Fatty acids

Fatty acids

hydrocarbon chain which have a carboxyl end and a methyl end.
Omega-3:
There are three double bonds located from the end of the methyl terminus
Omega- 6:
there are six double bonds located from the end of the methyl terminus

Fatty acids are transported in the blood by lipoproteins, (VLDL,LDL,HDL)
they have a role in the membranes as they are the phospholipid structure

Dietary n-3 fatty acids (Omega-3)
produce leukotrienes 5 and prostaglandins 3, which cause less inflammation and improved immunity, reduce swelling and pain

where as dietary n-6 fatty acids (omega-6)
produce leukotrienes 4 ad prostaglandins 2, which cause inflammation and dysregulated immunity swelling, pain, fever and redness

 

Fatty acids have various roles:

protein acylation - fatty acids can covalently bind to proteins, they play a key role in cellular structure and function, enables the proteins to be anchored to the membrane

lipid peroxidation - the more unsaturated a membrane is the more effected it is by lipid peroxidation. Induced by hydroxyl radicals, which are generated by phagocytes during immune activation. lipid peroxide is produced which is toxic to cells, and damages DNA by oxidation reactions. the risk of lipid peroxidation is reduced by ascorbic acid, a-tocopherol and selenium which leads to the production of catalase ( which decomposes hydrogen peroxide to water and oxygen)

gene expression - fatty acids bind to transcription factors, affecting the regulation of genes. they promote or inhibit the expression of genes e.g. TNF-a, COX-3, 5-LOX

Metabolic syndrome

A CLUSTER OF DISORDERS ASSOCIATED WITH RESISTANCE TO NORMAL INSULIN ACTION

tend to occur in the same people
usually have three of the following five abnormalities

hypertension >130 mm Hg

raised fasting blood glucose  > 100 mg/ dL this may or may not be related to diabetes  (pre-diabetes may occur, high enough to considered not normal or optimal).

tendency to carry weight around the waist, apple shaped, women >35 inches, men >40 inches
where we carry our weight is sometimes more important than

cholesterol profile - TAG > 150 mg/ dL, HDL ( the good cholesterol) < 40 mg/dL

nutrition and pregnancy

The information available on nutrition and supplementation is confusing and if often misleading, leaving the public immune or often misinterpreting information regarding nutrition and pregnancy. Here are a few points regarding the key issues, preconception,  during pregnancy and breastfeeding.

Weight and pregnancy

A healthy weight before and during pregnancy should be maintained. Before pregnancy the mother should have a BMI of between 18 and 25. Underweight mothers, mothers who carry out excessive exercise or have suffered amenhorrea ( >3 months of no period) in the past should be even more focused on maintaing a healthy weight, in order to prevent low birth rate and miscarrying the baby.  Obese people looking to become pregnant should also be considerate of their weight as a BMI >30 causes miscarrying and the implications associated with obesity, such as insulin resistant could put the baby at a genetic disposition to experience metabolic problems later in life.

Folic acid 

A supplement of 400mg a day is advised during pregnancy to prevent neural tube defects like spina bifida.  Food sources of folic acid can be found in: broccoli, kale, brussel sprouts, beans, legumes, and fortified foods such as cereals and marmite.
There is controversy over whether some foods should be regulatory fortified with high amounts of folic acid in them, yet the FSA has denied this fortification as folic acid as it can mask early signs of anaemia and vitamin B12 deficiency especially in the elderly causing neurological defects.

Vitamin D

Provided mainly from sunlight and absorbed by the epidermis layer in the skin, vitamin D is essential for the baby and their bones. A supplement of 10 mg per day should be advised particularly in people who are limited to sun exposure. Ethnic populations who are covered due to religion should also be aware of supplementation as they are more at risk due to reduced sunlight exposure.
Severe deficiency of vitamin D can lead to rickets,  decreased bone mineralisation, increase in fracture susceptibility,  and reduced bone size and mass.  "Healthy start" brand by the NHS provides the correct amount of vit D,C, and folic acid amounts.

Vitamin A

The amount of this vitamin should be limited. No more than 600 mg a day should be consumed in the diet or through supplementation ( always check other supplements do not contain any vitamin A). More than 800mg a day can be teratogenic. Vitamin A can be found in the diet in the form of carotenes and retinol. Foods containing high amounts should be avoided: pate, liver, kidneys. Excessive amounts can cause birth defects, such as a cleft lip and major heart defects.

Alcohol

If mothers are still going to drink during pregnancy, they should limit their consumption to one-two units twice a week.

Protein

There is no need in Western countries who consume a western diet, to increase protein intake, as the amount recommended is 60-85g which people already meet or exceed.

Smoking 

Smoking should be stopped during pregnancy, not only due to its 4,000 chemicals one cigarette contains but also due to the fact it restricts the oxygen flow to the baby making their heart work incredibly hard and faster potentially leading to death.

