The Role of Fats & Cholesterol in our body and Which Supplements to take to provide protection and optimal health
Why Fats are important relative to cell membranes
Fats are macronutrients. The importance of fats in physiological systems is shown by the cell membranes. The cell membranes throughout the body’s different tissues and structures vary dramatically in their fat composition . It is these differences in fat composition that directly influence membrane function .
- Fatty acid shape physically regulates membrane function 
- Fatty acid composition influences membrane permeability 
For example, in most of the body, cell membrane phospholipids that each contain two fatty acids rarely contain the omega 3 fatty acid known as DHA (docosahexaenoic acid) whereas in the brain, 35 percent of all the phospholipids contain DHA . Furthermore, in the eye, photoreceptor phospholipids can contain up to 60 percent DHA .
- In developing infants especially, DHA composition in nervous system tissue has been suggested as contributory to conditions like attention deficit and hyperactivity disorder 
Tissue structures that are highly fat-dense seem to be influenced by both the amount and quality of fat .
- The myelin sheath that insulates the nerve cells is almost 80 percent fat . Changes in fatty composition of this sheath have been linked with dysfunction in a variety of myelinated nerves which include the sciatic and optic nerves 
Fat Classification and examples of each class
Though many healthcare providers have focussed on fatty acids in clinical practice, the category of nutritional fats includes more than fatty acids . Based on biochemical terms, fats are classified as lipids which are defined as substances that can be used by the body which are insoluble in water whilst being soluble in organic solvents like ether or chloroform . However it is important to note that the above definition of lipids is based on function rather than structure . Thus due to this functional definition, lipids actually include a wide variety of substances that are also classified in other ways .
Some examples of lipid derived molecules include :
-Vitamins and hormones
-Phospholipids, sphingolipids and glycosphingolipids
-many of the body’s universal regulatory substances like prostaglandins, prostacyclins, leukotrienes and thromboxanes
-Fat transport molecules like lipoproteins that make fats water-soluble to allow for blood transport
-Sterols like Cholesterol (which are found in cell membranes and serve as a starting point for bile synthesis, synthesis of vitamins and steroid hormones)
Unlike fatty acids, the basic building blocks for many types of fats, many of the above substances are not available from food and it is not fully understood as to how diet and lifestyle influences their synthesis . Research is still underway.
Fatty acids are the best known components of the lipid classification system . All share a consistent and fairly simple chemical identity (made up of carbon chains with a carboxyl group at one end and a methyl group at the other end) .
Fatty Acid Structure
- For chain lengths of six carbons and longer, even numbers of carbon atoms predominate 
- The carbon atoms may or may not be connected by double bonds . Any presence in one or more double bonds confers the fatty acid degrees of unsaturation thus giving them a description of being unsaturated 
- If only one double bond occurs, the fatty acid is further described as monounsaturated 
- If more than one double bond exist, they are designated as polyunsaturated 
- Saturated fatty acids contain no double bonds and vary in the body in carbon chain length ;
- Very short chain fatty acids(VSCFA) contain 2 to 3 carbons
- [e.g. acetic acid, propionic acid]
- Short chain fatty acids (SCFA) contain 4 to 6 carbons
- [e.g. butyric, valeric, caproic]
- Medium chain fatty acids (MCFA) contain 8 to 14 carbons
- [e.g.caprylic, capric, lauric, mycristic]
- Long chain fatty acids (LCFA) contain 16 or more carbons
- [e.g. palmitic acid, arachidonic acid(20 carbons), behenic acid (22 carbons), tricosanoic acid (23 carbons), lignoceric acid (24 carbons), cerotic acid (26 carbons)]
- All these fatty acids have research-proven functions in the body and are found in food or supplements 
Omega 3 and Omega 6
Researchers can start counting either from the methyl or the carboxyl end . Fatty acids that are named from the methyl end procedure are classified in terms of an omega number that is defined as the carbon atom initiating the first double bond when we count from the methyl end of the molecule .
In humans, three omega families of unsaturated fatty acids predominate, namely the omega 3, omega 6 and omega 9 families .
Humans and other mammals don’t synthesize desaturase enzymes that can insert a double bond closer than 7 carbon atoms away from the methyl end of the carbon chain . Therefore, humans are unable to convert omega 9 family fatty acids into omega 6s or omega 6s into omega 3s .
However, within each of these families, further elongation of the carbon chain and desaturation of the molecules is possible . Examples include:
- The Omega 6 fatty acid linoleic acid can be desaturated by the enzyme delta 6 desaturase into gamma linoleic acid but not into alpha linoleic acid.
