Human Nutrition Vocabulary

Fiber

• The generic recommendation for adults is 25g to 40g of fiber daily.
• These recommendations can be met by ingesting:
  • Whole-grain products (1 to 2 g of fiber/serving)
  • Vegetables (2 to 3 g of fiber/serving)
  • Fruits (about 2 g of fiber/serving)
  • Legumes (6 to 8 g of fiber/serving)
• For specifics about serving sizes, refer to the Canada Food Guide.

Lipids

• Main types of lipids found in foods:
  • Fatty acids
  • Triglycerides (TG)
  • Phospholipids
  • Sterols
• Lipids participate in various processes:
  • Energy production (fatty acid oxidation)
  • Energy storage (TG accumulation)
  • Insulation and padding (TG stored in adipose tissue)
  • Cell signaling (diacylglycerol, DAG)
  • Structural support (cell membrane formation)
  • Inflammatory responses (eicosanoids)
  • Hormonal production (steroids)
• Lipids are generally insoluble in H_2O and require specific processes for digestion, absorbance, and transport in the body.
• Lipids are abundantly present in foods such as butter, margarine, nuts, oils, lard, cheddar cheese, hamburger, salmon, eggs, avocado, etc.
• Cholesterol is only present in animal foods.
• Health Canada suggests a diet that is low in saturated fat, trans fat, and cholesterol.
• 20 to 35% of the daily energy intake should be provided by lipids.

Fatty Acids

• Simplest of the lipids, containing methyl (non-polar) and carboxyl (polar) ends that do not cyclize.
• Classified according to:
  • Chain size:
    • Short-chain: 2 to 4 carbons
    • Medium-chain: 6 to 12 carbons
    • Long-chain: 14 to 26 carbons
  • Saturation:
    • Saturated: no double covalent bonds (e.g., palmitic acid)
    • Unsaturated: presence of double covalent bonds
• Nomenclature reflects the degree of saturation:
  • Monounsaturated (MUFA): one double bond (e.g., oleic and palmitoleic acids)
  • Polyunsaturated (PUFAs): two or more double bonds (e.g., linoleic and arachidonic acids)
• Numeric representation:
  • 16:0 (palmitic acid) - 16 carbons, 0 double bonds
  • 16:1 (palmitoleic acid)
  • 18:1 (Oleic acid)
  • 20:4 (arachidonic acid)
  • The first number indicates the number of carbons, and the second the number of double bonds.
• Double bond position:
  • Delta ($\Delta$) system: counts carbons from the carboxyl end.
    • Example: Linoleic acid - 18:2$\Delta^{9-12}$
  • Omega ($\omega$) system: counts carbons from the methyl end.
    • Example: Linoleic acid - 18:2$\omega$-6
• All dietary fats are a mix of polyunsaturated, monounsaturated, and saturated fatty acids in varied proportions.
  • Butter: mostly saturated, but contains some monounsaturated and polyunsaturated fatty acids.
  • Oils: mostly unsaturated, but contain small amounts of saturated fatty acids.
• The length of the fatty acid and the degree of unsaturation influence its solubility and melting point.
  • Shorter fatty acids are more water-soluble.
  • Greater number of double bonds increases polarity and water solubility.
  • Longer chain length and more saturation increase the melting point.
  • Unsaturated fatty acids are liquid at room temperature, except for oleic acid.

Examples of Naturally Occurring Fatty Acids

• Saturated Fatty Acids:
  • Myristic acid (14:0): Coconut oil and most animal/plant fats
  • Palmitic acid (16:0): Animal and plant fats
  • Stearic acid (18:0): Animal fats and some plant fats
  • Arachidic acid (20:0): Peanut oil
  • Lignoceric acid (24:0): Small amounts in peanut oil
• Unsaturated Fatty Acids:
  • Palmitoleic acid (16:1$\Delta^{4(-7)}$): Mostly marine animal oils
  • Oleic acid (18:1$\Delta^{(w-9)}$): Plant and animal fats
  • Linoleic acid (18:2$\Delta^{9,12(-6)}$): Corn, safflower, soybean, sunflower seed, poultry fat, nuts
  • $\alpha$-linolenic acid (18:3$\Delta^{9,12,15(-3)}$): Canola and flaxseed oil, soybean, nuts and seeds
  • Arachidonic acid (20:4$\Delta^{5,8,11,14(-6)}$): Small amounts in animal fats
  • Eicosapentaenoic acid (20:5$\Delta^{5,8,11,14,17(-3)}$): Marine algae and fish that feed on algae
  • Docosahexaenoic acid (22:6$\Delta^{4,7,10,13,16,19(-3)}$): Phospholipid component of animal fat, marine algae, and fish that feed on algae

