🥦Advanced Nutrition Unit 2 – Macronutrients – Advanced Concepts

Key Macronutrients Recap

• Macronutrients provide energy and essential building blocks for growth, repair, and maintenance of the human body
• Carbohydrates are the body's primary energy source and include simple sugars (monosaccharides, disaccharides) and complex carbohydrates (oligosaccharides, polysaccharides)
• Proteins are essential for building and repairing tissues, enzymes, hormones, and immune system components, consisting of amino acids linked by peptide bonds
• Lipids include triglycerides, phospholipids, and sterols, serving as energy storage, cell membrane components, and signaling molecules
  • Triglycerides are the primary form of dietary fat and are composed of three fatty acids attached to a glycerol backbone
  • Phospholipids are key components of cell membranes, consisting of a hydrophilic head and hydrophobic tail
• Water is often considered the fourth macronutrient due to its essential role in physiological processes and nutrient transport
• Macronutrient balance is crucial for optimal health, with recommended ranges of 45-65% carbohydrates, 10-35% protein, and 20-35% fat of total daily energy intake

Advanced Carbohydrate Metabolism

• Carbohydrate digestion begins in the mouth with salivary amylase and continues in the small intestine with pancreatic amylase, breaking down complex carbohydrates into monosaccharides
• Monosaccharides (glucose, fructose, galactose) are absorbed by enterocytes in the small intestine and transported to the liver via the portal vein
• Glucose is the primary energy source for most cells and is tightly regulated by hormones such as insulin and glucagon
  • Insulin promotes glucose uptake by cells and storage as glycogen in the liver and muscles, while glucagon stimulates glycogen breakdown and glucose release during fasting
• Glycolysis is the first step in glucose metabolism, converting glucose to pyruvate in the cytosol and generating ATP and NADH
  • Pyruvate can enter the mitochondria for further oxidation in the citric acid cycle or be converted to lactate under anaerobic conditions
• Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors (amino acids, lactate, glycerol) in the liver and kidneys, maintaining blood glucose levels during fasting or prolonged exercise
• Pentose phosphate pathway is an alternative route for glucose metabolism, generating NADPH for biosynthetic reactions and ribose-5-phosphate for nucleotide synthesis
• Fructose metabolism occurs primarily in the liver, where it is converted to glycolytic intermediates or triglycerides, potentially contributing to non-alcoholic fatty liver disease when consumed in excess

Protein Structure and Function

• Proteins are polymers of amino acids, with each amino acid consisting of an amino group, carboxyl group, hydrogen atom, and a unique side chain (R group)
• The sequence of amino acids in a protein is determined by the genetic code and is crucial for its structure and function
• Primary structure refers to the linear sequence of amino acids, held together by peptide bonds formed through condensation reactions
• Secondary structure describes the local folding patterns of the polypeptide chain, such as $\alpha$-helices and $\beta$-sheets, stabilized by hydrogen bonds between the amino acid backbone
  • $\alpha$-helices are right-handed spiral conformations, with 3.6 amino acids per turn and hydrogen bonds between the carbonyl oxygen and the amino hydrogen of every fourth residue
  • $\beta$-sheets are formed by extended polypeptide chains that are either parallel or antiparallel, with hydrogen bonds between the backbone of adjacent strands
• Tertiary structure is the three-dimensional arrangement of a single polypeptide chain, determined by interactions between side chains (hydrophobic, ionic, hydrogen bonding, disulfide bridges)
• Quaternary structure refers to the assembly of multiple polypeptide subunits into a functional protein complex, stabilized by the same interactions as in tertiary structure
• Protein folding is a complex process guided by the amino acid sequence and cellular chaperones, with misfolding leading to aggregation and potential disease states (Alzheimer's, Parkinson's)
• Proteins serve diverse functions in the body, including structural support (collagen), transport (hemoglobin), enzymes (digestive enzymes), hormones (insulin), and immune defense (antibodies)