Fish

There is misleading messages on the NHS website and on various websites that may lead the pregnant women to avoid fish consumption completely. Yet research has said that the loss of nutrients from fish is far greater than the risk of harm from elements in the fish itself, so consumption of fish is still vital. Contamination from methyl-mercury is the main trace element of concern, therefore 1-2 portions of oil fish per week is advised, and no more than >3.3 ug/kg of body weight per week of fish like tuna, canned tuna, marlin, swordfish and shark should be consumed.
n-3 fatty acids from the fish (DPA,EPA,DHA) are essential fatty acid components of brain and retina cell membranes. Consumption of fish is particularly important in the third semester when there is a large increase in these membranes.  

Breastfeeding
breastfeeing should occur exclusively up to 6 months from the birth of the baby.
breastfeeding has many 

the sciencey bit...
a drop in estrogen and progesterone causes the primary milk let down in the breast of the mother and starts the process of the milk flow.
oxytocin and prolactin are regulated by a feedback loop, and cause the continual milk let down and the synthesis of milk. 
lactation provides all of the essential nutrients for the baby up to 6 months
the milk changes in the course of the six months providing different amounts of fat, nutrients and protein: colostrum - transitional milk - mature milk.
the milk also contains immune factors such as immune cells, antibodies and stem cells.
research has shown than 10% of early baby deaths can be prevented from breast feeding. 

Importance of breastfeeding
creates a bond between the mother and child
protection from early illness and diseases 
prevents eczema, asthma, childhood diabetes, chest infections
evidence suggests that breast feeding also prevents osteoporosis later in life 
it also aids weight loss if carried on for >6 months


Breastfeeding and HIV

HIV is mainly contracted through breastfeeding, this can be reduced by cessation of breastfeeding. Yet milk alternatives/formulas should be available with the correct amounts of vitamin and minerals. 
If breastfeeding is continued then antiretroviral therapy for both the mother and baby should be carried out.

Cancer - red and processed meat

CANCER

1.4 million cases world wide

highest rates 

men -

developed world: prostate

developing: lung

women- 

developed world- breast

developing - breast

cancer rates are only increasing

is the uncontrolled cell division resulting in loss of function and spread of cancer to other parts of the body (metastasis)

there is a disturbance in the cell cycle, and the growth of tumours are caused by the mutation in the DNA.

CAUSES :

1. GENETIC
2. CHRONIC INFECTION
3. LIFESTYLE

 GENETIC: high risk mutations and low risk polymorphisms BRCA1 and BRAC2 - which are linked to breast and ovarian cancer

LIFESTYLE: 

TABACCO:

each puff contains 60 carcinogens

formation of DNA -addcuts (DNA covalently bonded to a cancer-causing chemical)

there is an uptake of carcinogens and tumour promoters by hypermethylation

tumour supressor gene is inactivated

mutations in oncogenes, leads to loss of normal control mechanisms. 

UV:

exposure can cause neoplasms leading to leukaemia, breast and thyroid cancer.

Sunlight through the epidermis causes DNA damage and genetic mutations leading to tumour suppressor gene inactivated and cell cycle arrest of DNA repair.

MEAT:

positively associated with colon cancer

ammonia levels increase in the bowel after consumption of meat

the production of heam iron which can lead to production of free radicals

high intakes of red and processed meats.

N-nitroso compounds - found in meat, as used as a preservative, they act as potent carcinogens

PAH's (polycyclic aromatic hydrocarbons) - formed when meats are cooked/grilled over a flame at high temperatures. Once the meat is cooking the fat and juices will drip into the flame, and them rising form the flame is what contains the PAH's and stick to the meat.

HCA's (heterocyclic amines ) - formed when the amino acids and the creatine in the meat react at high temperatures during cooking. 

cooking ideas to reduce PAH's and HCA's:

• don't overcook foods
• make sure meat is thoroughly defrosted to reduce cooking time
• make sure the meat is not in direct contact with the flame
• remove any juices left over on the griller
• marinate the meat with lemon or vinegar as this works but covering the surface of the meat with a high acidity level, reducing the formation of HCA's.
• switching to grilled veg as they don't contain the creatine or amino acids that the meat contain forming the HCA's 

RECOMMENDATIONS:

To not eat more than 500g of red meat per week. This isn't that much if you think about the portion of a regular steak, a rump is usually 12 oz which is 340 grams, so if your having two steaks a week that's already over the recommended amount.

There is a recommendation to avoid processed meat completely. 

other dietary links with cancer....

LYCOPENE - found in high amounts in tomatoes
has an antioxidant effect (balances oxidative stress, scavenges reactive oxygen species)
improves immune function and reduces inflammation
it has an anti-proliferative effect (induces cell apoptosis - cell death which is needed in the uncontrolled devision of cells in cancer and works by decreasing cell growth arrest)

SELENIUM - high amounts found in brazil nuts contains Glutathione peroxidases, which are enzymes responsible for reducing the oxidative stress of the body.

