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Lectures Public Health Nutrition (PHN)Lecture 1: trans fatty acids and health
Outline:
1. What is myocardial infarction?
2. Industrial trans fatty acids
3. Legislation
4. Natural trans fatty acids
5. CLA
What is myocardial infarction MI?
Myocardial infarction is mostly linked to the intake of trans fatty
acids. A MI is caused by occlusion (blockage) of an artery
Myocardial infarction is caused
On the right side you see a heart with a MI. you have an artery that
is occluded. There is a blockage in the artery. This part of the heart
does not get any blood and oxygen. That parts starves= MI.
Bad and good cholesterol:
LDL deposes cholesterol in arteries. 50-80% of cholesterol in blood is
LDL-cholesterol
HDL takes up cholesterol from cells. 20-40% of cholesterol in blood is HDL-cholesterol
The artery gets occluded because LDL cholesterol deposes in the arteries.
LDL cholesterol may end up in plaques in arteries:
LDL: the bad carrier of the cholesterol in blood
Cholesterol-rich plaque in artery -> Plaque is cholesterol rich.
MYOCARDIAL INFARCTION IS CAUSED BY BLOCKAGE OF CORONARY ARTERIES BY PLAQUES. CHOLESTEROL IS AN
IMPORTANT COMPONENT OF PLAQUES
Industrial fatty acids:
The factory workers needed bread and butter, but the problem was that butter was expensive so they were
searching for alternatives.
The hardening of edible oils through hydrogenation: you can make oils hard which means that you can spread
them.
If you do full hydrogenation you will get saturated fats
If you do partial hydrogenation you get more or less the same molecule
TRANS versus CIS:
Cis and trans. Composition is the same but the elaidic is in the trans form
instead of the cis which is the case in oleic acid.
SIS= kink in molecule
TRANS= straight
Kink or straight has large implications for the molecule.
due to the straight shape of the fatty acid chains, fatty acids in the trans
configuration are harder than fatty acids in the cis configuration.
Straight molecules are hard fats.
1
,Advantage of process of making trans fat: you can determine how much you made and how hard the margarine
will be. The hardness of the trans can be finetuned
Industrial trans fatty acids:
originate from hydrogenation (partial) of vegetable oils
Alternative to butter
Control over hardness margarine
Very important for industry: This meant that you can make oil into a spread.
Industrial trans fatty acids and serum lipoproteins:
Industrial trans fatty acids raise LDL cholesterol and lower HDL cholesterol compared to unsaturated fatty acids
and carbohydrates
You can expect more cholesterol deposit in the plaques and more plaque formation
Effect of industrial trans replaced by cis mono unsaturated fat on LDL cholesterol:
If you replace trans by SIS unsaturated that has a positive effect on LDL cholesterol.
Effect of replacing industrial trans on cholesterol:
If you replace industrial trans by for example cis LDL cholesterol goes down
which is important for the risk on CVD.
TRANS FATTY ACID INTAKE IS POSITIVELY ASSOCIATED WITH THE RISK OF
HEART DISEASE IN COHORT STUDIES: 5 extra grams (2en%) of trans per day is
associated with a 25% increase in coronary heart disease risk (pooled RR 1,23)
Conclusion artificial trans fat:
Artificially made trans fatty acids raise the risk of heart disease
They do that by raising LDL cholesterol and lowering HDL cholesterol which causes plaque formation,
occlusions and myocardial infarction.
Legislation:
They went to the margarine industry and told them this is what happening when eating trans fat. Together they
said we need to solve this and to take the trans fat out of margarines.
In the Netherlands the industry took action: Industrial trans fatty acids were removed from food. No legal
action from the government.
Saturated and trans fatty acids in Dutch margarines:
Since the end of the 90’s the amount of trans fats is minimalized.
Intake of fatty acids:
The intake of everybody is below <1 en% (that is what we want)
Change in intake of trans fats in time:
In the Netherlands it is below <1en%. In the US it is much higher. In Denmark they banned trans fat in 2001
Effect of Danish ban:
Huge differences between Denmark and their ban compared to the US who did nothing
2
,Legislation USA/FDA:
No Longer Generally Recognized as Safe
In 2013, FDA made a preliminary determination that PHOs were no longer “generally recognized as safe,” or
GRAS, for short. FDA is finalizing that action and determining that PHOs are not GRAS for any use in human
food.