Essential Fatty Acids

• Not synthesized by the body; must be obtained through diet.
• Linoleic (18:2$\Delta^{9,12 (-6)}$) and $\alpha$-linolenic (18:3$\Delta^{9,12,15 (-3)}$) acids
• Humans lack $\Delta2$ and $\Delta15$ desaturases, which are enzymes crucial to incorporate double bonds at such positions.
• Plants have these enzymes.
• Complete abolishment of fat from diet can lead to:
  • Retarded growth
  • Dermatitis
  • Kidney lesions
  • Early death

$\omega$-3 and $\omega$-6 Fatty Acids

• Great nutritional interest in recent years.
• Often exert opposing metabolic effects.
• $\omega$-3 fatty acids:
  • Associated with reduced blood pressure and blood clots
  • Reduced risks of heart disease and stroke
  • Improved defense against inflammatory diseases
• $\omega$-6 fatty acids:
  • Can have a pro-inflammatory effect and be harmful
• Ideal ratio between $\omega$-6 and $\omega$-3 fatty acids was thought to be important, but no scientific evidence exists to support any recommendation based on these ratios.
• Consensus: increase intake of dietary $\omega$-3 fatty acids.
• Canadian Food Guide recommends two servings of fish a week, emphasizing fatty fish like salmon, herring, and mackerel.
• Fish should be grilled, baked, or broiled instead of fried.
• Alternative: dietary supplements (fish oil capsules).
  • Concern: excessive intake can cause bleeding, interfere with wound healing, raise LDL, and suppress immune function.
  • Use should be carefully monitored.

Trans Fatty Acids

• Most unsaturated fatty acids in nature have hydrogens located next to the double bond on the same side of the carbon chain (Cis-fatty acids).
• Small fraction of naturally occurring fatty acids have hydrogens next to the double bonds on the opposite side of the carbon chain (Trans-Fatty acids).
• Industry uses hydrogenation to add hydrogens to unsaturated fatty acids.
• Partial hydrogenation can leave some double bonds with a trans configuration, creating trans fatty acids.
• Advantage of hydrogenation: protects fatty acids against oxidation and prolongs shelf life; alters texture.
• Intake of trans-fat associated with increased heart disease:
  • Raises LDL (bad cholesterol)
  • Lowers HDL (good cholesterol)
  • Increases weight gain
  • Promotes visceral fat accumulation
  • Induces inflammation
• Big push to eliminate trans-fat from processed foods.
• Food labels required to specify amount of trans-fat per serving.

Triglycerides (TG)

• Largest proportion of lipids humans consume.
• Found in foods like salad dressing, butter, margarine, cooking oil, nuts, dairy products, bacon, beef, and skin of chicken.
• Composed of three fatty acids esterified to one glycerol molecule.
• Abundantly found in adipocytes in white adipose tissue as energy storage and insulator.
• Visceral adipose tissue provides mechanical support for internal organs.
• TGs serve as carriers of lipid-soluble vitamins (A, D, E, K), confer taste to food, and signal for satiety.
• Fatty acid composition of TGs determines whether lipid is liquid or solid at room temperature.
  • More saturated fatty acids: solid
  • More unsaturated or short-chain fatty acids: liquid
• TGs stored in white adipose tissue can be mobilized for energy under food restriction/increased energy expenditure.
• Lipolysis cleaves TGs into fatty acids (non-esterified fatty acids, NEFAs) and glycerol.
• NEFAs bind to albumin for transport in circulation.
• Albumin facilitates NEFA uptake by organs.
• Skeletal muscles, heart, and liver take up NEFAs for $\beta$-oxidation.
• Liver converts glycerol into glucose through gluconeogenesis.