The truth about Ageing and Nutrition

The maximum human lifespan is increasing significantly

There is also an increasing gender gap when looking at lifespans.

Women are living longer than men (sorry guys) due to :

1. The protective role of oestrogen (guys your never going to have these high amounts so just quit now)
2. Iron losses through the menstrual cycle 
3. General less stressful outlook on life (reduced CVD risk) 

Developed vs. developing 

there is a lower life expectancy in developing countries (less eduction, nutrition, reduced access to healthcare, government regulations)

Lifespan of species....

 Species with a higher metabolic live a decreased life, humans have a very slow metabolic rate compared to other species, hence we live longer than most animals. 

eg. a squirrel have a maximum lifespan of 7 years with a metabolic rate of:  1 litre of oxygen/kg/hour - 

There are 2 mechanisms of ageing:

1. FREE RADICAL THEORY 

a free radical: any species capable of independent existence that consists of one or more unpaired electron.

They are : highly reactive, can damage DNA, lipids and proteins, paramagnetic 

examples : hydroxy radical, hydrogen peroxide.

Theory is that cells in the human body over time accumulate free radicals, which ultimately leads to cell death. 

Free radicals start firstly off by removing the cells function and process, leading to then cell death.

free radicals work mainly by the process of a chain reaction, creating more free radicals than there where to start off with. A free radical  exposed to another molecule will want to find another electron, so that it becomes paired, and not unpaired. This causes the other molecule in which it is taking the electron from to be a free radical itself. This process then happens over and over. 

when there are no antioxidants in the body to inhibit/repair this process, a process called oxidative stress takes place. oxidative stress has been linked to cancers and CVD. (think oxidative stress occurs when there is an imbalance, a large amount of free radicals and no antioxidants)

the body is  always going to have free radicals as they are actually needed for certain body functions, so a continual balance in the body continually takes place, between the amount of free radicals and antioxidants. 

There are endogenous sources and exogenous sources (in the body and outside the body):

exogenous:

• sunlight (UV radiation)
• ionising radiation
• cigarette smoke
• alcohol and drugs (through oxidation)
• iron overload

endogenous 

• electron transport train - electrons leaking from the chain, superoxide production 
• Fenton reaction - metal catalyst redox reaction
• Haber weiss cycle  - metal catalyst redox reaction

how do we combat free radicals through nutrition ?

through antioxidants - these act as reducing agents, any substances that significantly delays or prevents the oxidation of a substrate.

we have produced intracellular antioxidants to combat the oxidative stress that takes place.

superoxide dismutase 

catalse

urate

GSH (gluthathione peroxidase) 

Dietary antioxidants:

Come from three main vitamins: A,C,E

vitamin C- ascorbic acid - red peppers, citrus fruits, blueberries, strawberries, kiwis, broccoli

vitamin E - a-tocopherol - advacados, tofu, spinach, almonds, shellfish

vitamin A - carotene- sweet potato, carrots, kale, red pepper 

2. GENETIC THEORY

this involved the science of chromosomes and DNA.

Telemores are structures found at the end of the DNA, they protect the end of the chromosomes from damage.

theory : as the cells approach senescence, the telemores shorten, exposing DNA to damage, through this shortening and exposure 200-250 base pairs are lost on the DNA, at each chromosome division. 

At each division the telemores of its daughter cells become shorter and shorter. 

Fat digestion and storage process

The roles of various organs and enzymes regulate the fat digestion and storage processes

FAT DIGESTION

The pancreas releases pancreatic lipase to hydrolyse the triglycerides into fatty acids. The gall bladder also functions here as it releases bile salts/acids, which combines the FA with the salts and acids, forming a mixed micelle.

The micelle moves into the aqueous interstitial space of the mucosa. Here the fatty acid is reformed into the TAG, through the process of mono-di- to triglyceride.

It is then transported out of the cell as a chylomicron ( these are the main dietary lipids which act as a transport for the fat from the intestines to other locations in the body)
the chylomicron moves into the lymphatic system via lactleas and from here can be distributed to the rest of the body. 


CHYLOMICRONS -
one of the five lipoproteins which transport fats in the blood.
main role is transporting dietary fats from the intestine to the rest of the body ( mainly fat digestion)
their remnants - after the fat as been moved to another part of the body, are taken up by the liver
they do not last long as the fat is broken down into fatty acids by other enzymes 

Fat storage  and breakdown process (lipolysis) 

Fat is stored due to the presence of insulin. 

Insulin is a hormone released by the beta cella of the pancreas.