The federal government on Tuesday moved to ban the trans fats found in some of Americans' favorite snacks,
from popcorn and pies to frozen pizzas and cinnamon rolls.
The rule by the Food and Drug Administration notes that partially hydrogenated oils – the primary source of
artificial trans fats in processed foods – are no longer generally recognized as safe for use in food. Under the
rule, food companies have three years – until June 18, 2018 – to remove them from products in grocery
stores.
2013: the FDA in the USA decided that the PHOs (partially hydrogenated oils) were no longer recognized as
save (GRAS). They did not really say something about trans fats but the process to make trans fat (lobby for the
industry)
2018: remove PHO from products
Remarkable action industry in EU:
An open letter from major manufactures including nestle has called on the European commission to legislate an
EU-wide limit for the amount of industrially produced trans fats in foods.
Why would big companies do such things? they already had removed the trans fat out of their product.
Open letter – oct 15 2015:
Subject: Call for a legislative limit for the amount of industrially produced TFAs in foods
BEUC, CPME, EHN, EPHA, Kellogg Company, Mars, Mondelēz and Nestlé are concerned about the health effects
of trans fats from partially hydrogenated oils.
We therefore respectfully call on the European Commission to propose a legislative limit for the amount of
industrially produced TFAs in foods to 2 gram per 100g of fat.
This is in accordance with EFSA’s recommendations to minimize trans fats in the context of a nutritionally
adequate diet and the recent WHO Europe Policy Brief on "Eliminating Trans Fat in Europe" (Sept 2015).
Yours sincerely,
BEUC, CPME, EHN, EPHA, Kellogg
Company, Mars, Mondelēz, Nestlé.
Action eu:
2 grams per 100 grams of fat
3
,Industrial trans fatty acids are disappearing from foods. How about trans fatty acids from animal sources?
Two sources of trans fat:
1. Industrial hydrogenation -> “artificial” trans fats
2. Biohydrogenation -> “natural” animal trans fats (takes place in the
stomach of the cow)
a. Vaccenic acid
b. Conjugated linoleic acid = CLA
There are 2 predominant sources of dietary trans fatty acids (TFA) in the food
supply, those formed during the industrial partial hydrogenation of vegetable
oils (iTFA) and those formed by biohydrogenation in ruminants (rTFA),
including vaccenic acid (VA) and the naturally occurring isomer of conjugated
linoleic acid, cis-9, trans-11 CLA (c9,t11-CLA)
What is animal trans fat?
In reality it is not so easy to say this one is industrial and this one is natural
Elaidic double bound on 9th position, counting from the methyl end.
Distribution of trans isomers in milk and industrial fats:
As soon as the fat has a trans it is a trans fat but FDA looks at it differently; if its
conjugated we do not consider it a trans fat, so CLA is not a trans fat in the US
Conjugated fatty acids are polyunsaturated fatty acids in which at least one pair
of double bonds is separated by only one single bond.
Oleic is a CIS fat because it only has a double bond in the cis configuration
Vaccenic acid is major present in milk. Elaidic is one of the major forms of trans
fat in PHO but it is also present in milk. They both contains the same trans fatty
acids but not in the same amounts. The distribution is different but they have
exactly the same molecule structure. In the blood it is impossible to see whether
it comes from an industrial or natural source. It is hard to distinguish if it comes
from a industrial or ruminant source.
Effect of ruminant versus industrial trans fatty acids on heart disease risk?
1. In observational studies, high intake of artificial trans fatty acids predicts coronary heart disease
2. Intake of ruminant trans fatty acids is low, and association of ruminant trans fatty acids with heart disease
in observational studies is unclear
Is there other evidence?
There are more studies done with industrial trans fat, you
can easier investigate higher amounts,
Quantitative review: conclusion:
Industrial and animal trans fatty acids both raise LDL
What does the EU with ruminant trans fat?
