The lipids are the third class of macronutrient. They are as ubiquitous in the diet as proteins and carbohydrates, where they occur predominantly as storage lipids called triglycerides (formed from fatty acids), and cholesterol, a lipid with roles in both cell structural and communication.

Fatty acids are the building blocks of most lipids. These energy-rich molecules come in a variety of configurations, each with different chemical and physical properties to serve a diversity of functions. The long, straight, tightly stacked molecules of saturated fatty acids predominate in the rigid solid fat deposits in animals; the loose associations of the molecularly kinked unsaturated fatty acids allows them to stay liquid and form the oils of vegetables, seeds, and fish. The kinks in unsaturated fatty acids are a result of the type of chemical bonds between atoms within the fatty acid (double bonds for the chemically-inclined). Fatty acids can vary in length, and amount of saturation (monounsaturated fatty acids have one double bond, polyunsaturated can have several). Unsaturated fatty acids can also be in cis- or trans- configurations, which refers to the nature of the double bonds within the acid. Trans-fatty acids produced by the chemical hydrogenation of oils have gained particular notoriety for their potential to increase the risk of heart disease, while naturally-occurring trans fats (such as conjugated linoleic acid from milk products) can be beneficial.

Although fatty acids can be taken up from the diet, the body is well equipped to synthesize its own for energy storage or structural purposes. The exception is the two essential fatty acids which cannot be synthesized by mammals and must be obtained through the diet: alpha-linolenic acid, an omega-3 fatty acid; and linoleic acid, an omega-6 fatty acid. Given adequate amounts of these two compounds, and the body’s enzymatic machinery, the entire repertoire of fatty acids can be constructed.

Much of the fats and oils in the diet are in the form of triglycerides, which are storage lipids formed of a molecular complex of glycerol and three fatty acids (unsaturated, saturated, or mixtures of the two). Other sources of dietary fatty acids include phospholipids (which form cell membranes), mono- and di-glycerides. Whatever the source, dietary fats and oils are broken down by the action of digestive enzymes secreted from the pancreas and intestines (called lipases) to release individual fatty acids, which are absorbed from the small intestine, packaged into new triglycerides or phospholipids, and distributed throughout the body to serve their various roles.

Cholesterol is a type of lipid distinct from the fatty acids, triglycerides, or phospholipids. It is a waxy, steroid compound that has critical roles in metabolism. The human body makes the majority of its own cholesterol, although some is obtained through the diet: dietary sources of cholesterol are exclusively animal products (plant sources of cholesterol are extremely rare and appear to be limited to certain types of algae).1 To partition cholesterol into “good” and “bad” varieties is a bit misleading; there is only a single type of cholesterol in nature. Elevated levels of blood cholesterol (or more accurately, elevated levels of cholesterol that are contained in specific types of lipid particles called low density lipoproteins) have been implicated in the progression of atherosclerosis, the progressive accumulation of fatty deposits in arteries that can lead to serious cardiovascular consequences. However, cholesterol’s association with heart disease risk obscures its many critical roles in metabolism, from serving as a building block to many hormones, to ensuring the proper firing of nerve impulses.

Roles of Fats and Cholesterol in Normal Metabolism Dietary lipids have several potential fates in human metabolism:

Fuel Source and Fuel Storage. Triglycerides, and the fatty acids they contain, are a rich source of cellular energy. While glucose is the preferred energy source for most cells, glucose is a bulky molecule that contains little energy for the amount of space it occupies (glucose is stored in the liver and muscles as glycogen, which is used to power the brain and muscles between meals). Not only are fatty acids better sources of energy on a per-weight basis (one gram of carbohydrate contains 4 kilo-calories of energy, compared to 9 kilo-calories/gram for triglyceride), but they are denser, giving them the ability to store massive amounts of energy in fat deposits. The average human, for example, can only store enough glucose as glycogen in the liver for about 12 hours worth of energy, but can store enough fat to power the body for significantly longer (up to several days during starvation).

Because fatty acids are superior for storing excess energy, excess dietary carbohydrates are converted into fatty acids and packaged into triglycerides for long-term storage. However, this conversion is one-way; fatty acids cannot be converted back to glucose. This presents a problem for some cells (like neurons in the brain), which do not metabolize fatty acids, and do not have access to the vast energy stores of adipose tissue. In times of carbohydrate deficit (such as during starvation or low-carbohydrate dieting), fatty acids are converted into ketone bodies, an alternate source of fuel for brain cells.

Building blocks of cell membranes. Lipids form the bulk of the membranes which surround each cell in the body; these lipids are predominantly formed of phospholipids and cholesterol. It is here that the importance of cholesterol becomes apparent; its “waxy” nature helps to keep the membranes around cells fluid, so that cells are viable at a wider range of temperatures. Some cells have a particularly heavy reliance on cholesterol for proper function: The membranes surrounding healthy liver cells, for example, are almost one-third cholesterol,2 and cholesterol is a major component of the myelin sheath that surrounds neurons and allows for these cells to transmit electrical impulses rapidly over long distances.3 Mitochondria, the centers of energy generation in most cells, also rely heavily on cholesterol to insulate against the loss of electrolytes during their generation of ATP.4

Precursors to hormones. Cholesterol is used as the starting material in the synthesis of all of the bodies steroid hormones, which include the sex hormones (testosterone, progesterone, and the estrogens), mineralcorticoids (which control the balance of water and minerals in the kidney) glucocorticoids (which control protein and carbohydrate metabolism, immune suppression, and inflammation), and vitamin D (which controls calcium and phosphate balance). Omega-3 and omega-6 fatty acids from the diet are used to synthesize eicosanoids, a set of hormone-like molecules that are important for a diverse set of metabolic functions, including inflammation/anti-inflammation, blood clotting, immune function, response to allergens, protection from stomach acid, and parturition (labor).