Lipid Biochemistry Deep Dive

• Lipids are a diverse group of hydrophobic molecules, including fatty acids, triglycerides, phospholipids, and sterols
• Fatty acids are long-chain carboxylic acids, classified as saturated (no double bonds), monounsaturated (one double bond), or polyunsaturated (multiple double bonds)
  • Essential fatty acids (linoleic and $\alpha$-linolenic) cannot be synthesized by the body and must be obtained through the diet
  • Omega-3 (EPA, DHA) and omega-6 (arachidonic acid) fatty acids are important for cell signaling, inflammation, and brain development
• Triglycerides are the primary form of energy storage in adipose tissue, consisting of three fatty acids esterified to a glycerol backbone
  • Lipolysis is the breakdown of triglycerides into free fatty acids and glycerol, stimulated by hormones such as epinephrine and glucagon
• Phospholipids are the main components of cell membranes, with a hydrophilic head (phosphate group and polar molecule) and two hydrophobic fatty acid tails
  • The arrangement of phospholipids in a bilayer allows for selective permeability and compartmentalization of cellular processes
• Sterols are lipids with a four-ring structure, the most common being cholesterol in animal cells and ergosterol in fungal cells
  • Cholesterol is a precursor for steroid hormones (estrogen, testosterone, cortisol), vitamin D, and bile acids, and plays a role in cell membrane fluidity
• Lipid metabolism involves the synthesis and breakdown of fatty acids, triglycerides, and cholesterol
  • Fatty acid synthesis occurs in the cytosol, using acetyl-CoA as a substrate and NADPH as a reducing agent
  • $\beta$-oxidation is the breakdown of fatty acids in the mitochondria, generating acetyl-CoA for the citric acid cycle and NADH and FADH2 for the electron transport chain
• Lipid transport in the bloodstream is facilitated by lipoproteins, which are classified based on their density and composition (chylomicrons, VLDL, LDL, HDL)
  • Imbalances in lipoprotein levels can contribute to the development of atherosclerosis and cardiovascular disease

Macronutrient Interactions

• Macronutrients interact in various ways to influence energy balance, metabolism, and health outcomes
• Carbohydrate and protein intake can affect insulin secretion and sensitivity
  • High glycemic index carbohydrates lead to rapid increases in blood glucose and insulin, while low glycemic index foods result in slower, more sustained release
  • Protein consumption stimulates insulin secretion, but to a lesser extent than carbohydrates, and can improve insulin sensitivity
• Protein and carbohydrate metabolism are interconnected through the glucose-alanine cycle
  • During fasting or exercise, muscle protein is broken down into amino acids, which are converted to pyruvate or TCA cycle intermediates for energy production
  • Alanine, a key glucogenic amino acid, is transported to the liver for glucose synthesis via gluconeogenesis
• Fat intake can influence carbohydrate and protein metabolism
  • High-fat diets can lead to insulin resistance and impaired glucose tolerance, particularly when combined with a sedentary lifestyle
  • Omega-3 fatty acids (EPA, DHA) have anti-inflammatory properties and can improve insulin sensitivity and reduce the risk of cardiovascular disease
• Macronutrient balance and distribution across meals can affect appetite, satiety, and energy expenditure
  • Protein is the most satiating macronutrient, followed by carbohydrates and fats
  • Consuming a balanced distribution of macronutrients at each meal can help regulate hunger and promote weight management
• Macronutrient timing around exercise can optimize performance and recovery
  • Consuming carbohydrates before and during prolonged exercise can maintain blood glucose levels and delay fatigue
  • Post-exercise protein intake (particularly branched-chain amino acids) can stimulate muscle protein synthesis and repair

Energy Balance and Metabolism

• Energy balance refers to the relationship between energy intake (calories consumed) and energy expenditure (calories burned)
  • Positive energy balance (intake > expenditure) leads to weight gain, while negative energy balance (intake < expenditure) results in weight loss
• Total daily energy expenditure (TDEE) consists of three main components:
  • Basal metabolic rate (BMR): the energy required to maintain basic physiological functions at rest, accounting for 60-70% of TDEE
  • Thermic effect of food (TEF): the energy expended in digesting, absorbing, and metabolizing nutrients, representing 10-15% of TDEE
  • Physical activity energy expenditure (PAEE): the energy used during exercise and non-exercise activity thermogenesis (NEAT), varying based on individual activity levels
• Factors influencing BMR include body composition (lean mass vs. fat mass), age, sex, genetics, and hormonal status (thyroid hormones, growth hormone)
• Adaptive thermogenesis is the adjustment of energy expenditure in response to changes in energy intake or environmental conditions
  • During caloric restriction, the body may reduce BMR and NEAT to conserve energy, making sustained weight loss more challenging
• Macronutrient composition can affect energy expenditure and substrate utilization
  • High-protein diets have a higher TEF compared to high-carbohydrate or high-fat diets, potentially aiding in weight management
  • Low-carbohydrate diets may lead to increased fat oxidation and ketone production, but long-term effects on health and weight loss are controversial
• Physical activity is a key modulator of energy balance and can increase TDEE, improve body composition, and enhance insulin sensitivity
  • Resistance training helps maintain or increase lean body mass, which is metabolically active and contributes to a higher BMR
  • Cardiovascular exercise promotes fat oxidation and can create a caloric deficit for weight loss