CLA:
4
,CLA = conjugated linoleic acid
High doses in supplements
CLA is also part in milk and dairy products and meat, but the amount of CLA is very low. It has a trans and a cis
bond.
CLA trial: conclusion:
The effect of CLA and industrial trans on HDL, LDL, LDL/HDL was similar:
The ruminant animal trans fatty acid CLA has the same effect on LDL and HDL as industrial trans fatty acids
CLA supplements:
3 maal daags 1-2 (softgel)capsules met water tijdens de maaltijd innemen. De
(aanbevolen) dosering niet overschrijden.
It supposes to help you lose weight. You take 6 grams of CLA per day it will have an
effect on you LDL and cholesterol levels.
5
,Lecture 2: dietary guidelines for the prevention and management of T2D
Topic exam question is when is the evidence sufficient to go to a guideline?
When would you think evidence is good enough to do recommendations that apply for all people/diabatic
people?
Content:
• Diabetes
• Diet and the development of diabetes
• Dietary guidelines for the prevention and management of diabetes
• Debate on the use of a low carbohydrate diet
Type 2 diabetes:
• Hyperglycemia
• Insulin resistance & reduced insulin secretion
• Diagnosis with symptoms (thirst, polyuria, fatigue) after 5-10 years hyperglycemia: complications already
present
• Alternatively early detection through screening
Type 2 diabetes is characterized by hyperglycemia, developed due to insulin resistance which is the Insensitivity
of the tissues to insulin to take up sufficient amounts of glucose or reduced pancreatic insulin secretion, leading
to high blood glucose levels.
Insulin resistance is the main characterization for type 2 dm. it is a lifestyle related disease, often driven by
obesity leading to insulin resistance. Reduced insulin secretion plays a little less of a role in the life style related,
obese related type 2 diabetes.
Diagnosis is made when symptoms occur. High levels of blood glucose are often already present before
complaints occur.
Worldwide prevalence of diabetes:
Worldwide prevalence of diabetes increases:
- We are getting older
- but also, the obesity pandemic plays a large role
- In combination with the improved management of diabetes: people live longer with diabetes which also
leads so a higher prevalence.
It is a public health burden that is increasing over time.
Diagnosis of pre-diabetes and diabetes:
Pre-diabetes is an early state where people are at an increased risk. Blood glucose levels can also go back to
normal glycemia.
The diagnosis can be made on fasting plasma glucose, 2-hour plasma glucose or HbA1c.
You can either have impaired glucose tolerance where you have an increased 2-hour plasma glucose but a
normal fasting glucose or an impaired fasting glucose which is increased levels of fasting glucose but perhaps
not yet on the two hours fasting glucose.
When you meet 1 of these thresholds you are diagnosed with type 2 diabetes. In routine practice someone is
diagnosed either when they have symptoms and 1 measurement of increased blood glucose or without
symptoms with 2 occasions where someone tests positive for plasma glucose or HbA1c.
(You do not need to know the cutoffs by heart, just know that they are used)
type 2 diabetes is an important risk factor for
cardiovascular disease:
6
,On the left side you see the macrovascular complications
On the right side you see microvascular complications
Retinopathy: eye problems
Neuropathy: foot ulcers
The aim of treatment is to prevent macro and microvascular complications.
Lowering glucose concentrations either by oral glucose lowering agents or by insulin. Hba1c is used as
treatment target. They often also get blood pressure and cholesterol lowering treatment. They reduce the risk
of major cardiovascular diseases.
lifestyle intervention and risk of diabetes
Diabetes prevention program:
placebo had the highest risk for diabetes. Lifestyle was the most effective. Metformin was
in between.
PREDIMED: Effect of a Mediterranean diet on risk of diabetes:
The Mediterranean diet was either supplemented with nuts or olive oil and it showed a
risk reduction. Adding to this debate, there were some protocol deviations. Includement
without randomization, assignment to the wrong study group. So they analyzed the data as if it were an
observational study and found the same effect: risk reduction for cardio vascular diseases.
There was a lot of debate on this study: you are not completely sure whether you are studying the effect of the
Mediterranean diet by itself or are you just studying the effect of nuts and olive oil?