Catabolism of TGs and Fatty Acids

• Hydrolysis of TGs yields glycerol and three fatty acids.
• Inside the cell, fatty acids are activated by the attachment of coenzyme A to form acyl-CoA (irreversible, consumes 2 ATPs).
• Acyl-CoA undergoes oxidation for energy production in the mitochondria.
• Short-chain fatty acids (SCFAs) pass directly into the mitochondrial matrix, while long-chain fatty acids (LCFAs) require a transport system.
• Carnitine is the carrier molecule for LCFAs.
• Acyl-CoA joins carnitine covalently at the outer mitochondrial membrane, and carnitine:acyltransferase (CAT I) moves acyl-carnitine across the inner membrane.
• A second transferase (CAT II) splits acylcarnitine to form acyl-CoA and carnitine.
• Acyl-CoA undergoes $\beta$-oxidation, sequentially cleaved in two-carbon units (acetyl-CoA), which enter the Krebs cycle.
• Complete $\beta$-oxidation of palmitate (16-carbon fatty acid) yields about 106 ATP molecules.
• Net ATP production from complete catabolism of glucose (6-carbon sugar) is 32 ATP molecules.
• Glucose \space C6H{12}O6 + 6O2 + 32(ADP+Pi) \rightarrow 6CO2 + 32ATP + 38H_2O
• Palmitate \space C{16}H{32}O2 + 23O2 + 106(ADP + Pi) \rightarrow 16CO2 + 106ATP + 122H_2O

Phospholipids

• Composed of glycerol, two fatty acids, and a phosphate group (PO_4).
• Amphiphilic molecules: attract both water- and fat-soluble substances.
• Structural components for cellular membranes (double layer).
• Carbon 1 ($\alpha$ carbon) is esterified to a saturated fatty acid, and carbon 2 ($\beta$ carbon) is esterified to an unsaturated fatty acid.
• Carbon 3 is attached to a phosphate group.
• Phospholipids vary by what is attached to the phosphate group.
• Common variants:
  • Phosphatidylcholine (lecithin): choline bound to the phosphate group
  • Phosphatidylethanolamine (cephalin): ethanolamine bound to the phosphate group
  • Phosphatidylserine: serine bound to the phosphate group
  • Phosphatidylinositol: inositol bound to the phosphate group
• Phospholipids attract H_2O because they are more polar than TGs and sterols.
• Positioned on the surface of chylomicrons, stabilizing them in aqueous solution.
• Present in cell and organelle membranes, serving as conduits for H_2O and fat-soluble material.
• Provide compounds for eicosanoid synthesis, intracellular signaling, and cell anchorage.
• Regulate cellular functional roles by keeping fatty acids, choline, and other biologically active substances bound and freeing them only as needed.

Sterols

• Characterized by a four-ring core structure (cyclopentanoperhydrophenanthrene) or steroid nucleus.
• Cholesterol is the most common sterol in animals, serving as a precursor for other steroid molecules.
• Human enzyme systems are specific for cholesterol and do not react with plant sterols.
• Plants have other sterols but not cholesterol.
• Major dietary sources of cholesterol: meats, egg yolk, poultry, and dairy products.
• Sterols along with phospholipids comprise about 5% of dietary lipids.
• Liver cells make about 800 to 1500 mg of cholesterol every day.
• Liver cells use cholesterol for bile production, which is important for dietary lipid digestion.
• Cholesterol is abundant in brain and nerve tissues.
• Promotes plaque formation and the development of atherosclerosis.
• Control of circulating cholesterol levels is a common practice to prevent or treat cardiovascular diseases.
• Cholesterol is not an energy-producing nutrient, catabolism and elimination is through the biliary system.
• Removal of bile salts is a therapeutic approach to treat hypercholesterolemia, using unabsorbable resins.
• Plant sterols (phytosterols) are poorly absorbed and may inhibit the absorption of cholesterol.

Endogenous Cholesterol Synthesis

• Body can synthesize cholesterol, so it is not needed in the diet.
• Most cholesterol (90%) in our body is inside cells; liver and intestine are primary sites.
• Acetyl-CoA is the precursor utilized to synthesize cholesterol.
• Glucose and fatty acids are the main substrates catabolized to generate acetyl-CoA in the mitochondria.
• Cholesterol synthesis pathway:
  1. Conversion of Acetyl-CoA into mevalonate
  2. Mevalonate into squalene
  3. Squalene into cholesterol
• Pathway regulated by the amount of cholesterol present in the cell.
• Rate-limiting enzyme hydroxymethylglutaril-CoA (HMG-CoA) reductase catalyzes the conversion of HMG-CoA to mevalonate and is inhibited by cholesterol.
• Allows the cell to regulate its rate of cholesterol production.
• Endogenous production is low/high with elevated/reduced dietary cholesterol supply, respectively.