Digestion and Absorption of Fats. Cholesterol is the starting material for bile acids, a group of detergent-like molecules that are synthesized in the liver, and used to emulsify/solubilized many dietary fats and cholesterol. This facilitates the absorption of dietary lipids in the intestines.

Many of the health benefits realized by modifying lipid intake involve altering patterns of consumption: reducing intake of saturated, trans-fats, and cholesterol, and increasing intake of mono- and polyunsaturated fats. Omega-3 intake, in particular, has been the subject of hundreds of studies in humans and animals, in part for its ability to successfully reduce the risk of several diseases by different mechanisms:

Reducing Chronic Low-level Inflammation. Diets high in saturated fats have been associated with an increase in proinflammatory markers in some studies, particularly in diabetic or overweight individuals.5, 6 The intake of synthetic trans-fats has also been associated with increases in markers of inflammation in some studies,7, 8 although this data is conflicting and may be more pronounced in individuals that are also overweight.9, 10 Omega-3 fatty acids have been studied for their prevention of cardiovascular disease and mortality in tens of thousands of patients; the anti-inflammatory effects of omega-3’s are thought to contribute to this activity.11 Several small studies of omega-3 fatty acid consumption have demonstrated their beneficial effects against other inflammatory diseases, particularly asthma, IBD, and rheumatoid arthritis.12, 13 These clinical trials are supported by several large observational trials encompassing thousands of patients, which have revealed inverse relationships between fish oil/omega-3 consumption and markers of systemic inflammation within diverse populations.14-17

Promoting Healthy Blood Pressure. Omega-3 fatty acids consumption has led to significant reductions in blood pressure across several clinical trials. In a survey of 36 clinical trials on the effects of omega-3 supplementation in over 2000 individuals, a median intake of 3.7 g/day of fish oil demonstrated an average reduction of blood pressure of 2.1 mm Hg (systolic) and 1.6 mm Hg (diastolic).18 In hypertensive individuals, the average reductions in blood pressure were much greater, amounting to -4 mm Hg (systolic) and -2.73 mm Hg (diastolic). When compared to low-fat diets, Mediterranean diets (moderate fat diets characterized by high intakes of monounsaturated fats from nuts and olives, and polyunsaturated fats from fish) demonstrated average reductions of 1.7 mm Hg (systolic) and 1.5 mm Hg (diastolic) over six studies including more than 2600 individuals.19 While these reductions may seem very small, it is important to remember that even modest reductions in blood pressure can have significant effects on cardiovascular health; for example, lowering diastolic blood pressure by 5 mm Hg has been estimated to lower the risk of stroke death by 40 percent and the risk of death by heart disease or other vascular causes by 30 percent.20

Promoting Healthy Levels of Blood Lipids. The effects of fish oil fatty acids on the reduction of serum triglycerides (a cardiovascular risk factor) are well established. Forty-seven studies with over 15,000 patients, have demonstrated an average triglyceride reduction of 30 mg/dL, at an average intake of 3.35 g fish oil over 24 weeks.21 The effects of fish oil fatty acids on LDL and HDL cholesterol are equivocal.22 (Prescription fish oil uses a highly concentrated esterified fatty acids that provides a dosage of 3.36 g of omega-3 in 4 capsules; its degree of triglyceride reduction—up to 45 percent—is similar to non-prescription fish oil at a similar dose, but requires less capsules.23) High monounsaturated and polyunsaturated fatty acid intake typical of Mediterranean diets have demonstrated reductions in serum triglycerides and total cholesterol, when compared to low-fat diets.19

As with the case of carbohydrates, there are opposing opinions on the optimal amount and composition of lipid for a healthy diet. There is general agreement that synthetic trans-fats should be avoided. The majority of expert opinions suggest that cholesterol and saturated fat intake (particularly from animal sources) be minimized; the USDA RDIs suggest these values at < 300 mg/day and < 20 grams/day (~10 percent of total calories in a 2000 calorie diet) respectively. The National Cholesterol Education Program’s Therapeutic Lifestyle Changes (TLC) diet suggests more conservative daily intakes of < 200 mg/ day cholesterol and < 7 percent of total calories from saturated fats.24 Beyond these recommendations, however, is a substantial schism between proponents of low-fat/higher carb and low-carb/ higher fat diets. There is evidence that both diets can reduce disease risk and maintain a healthy body mass index.25

As for the benefits of omega-3 fatty acids in particular, the majority of clinical studies on the effects of fish oil for cardiovascular health and inflammation looked at intakes of 3–4 grams of omega-3 fatty acids per day, which is a considerable amount to consume from fish alone (200 –400 grams of fatty fish per week provides between 500 and 800 mg of omega-3’s per day).26 Significant health benefits have been observed at these lower levels of fish oil consumption in some observational studies.16, 26

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