Against this background, richtlijnen goede voeding (Dutch dietary guidelines)had been made, these are also the
basics for people with diabetes. We want an increased intake on fruit and vegetables, fish, tea, nuts, legumes,
whole grains (instead of refined). An optimum consumption of diary, filtered for unfiltered coffee, unsaturated
fat sources instead of saturated fat sources. Reduction of red and processed meats, salts, sugar sweetened
beverages and alcohol beverages.
A lot of focus is on the medical treatment (bloodglucose, cholesterol and bloodpressure
lowering agents), with little reference to diet and lifestyle.
2019 EASD guideline for the management of type 2 diabetes:
They recommended the Mediterranean diet with nuts/olive oil which comes directly
from the PREDIMED study. You can debate whether you still want to use this study as
basis for your recommendations.
Proposal:
A Mediterranean diet is recommended by the EASD and ESC to reduce risk of
cardiovascular disease in people with type 2 diabetes. Agree/Disagree/Comment
NDF dietary guideline 2015:
Aims:
1. Delay or prevent type 2 diabetes
2. II. Reduce acute complaints of hyper- or hypoglycaemia
3. III. Delay or prevent complications
4. IV. Maintain an adequate dietary pattern
Prevention of type 2 diabetes:
Lifestyle intervention for body weight related health risks
“Combined lifestyle intervention” consists of:
- Calorie restricted diet with attention for improvement on long term (> 1 year)
- Increased physical activity
7
, - If needed psychological intervention to support behavior change
It is often difficult for people to stick to the diet or maintain weight.
• Advise according to Dutch Dietary Guidelines
• Quality of fat and carbohydrates is more important than quantity
Treatment of diabetes:
Type 1 diabetes
• Emphasis on alignment of dietary pattern and carbohydrates with insulin to reach an optimal
regulation of diabetes to prevent or delay complications.
Type 2 diabetes
• Emphasis on maintaining or reaching a healthy body weight, as 80% of people with type 2 diabetes are
overweight by sufficient physical activity and reducing the risk of complications.
Treatment of diabetes with overweight:
• Recently diagnosed: aim for 5-10% body weight reduction
• At short-term (< 1 year) carbohydrate reduced diet is beneficial in terms of body weight, lipids and
cardiovascular risk than fat reduced.
• Intensive lifestyle programs with professional guidance for dietary, physical activity and behavior change
are preferred
BMI >30 kg/m2, comorbidities or insufficiently regulated
• Low Calorie Diet (1000 kcal/day)
• Very Low Calorie Diet (500 kcal/day/meal replacement)
Quick reduction of body weight, improved glycemic control and reduction of cardiovascular risk factors
With longer duration of diabetes, in consultation with patient, more attention towards prevention of weight
gain than reduction of body weight
NHG-standaard:
• For each patient: no smoking, sufficient physically active, weight reduction when BMI>25, healthy diet, if
necessary refer to dietician
• Healthy diet: according to Dutch guidelines; reduce saturated fat, increase unsaturated fat, increase fibre
intake and little alcohol, no supplements
The importance of lifestyle modification is acknowledged but the place it haves in the medical treatment is still
limited. Probably physicians find it difficult to do.
Treatment of type 1 and type 2 diabetes:
Carbohydrates/ protein/ fat
• No specific en% target for macronutrients
• According to different dietary patterns: Mediterranean and low carbohydrate
• Replacement of high glycaemic products by low glycaemic products slightly improves glycaemic control.
High glycemic index: Carbohydrate foods that are broken down quickly by your body and cause a rapid increase
in blood glucose
Low glycemic index: Carbohydrate foods that are broken down slowly by your body and cause a slow increase
in blood glucose
Saturated fat
• Intake of saturated fat has a negative impact on body composition.
• Advise to reduce saturated fat and replace by mono- or poly unsaturated fat
Trans fat
• Trans fat increases cardiovascular risk factors
8
,Omega-3 fatty acids
• Food products high in omega-3 fatty acids improve cholesterol levels
• Do not advise for omega-3 supplements
Saturated fat, trans fat and omega 3 are in line with the Dutch dietary guidelines.