Insulin levels increase after the consumption of glucose. Insulin works by various methods, here it works by decreasing fat breakdown and increasing the uptake and storage of fat.

This process is often linked to weight gain and relates to how a large intake of carbohydrates/glucose rich foods can promote fat storage and not fat breakdown. 

High levels of insulin, causes the release of lipoprotein lipase (LPL) from adipocytes (fat cells)

Once release LPL breaks down the TAG into fatty acids. This enables the absorption of fatty acids from the blood into the cells, where they are esterified back into TAG's for storage. The fat is then stored until further need.

A down regulation of insulin (low levels) caused by no glucose consumption (no sugar/candy, carbohydrates), or starvation causes an increase in the hormone glucagon  (various other hormones are also activated which have an effect on the liver, muscle and fat cells)which is also released from the pancreas by from the alpha cells.

This stimulates the release of hormone sensitive lipase (HSL) in the adipocytes. HSL breaks down the stored TAG into fatty acids which are the released into the blood. Albumin binds to the fatty acids so that they can travel in the plasma to reach certain sites in the body. 

Usually they travel to the liver where they can be used by the body for energy or broken down even further for other uses.

NOTE:

the first mechanism the body works by when in starvation, or having a limited amount of glucose in the diet, is by the process of glycogenolysis. Where the body breaks down any remaining glucose or store glycogen first. The body then moves onto stored fats (lipolysis, which is mentioned above) and then proteins through a process of gluconeogenesis. 

Essential fatty acids

Essential fatty acids commonly known as omega-3 and omega-6.

they are polyunsaturated fatty acids, 
omega translates as tail,
the number indicates where the first carbon double bond is (often referred to as nomenclature) 

As all fatty acids, there is a methyl terminus (CH3) and a carboxyl terminus (COOH)
e.g. for omega - 3, the double bond will be in the third position from the tail/methyl terminus of the fatty acid, giving us the name omega-3....

Metabolism of fat

they are known as essential fatty acids - as they cannot be metabolised by the human body. 
Synthesis can be via different starting metabolites.

Omega-6
these are found to be eaten more in the Western diet/world
they can be metabolised by the following pathway:
 LINOlEIC ACID (18: 2n-6) - 
GLA-
DGLA - 
ARACHIDONIC ACID (20:4n-6)

Omega-3
the high consumption of omega-6 to omega-3 is clear in the western world, mainly due to less consumption of fish.
It is metabolised in the following pathway 
a-linoelic acid (ala) (18:3n-3) - 
20:4n-3 - 
EPA (22:4n-3) -
DPA (22:5n-3) - 
DHA (22:6n-3)

Both of these processes go through a series of desaturation and elongation. 
They compete for the same enzymes through out the process, meaning that if dietary consumption of ALA or LA is higher than the other, one metabolism will be higher producing higher amounts of arachidonic acid or DHA.
In the western world, this is the case, as there is a higher consumption of LA, meaning there is an increased formation of arachidonic acid compared to DHA.

Deficiency of EFA's:
scaling dermatitis
rashes
poor wound healing
reproductive failure
renal failure
growth retardation

To avoid deficiency, EFA intake should be 1-2% of the daily energy intake

FATS/LIPIDS

the structure of fats

• Fats are composed of a carbon skeleton, with hydrogen and oxygen groups attached to the skeleton. 

• they are organic compounds, (meaning that they are a molecule containing carbon groups)

• OILS- liquid at room temperature

• FATS- solids at room temperature

there are four types of classes of fats 

1. simple - fatty acids esterified with alcohols (triglycerides)

1. derived - fatty acids esterified with alcohols and other groups (phospholipids - addition of a phosphate)

1. complex - fatty acids from the hydrolysis of of simple and derived fats

1. miscellaneous - vitamin E & K, carotenoids, 

90% of fats and oils are in the form of triglycerides/triaclyglycerols
they have the structure of a glycerol backbone with three fatty acids joined to the backbone.


when we talk about saturated/ sat fat, trans fat, or unsaturated fat, we are referring to the carbon carbon double bonds in the fatty acid carbon chain

saturated fat - has no carbon carbon double bonds
unsaturated fat - has carbon carbon double bonds
monounsaturated fat - 1 c-c double bond
poulunsaturated - 2 or more c-c double bonds
trans fat - are the result of a process called hydrogenation which adds hydrogen to the chain, and makes the fat harden, giving various properties to the structure. these fats have been known to be associated with CVD due to them increasing low density lipoproteins and decreasing the amount of high density lipoprotein circulating in the plasma. 


Examples :
saturated - palmitic, stearic, myristic
unsaturated - oleic, vaccenic
polyunsaturated - arachidonic, linoleic 


FAT recommendations
total fat intake should be no more than: 35%
saturated fat - 11%
MUFA - 13%
PUFA - 6.5%
TRANS FAT - no more than 2%