- In contrast, the Omega 9 fatty acid oleic acid can be synthesized in the body from stearic acid (a saturated fatty acid)
- The above two statements indicated that at least two unsaturated fatty acids (linoleic acid; an omega 6 and alpha linoleic acid which is an omega 3) are required in the diet and dubbed as essential fatty acids (EFAs)
Relevance of the ratio of Omega 3 to Omega 6 fatty acids 
- Ratios of fatty acids between the different fatty acid families seem to play a critical role in a great variety of health conditions (e.g. cancer, skin-related disorders, immune-related disorders, endocrine-related disorders and cardiovascular disorders)
- High levels of Omega 9 fatty acids may indicate fat-related dysfunction (since the body’s production of Omega 9 fatty acids appear to increase when the supply of Omega 6 fatty acids is deficient)
- Inflammatory events also increase or are exacerbated by increased ratios of Omega 6 to Omega 3 fatty acids because the ratio of Omega 3 to Omega 6 fatty acids appear to be critical in balancing pro-inflammation eicosanoid synthesis from arachidonic acid
Arachidonic Acid Cascade
- This begins or is initiated with the release of arachidonic acid (AA) from cell membrane phospholipids through the activity of phospholipase A2 .
- It ends with the production of fatty-acid derived regulatory substances including the pro-inflammatory series 2 prostaglandins (PGE2S)
How cyclooxygenase and lipooxygenase each affect a different outcome in the Arachidonic Acid Cascade 
Arachidonic acid(AA), an omega 6 fatty acid containing 20 carbon atoms and four double bonds lies at the critical juncture in fatty acid metabolism .
*When cyclooxygenase acts upon AA, AA is converted into the series 2 prostaglandins (which leads to excessive inflammatory response) and prostacylins and series 2 thromboxanes .
*When AA is acted upon by lipooxygenase enzyme, it can be converted into the series 4 leukotrienes known as the eicosanoid molecules due to their 20-carbon length and pose oxidative risk .
- When eicosanoids are synthesized in excess, they promote chronic inflammation and are considered to be proatherogenic . On the other hand however, if eicosanoids are undersupplied, the body becomes inadequately supported during times of infection and injury 
- Part of the increased immune related risk associated with bottle feeding compared to breastfeeding involves the generous supply of AA in human milk versus an absence of AA in most plant-based formulas 
Role of Supplements
Lipid peroxides, free radicals and the use of Vit. E, C and Coenzyme Q as antioxidants
Polyunsaturated fats which contain several double-bond carbons are highly susceptible to oxygen damage through oxidative stress . Oxidative stress is a physiological condition where there is increased presence of reactive oxygen species (ROS) is not properly counterbalanced by the increased presence of oxygen metabolite-processing enzymes and free-radical quenching molecules . Biological oxidations are electron transfer reactions, thus the activities of reducing agents (electron donors) and oxidizing agents (electron acceptors) are needed to bring about redox reactions . If molecules are left with single unpaired electrons, these molecules become “free radicals” which are the most reactive type of ROS .
- Are fats that have been chemically damaged by oxygen free radicals 
- Levels of lipid peroxides have been correlated with increased risk of atherosclerosis, several cardiovascular conditions like cardiac ischaemia, cerebral ischaemia,and cancers, allergies, respiratory distress syndrome, thermal injury, irradiation, heavy metal toxicity and other free radical-generating conditions 
- F2-isoprostanes are prostaglandin molecules that are created through oxygen radicals interacting with membrane phospholipids. This makes them more susceptible to specific types of free radical damage to the lipid membrane 
- Any activity that require a substantial increase in oxygen intake or cause unexpected low oxygen concentrations (e.g. strenuous exercise) can place lipid structures at high oxidative risk 
Vitamin E as antioxidant
- Supplementation shown to reduce oxidative damage to muscle (when measured by reduced serum creatine kinase activity) 
- Indicators of protective effects are seen in alterations in fatty acid composition, Vitamin E concentration, lipid conjugated dienes in muscleand changes in urine lipid peroxides
- Can protect phospholipid bilayers of cell membranes and ability to scavenge free radicals
Vitamin C and lipid protection
- Long been identified as a free radical scavenger and also a key component in oxidative metabolism 
- Dietary deficiency has been shown to reduce oxidative capacity especially when exercising or during heightened activity 
- Involved in synthesis of Carnitine that is required for shuffling fatty acid substrate into the mitochondria for aerobic conversion to ATP
- At 1 gram per day level of Vitamin C supplementation, it has been shown to reduce exercise-induced oxidative stress and lipid-related damage and reduce lipid peroxidation (as measured by TBARS) 
Co-enzyme Q10 and lipid protection
- Reported uses for conditions like arrhythmia, atherosclerosis, cardiomyopathy and congestive heart failure 
- Cardiac muscle is one of the few tissues in the body that is continually aerobic and Coenzyme Q10 holds a central role in aerobic metabolism 
- Even though not directly involved in protecting lipid membranes, the synergy between Coenzyme Q10, Vitamin E and Vitamin C is important toward scavenging free radicals and reducing lipid peroxides in humans
- Coenzyme Q10 in its reduced form, helps reduce oxidized forms of Vitamin E 
