Choline Nutrition

Question 1

Choline structure and properties

Answer 1

alcohol with nitrogen and 3 methyl groups around the nitrogen
* water soluble - can be consumed to lipid form
* lipid soluble - head group can be cleaved

Question 2

What is the main form in which choline is found?

Answer 2

Phosphatidylcholine lipid

Question 3

Roles of choline

Answer 3

• Signalling molecule: Lysophosphatidylcholine is precursor that tell immune system to work
• Methyl group donor: Betaine is a breakdown product and similar role to folate
• Bile Formation: Phosphatidylcholine for lipid digestion
• Membrane phospholipid: Phosphatidylcholines main role
• Lipoprotein synthesis: Phosphatidylcholine moving lipids around to solubilize
• Neurotransmitter: Acetylcholine fired from neurons

Question 4

Major function of phospholipids

Answer 4

membrane structure

Question 5

Where is PC the primary phospholipid?

Answer 5

~60% of lipoproteins where outside is the PC and hydrophobic tails point inwards to hold fat soluble contents inside
* micelles
* VLDL or CM
* HDL

Question 6

Absorption, Uptake and Transport of choline

Answer 6

Dependent on the type of choline molecule.
* Lipid forms of choline (PC and SM) are primarily secreted from the intestine as part of CM and are important components of lipoproteins (secreted into lymph first)
* Aqueous forms of choline (Choline, betaine, etc) are taken up into cells by transporters and are found in free form in circulation (portal vein to liver first)

Question 7

Hepatic PC Biosynthesis

Answer 7

We can actually make choline and it is important for health consequences. Dietary choline is about health and biosynthesis is about survival.
* ~99% made by liver
* Adipose and testes can do some

Question 8

How is PC biosynthesized?

Answer 8

Makes choline via PEMT which involves 3 methylation reactions of PE to make the PC headgroup

Question 9

Adequate choline intake

Answer 9

AI reccomendations at 550 mg/day for men and 425 mg/day for women
* based on level of choline that prevented any signs of liver dysfunction

Question 10

Choline rich foods

Answer 10

Eggs, beef and liver high in PC

Question 11

Why are we interested in maternal choline during pregnancy and lactation?

Answer 11

• High demand by fetus and infant: Choline is essential for optimal infant brain development and cognitive function since they dont get the PC enzyme until after birth for biosynthesis
• Increased requirements during periods of rapid growth and development
• de novo synthesis alone cannot meet demands

Question 12

Choline reccomendations during pregancy and lactation

Answer 12

• pregnancy: 425 mg/d
• lactating: 450 mg/d

Question 13

APrON and choline

Answer 13

Estimation of choline intake from 24 hr dietary intake recalls and contribution of egg and milk consumption to intake amoung pregnant and lactating women in Alberta
* Did assessment during all three trimesters and 3 month post-partum (lactation)

Question 14

How did dietary foods containing choline change with the APrON study?

Answer 14

USDA only had about 634 foods so through analytical methods the alberta choline database develop a log of 2707 foods

Question 15

APrON: Choline intake across pregnancy and lactation

Answer 15

Only 16% of Alberta women in this cohort consumed the AI
* at least 20% didnt even consume half
* room for improvement here

Question 16

APrON: Who had higher choline intake during pregnancy % lactation?

Answer 16

Egg consumers

Question 17

APrON: Sources and forms of choline

Answer 17

• top dietary sources were dairy, eggs and meat making up about 45% of choline
• 5% of women consumed suppl. containing choline

Question 18

Recent finding on choline from animal studies

Answer 18

• Choline deficiency impairs intestinal lipid metabolism in the lactating rat. (JNB, 2015)
• Choline is required in the diet of lactating dams to maintain maternal immune function. (BJN, 2015)
• Feeding phosphatidylcholine compared to free choline in the maternal diet differentially affects immune development in the suckled offspring where PC improved immune function. (J Nutr, 2016)
• Choline deficiency during suckling restricts growth and impairs T cell expansion and function in offspring. (Eur J Nutr, 2017)

Question 19

Effect of choline in metabolic health

Answer 19

• Choline Deficient diets (CDD) impair VLDL secretion resulting in fatty liver.
• Animals fed CDD have low plasma cholesterol and TG levels because cannot get lipids out of liver
• Animals fed CDD have decreased intestinal integrity and have increased susceptibility to inducible-colitis

Question 20

global obesity epidemic

Answer 20

• T2D: 1 in 3 by 2050
• Fatty liver disease: 75% of obese/diabetics & 25% of Canadians
• CVD: leading cause of death in obese/ diabetic population

Question 21

How does extreme deficiency of choline usually occur?

Answer 21

When the biosynthesis enzyme PEMT does not work
* seen in knockout rats

Question 22

Consequence of PEMT knockout in rats

Answer 22

• impaired VLDL secretion
• comprimised membrane integrity
• comprimised bile secretion

Question 23

What happened to rats fed high fat diet with PEMT knockout

Answer 23

• quickly developed non-alcoholic fatty liver disease

BUT…
* but also gained less weight so protected against obesity
* Have an enhanced energy expenditure (higher O2 consumption)
* have improved glucose and insulin tolerance so protected against T2D

Question 24

Major problem with NAFLD

Answer 24

Major problem is the fat accumulation over decades bilds up and get macrophage build-up in the liver causing inflammation and get the fibrosis laying proteins down in place of liver cells

Question 25

What is the modulator for preventing weight gain in knockout rats?

Answer 25

choline is the modulator not betaine
* When choline was suppl. mice have normal EE and develop IR

Question 26

Does dietary choline deficiency reduce weight gain and IR with PEMT working?

Answer 26

PEMT mice fed a high fat diet without choline gained less weight then those with choline so similar results to knockout rats
* also had whole body increase in EE
* and improved glucose tolerance

Question 27

Does choline alter energy metabolism is insulin action in humans?

Answer 27

• Serum TG and glucose were decreased in subjects in the lowest quartiles of plasma choline.
• Plasma choline was positively correlated with BMI, percent body weight, and waist circumference.

The Hordaland Health Study

Question 28

Choline association with CVD seen in rats

Answer 28

Choline-Deficient Diet reduces plasma lipid levels in mouse models of cardiovascular disease
* knockouts have lower plasma lipids
* knockouts protected from atherosclerosis (~80% less risk)

Question 29

How might choline promote CVD?

Answer 29

Study from Wang et al. showed gut flora metabolism of choline may contribute to atherosclerosis
* Before getting absorbed the microbiome can take some choline and cleave off some which is taken up and goes to liver and is oxidized and forms TMAO molecule which is positively associated with adverse vascular events
* reccomended to avoid choline suppl. and eat vegetarian diet

Question 30

What is the problem with the Wang et al. study?

Answer 30

• The study used 10x the amount of reccomended choline which would be about 25 eggs
• based reccomendations on this that people should reduce choline intake
• researcher is vegan
• other studies could not reproduce similar results and even suppl. of dietary TMAO did not influence atherosclerosis development
• meta-analysis showed no association
• vegetarian diet contains plenty of choline
• does not consider other factors such as kidney function
• also possible that plasma TMAO is a marker of CVD risk not a cause