged consumption of choline and betaine supplements.

In the USA, the average choline intake is similar to that in Greece. But the average betaine intake in Greece is substantially higher than that in the USA. Betaine is usually found in plants, and the native Greeks tend to eat more vegetables and fruits than Americans. Maybe this is enough to nudge people towards a more vegetarian diet . . .