- Redox potentials of Vitamins C and E are interlinked
- Supplementing with Coenzyme Q10 is important to nutritional protection of cell lipids 
Summary of the latest data on Cholesterol and why it is important to look at hormone regulation and immune status before attempting to regulate cholesterol leve
Cholesterol is a type of lipid belonging to the category of steroids that exists in all cell membranes 
- Cholesterol is vital in physiological functions like transmitting nerve impulses, forming Vitamin D, testosterone and oestrogen synthesis and formation of bile 
- About 80% of total body cholesterol is made in the liver and 20% comes from the diet
- There is homeostatic balance of cholesterol which is maintained accordingly i.e. when total cholesterol in the body increases, rate of liver synthesis decreases and vice versa. However, when dietary intake is chronically high, the ability of the liver to compensate with decreased production may become compromised
- Factors or risk factors that increase risk of hypercholesterolemia include low fibre intake, high sugar intake, caffeine intake, stress, lack of exercise, smoking and high fat intake if accompanied by nutrient deficiency 
- Cholesterol serves as a starting point for sterol-based synthesis of four critical regulatory hormones, cortisol, dehydroepiandrosterone (DHEA), testosterone and estrogen
- Cortisol in naturally secreted amounts help provide resistance to exogenous and endogenous stressors . Cortisol is the key glucocorticoid “counter-regulatory” hormone 
- DHEA is the most abundant steroid hormone in the body . While it has been shown to have anti-diabetogenic, anti-stress and weight-loss promoting effects, these effects are still not yet understood .
- Urinary excretion of DHEA is increased during emotional stress but DHEA levels are also significantly elevated in postmenopausal women with breast cancer probably because DHEA itself can be further converted to both estrogens and androgens . Therefore, more research is needed to see what the role of DHEA is in metabolic health 
- Cholesterol manipulation in the diet and the levels of cholesterol in the blood is a more complex phenomenon and cholesterol status may be intimately related to immune status and reproductive hormone balance 
In advising someone on dietary fats, what factors should be taken into consideration besides ‘how much’ fat is consumed? Why consider these other factors?
Short-Chain Fatty acids (SCFA)
- In clinical treatment of intestinal disorders, butyric acid (a SCFA) is especially effective due to it being the preferred fuel for the colonocytes 
- Butryrate administration shown to have anti-cancer effects in the colon, alter cancer doubling time, increase hyperavetylation of histones and inhibit DNA synthesis 
- Anaerobic bacteria in large intestine is capable of producing SCFAs if given adequate amount of specific substrate . About 50 to 60 grams of dietary carbohydrate rich in fiber is used to produce over 35 grams of SCFAs .
- Fiber substrates for SCFA production include : Soy polysachharide, pectin, guar gum, various vegetable fibers, lactulose and beta-glucan
- SCFAs administered colonically or enterally also shown to provide more direct support for colonic mucosa 
Medium Chain Fatty acids (MCFAs) and Medium Chain Triglycerides (MCTs)
- MCTs have been used to improve the health status of people with fat malabsorption problems .
- There are two reasons why MCTs are used . Firstly, like long chain fatty acids, MCTs can be taken up in the intestines into the circulation while bypassing certain physiological steps that are ordinarily required for fat uptake . Secondly, MCTs can be metabolized to usable forms of energy as rapidly as glucose which is regarded as the body’s most readily available form of energy 
- Coconut oil and palm kernel oil are the two most widely starting points for MCTs 
- Target of MCT preparation is to produce an oil that is high in shorted MCFAs namely caprylic (8-carbon) and capric (10-carbon) acids . MCT oils that contain 90 percent or more of these two MCFAs are the only MCT oils that are shown to be clinically effective in improving health status of compromised people 
In Syndrome X individuals, high fat diets with the right types of fats may be able to better support eicosanoid synthesis, avoid insulin hypersecretion and reduce dyslipidemia and insulin resistance . However, since the Western diet usually comprises of a high fat intake already, this recommended increased intake of dietary fat is not likely to help most patients . Therefore, reducing dietary fat is still likely to help without reducing total consumption to 20 percent or less of total calories consumed . The main thing is to recommend that one focuses on the overall fat quality of the foods eaten and derive as much dietary fat from whole, natural food sources especially plant sources beginning with seeds and nuts .Simply reducing dietary fat is not going to necessarily produce an improved health status because it through recognizing the roles that fats have in physiological functioning and structure that will bring us one step closer to establishing appropriate dietary and supplementary fatty acid intake for individuals . Furthermore, it is important to recognise the types of oils to use in high heat (Coconut, Peanut,High oleic Safflower), medium heat (Olive, Corn,Hazlenut) and low heating (Almond, Sunflower Butter, Sesame) conditions to prevent peroxidation of double bonds .
1)DeAnn Liska, Sheila Quinn, Dan Lukaczer et al.Clinical Nutrition-A Functional Approach, 2004, The Institute of Functional Medicine, a Nonprofit educational organization