Digestion and Absorption of Lipids

• Lipids need to be broken into smaller compounds.
• Lipids are generally not soluble in H_2O, digestion requires specialized system
• Salivation and mastication at the oral cavity allow lingual lipase to start TG hydrolysis at the sn-3 position
• Continues at the stomach where gastric lipase promotes further lipid digestion.
• Lingual and gastric lipases preferentially hydrolyze TGs containing short- and medium-chain fatty acids.
• Fat entering the duodenum is ~70% TGs with the remainder composed of partially hydrolyzed lipid products
• Most TGs are digested in the intestine, requiring bile salts and pancreatic lipase.
• Bile released by the gallbladder has amphipathic properties, causing emulsification of lipids.
• Pancreatic lipase hydrolyzes ester bonds at the sn-1 and sn-3 positions of the glycerol moiety.
• Detergent-like action of bile acids, combined with peristaltic agitation, turns fat into small droplets with greatly increased surface area (emulsification)
• Pancreatic juice also contains colipase, which binds lipase and reverses the inhibition by bile salts.
• Only a small fraction of TGs is totally hydrolyzed to free glycerol.
• Products of TG digestion contain 2-monoacyl-glycerols (2-MAGs) and free fatty acids.
• Other lipids such as phospholipids and cholesterol esters have their ester bonds cleaved by phospholipases and cholesterol esterase.
• Products of lipid digestion contains primarily, 2-MAGS, 1-MAGs, lysolecithin, cholesterol and free fatty acids.
• Lipids combine with bile salts to form negatively charged aggregates called micelles.
• Micelles can now interact with the microvilli at the brush border and allow the movement of lipids into the enterocytes.
• Absorption of fatty acids occurs in the distal duodenum and jejunum through protein independent (diffusion model) and protein dependent (mediated by fatty acid transport proteins, FATP 1-4, as well as by FAT/CD36) mechanisms.
• Absorption of free cholesterol is also an energy-independent process, mediated by transporter proteins.
• Once inside the enterocytes, LCFAs and cholesterol are diverted to the endoplasmic reticulum where the former is converted again into TGs and the latter into cholesterol esters.
• Two enzymes (acyl-COA:cholesterol acyltransferases 1 and 2 (ACAT1 and ACAT2) esterify cholesterol, but not plant sterols.
• Bile acids, formed from cholesterol in the liver, are not absorbed with the contents of the mixed micelles, they are absorbed from the terminal part of the ileum by an energy requiring process and re-enter the portal vein.
• The liver then reuses bile salts, this is known as the "enterohepatic circulation"
• The remaining unabsorbed (~1 g/day) is modified by bacteria in the intestine and subsequently excreted in the feces.
• Estimated that a total of 2.5 to 4 g of bile acids is recycled about twice with each meal.
• Rapid turnover, about 18 g/day of cholesterol leaves in the form of bile salts and most of it (~17.5 g) is reabsorbed.
• Free cholesterol is also secreted in the bile (~1 g/day) and about half of this is reabsorbed.
• Net loss of cholesterol and bile acids is about 1 g/day, which is basically matched by the input from diet and endogenous synthesis.
• Pharmacological interventions to block the re-absorption of bile and promote its elimination through the feces have been used to force the liver to convert more cholesterol into bile.
• With this approach, the goal is to deplete the body's cholesterol pool through an increase in bile production to compensate for its accelerated excretion through the feces.

Lipids and Coronary Artery Disease

• The notion that dietary fat is associated with the development of coronary artery disease (CAD) is widely promoted and accepted, despite great controversy that exists on the subject.
• The "diet-heart hypothesis", developed during the 50's and 60's, was based on the idea that dietary saturated fat elevated circulating cholesterol levels leading to the development of CAD.
• Indeed, there is evidence that lipid infiltration within the intima layer of arteries progressively increases as atherosclerosis advances.
• However, this does not imply that elevated circulating cholesterol causes CAD.
• Data used to support the "diet-heart hypothesis" originated from correlational studies that have been heavily criticized due to fraudulent data analysis, also dismissing/ignoring randomized clinical trials that contradict the hypothesis that saturated fat and cholesterol cause CAD.
• Surprisingly, data do not support the claim that elevated intake of saturated fat is the culprit for the increase in CAD in North America and other western societies.
• Heart disease deaths increased during the 19th century despite unchanged consumption of saturated fat during this period.
• Consumption of vegetable oils (particularly seed oils) that markedly increased in the last century.