Vitamin b12:
• Metformin > vitamin B12 deficiency
• Prevalence of 6-33% with metformin use
• Dependent on (cumulative) dose: The higher the dose the lower b12 levels.
• Consequences: Neuropathy, depression, cognitive function
The use of metformin (first line drug) leads to a deficiency of vit B12.
Advise vitamin b12:
• Screening for vitamin B12 deficiency in metformin users is not advised > insufficient evidence
• Check in certain situations:
• Serum vitamin B12
• Methyl malonic acid
• 1 mg daily oral/ 1 mg monthly parenteral
Vitamin D:
No effect of vitamin D supplementation on type 2 diabetes or Hb1Ac in people with diabetes.
We are not screening and supplementing people unless there is sufficient evidence: we know that the
deficiency occurs but the effect on the consequences is not clear, also the efficacy of treating the b12
deficiency is not sufficient investigated.
Alcohol consumption:
• Do not consume more than 1 glass alcohol per day
• > Extra carbohydrates due to hypoglycaemic effect of alcohol (only for diabetic)
Alcohol can have a hyperglycemic effect and can lower the blood glucose at a later moment.
Moderate levels of alcohol do not seem to be a harm so that is way you should restrict to 1 a day.
Statement
Lifestyle intervention should be prioritized above medical treatment in the management of type 2 diabetes
Low carbohydrate or low fat dietary pattern?
• Not indicated in general Dutch dietary guidelines
• Low carbohydrate diet provided as an option in the diabetes guideline
• Low fat diet not provided as option
• Based on what evidence?
Proposal:
A low carbohydrate diet is preferred over a low fat diet to prevent complications in people with type 2
diabetes. Agree/ disagree
Agree, but adherence goes down Low carbohydrate diet
Lecture 3: health effects of folate: current evidence
Lecture content:
• Folate and folic acid
• Folate – adverse pregnancy outcomes
9
, • Optimizing folate intake - strategies
• Folate, homocysteine and cardiovascular disease (CVD)
• Folate, homocysteine and cardiovascular disease – cont.
• Folate and other diseases
Folate and folic acid
Folate and folic acid – b11:
• Folate present in food
– Main food sources: vegetables, fruit, grains (plant based foods)
– Recommended daily intake:
• 300 μg/dayg/day
• Folic acid supplement 400 μg/dayg/day for 4 weeks before -> 8 weeks after conception
– Upper limit (NL): 1000 μg/dayg/day
– Intake folate equivalents diet: 258 μg/dayg/day (284 μg/dayg/day, 231 μg/dayg/day): the intake in men is higher
than in women; men eat more
Dutch National Food Consumption Survey (VCP) 2012-2016, RIVM, 2016
Sometimes it is called b9
Folate is used for the dietary form
Folic acid is used for the supplement, synthetic form
Pregnant women should take 400 ug a day 4 weeks before and 8 weeks after conception
Functions of folate:
• DNA metabolism
• Amino acid metabolism
Folate metabolism:
Folate comes in, it has a role on the left side, the DNA synthesis.
On the right side it has a role in the amino acid metabolism. Those 2 are
linked.
DNA synthesis:
When you eat folate, it is transformed to 5,10 methylene THF
(tetrahydrofolate). Together with B2, it is set to 5-methyl THF. When the 5-
methyl group is taken off, it goes back to THF. The methyl group can be given to the amino acid pathway.
Amino acid metabolism:
Proteins are broken down in amino acids, methionine is one of the amino acids and can be broken down into
homocysteine, which is also an amino acid. Homocysteine can be broken down to cysteine with the help of B6,
but it can also go back to methionine with the help of B12, together with the methyl group of folate.
Folate and DNA synthesis:
• Folate deficiency reduces DNA synthesis
• Cell division disturbed
– Red blood cells -> megaloblastic anemia
When DNA synthesis, cell division is disturbed which has its effect on red blood cells. Megaloblastic anemia is a
clinical sign of deficiency of folate.
Folate – adverse pregnancy outcomes
Folate and neural tube defects (NTD):
• During embryo development cell division is extremely rapid.
• Neural tube develops from day 21-27 post conception (not all women know that they are pregnant)
10
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