Macronutrients in Disease States

• Imbalances in macronutrient intake and metabolism can contribute to the development and progression of various chronic diseases
• Obesity is characterized by excessive body fat accumulation, often resulting from a combination of genetic, environmental, and behavioral factors
  • Excess calorie intake, particularly from high-fat and high-sugar foods, coupled with insufficient physical activity, can lead to weight gain and obesity
  • Obesity is a major risk factor for insulin resistance, type 2 diabetes, cardiovascular disease, and certain cancers
• Type 2 diabetes is a metabolic disorder characterized by hyperglycemia due to insulin resistance and impaired insulin secretion
  • High intake of refined carbohydrates and saturated fats can exacerbate insulin resistance and contribute to the development of type 2 diabetes
  • Dietary management focuses on controlling carbohydrate intake, increasing fiber consumption, and favoring healthy fats (monounsaturated and omega-3) to improve glycemic control and reduce cardiovascular risk
• Cardiovascular disease (CVD) encompasses conditions affecting the heart and blood vessels, such as coronary artery disease, stroke, and hypertension
  • High intake of saturated and trans fats can raise LDL cholesterol levels and increase the risk of atherosclerosis and CVD
  • Dietary patterns rich in fruits, vegetables, whole grains, lean proteins, and healthy fats (Mediterranean diet, DASH diet) have been shown to reduce CVD risk
• Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the liver, often associated with obesity and insulin resistance
  • High intake of fructose and saturated fats can contribute to the development of NAFLD by promoting de novo lipogenesis and hepatic triglyceride accumulation
  • Dietary interventions for NAFLD include reducing added sugar and saturated fat intake, increasing omega-3 fatty acid consumption, and promoting weight loss through calorie restriction and physical activity
• Protein-energy malnutrition (PEM) is a condition resulting from inadequate intake of protein and/or calories, leading to impaired growth, development, and immune function
  • PEM can occur in both undernutrition (kwashiorkor, marasmus) and overnutrition (sarcopenic obesity) settings
  • Treatment involves providing adequate protein and energy intake, addressing micronutrient deficiencies, and gradually refeeding to avoid refeeding syndrome

Current Research and Controversies

• The role of dietary fat in health and disease remains a topic of ongoing research and debate
  • While the link between saturated fat intake and CVD risk has been well-established, the effects of specific types of saturated fatty acids (e.g., medium-chain triglycerides) are being investigated
  • The optimal balance of omega-6 to omega-3 fatty acids for inflammation and disease prevention is an area of active research
• The efficacy and safety of low-carbohydrate and ketogenic diets for weight loss and metabolic health are subjects of controversy
  • Some studies suggest that low-carbohydrate diets can lead to greater short-term weight loss and improved lipid profiles compared to low-fat diets
  • However, concerns exist regarding the long-term sustainability and potential nutrient deficiencies associated with severe carbohydrate restriction
• The impact of dietary protein on kidney function, particularly in individuals with pre-existing kidney disease, is a topic of ongoing investigation
  • While high protein intake has been associated with increased glomerular filtration rate (GFR) and potential kidney strain, the long-term effects on kidney health in healthy individuals remain unclear
• The role of the gut microbiome in mediating the effects of macronutrients on health and disease is an emerging area of research
  • Dietary fiber and resistant starch have been shown to promote the growth of beneficial gut bacteria (Bifidobacterium, Lactobacillus) and the production of short-chain fatty acids (butyrate, propionate)
  • Interactions between the gut microbiome and host metabolism may influence energy balance, insulin sensitivity, and inflammation
• Personalized nutrition approaches based on individual genetic variations (nutrigenomics) and metabolic responses (metabolomics) are being explored as potential strategies for optimizing macronutrient intake and disease prevention
  • Genetic polymorphisms in genes related to macronutrient metabolism (e.g., PPAR, FTO) may influence individual responses to dietary interventions
  • Integrating data from nutrigenomics, metabolomics, and the gut microbiome may enable the development of targeted, personalized nutrition recommendations in the future