Definition/Introduction
Nutrition profoundly impacts health status across all stages of life, and unhealthy dietary habits represent one of the most important causes of disability and premature death.[1][2] While an optimal diet is essential for maximizing health and longevity, what constitutes an optimal diet remains controversial. Macronutrient intake is one of the most important aspects of any diet because of its significant and direct influence on energy balance, body composition, and health outcomes.[3][4][5]
Nutrients are essential compounds required to sustain physiological processes and are classified into two broad categories: macronutrients and micronutrients.[3][6][7] Macronutrients are compounds required in large amounts that play a critical role in energy provision, synthesis of structural molecules, hormone production, and regulation of metabolic pathways. Micronutrients, such as vitamins, minerals, and antioxidants, are essential compounds needed in smaller amounts for biochemical processes such as the modulation of gene transcription, catalyzing enzymatic reactions, and protection against oxidative stress.[7][8]
The three macronutrients are proteins, carbohydrates, and lipids. Alcohol is sometimes included as the fourth macronutrient, but its overall consumption is strongly discouraged, and it is not recommended as an energy source under any circumstances.[5] All macronutrients are considered sources of energy, but each one has unique biochemical properties and different effects on body composition and health.[4][5]
Proteins
Proteins are large molecules comprising varying amounts and combinations of amino acids linked via peptide bonds.[3][9] Although dietary proteins contain 4 kcal of energy per gram, they are considered a less efficient energy source than lipids or carbohydrates.[5][7] Rather, the most important function of dietary proteins is to supply amino acids, which provide nitrogen, hydrocarbon skeletons, and sulfur.[3][9] In the human body, amino acids are used for mechanical and structural purposes and help synthesize enzymes, hormones, antibodies, cytokines, transporters, and neurotransmitters. The ingestion of dietary protein increases amino acid availability, stimulates protein synthesis, inhibits protein catabolism, and helps regulate whole-body protein balance.[7][9]
Carbohydrates
Carbohydrates are an important dietary energy source and provide 4 kcal of energy per gram.[6][7] Carbohydrate intake raises blood glucose levels and stimulates insulin secretion, promoting glucose uptake into tissues and glucose storage as glycogen.[10] Additionally, carbohydrates play an important role in gut health and immune function. Fiber, a type of nondigestible carbohydrate with multiple subtypes, is important in promoting satiety, improving gastrointestinal function, and reducing cholesterol levels.[3][7]
Lipids
Lipids or dietary fats are the most energy-dense macronutrient and provide 9 kcal of energy per gram. [7] In human physiology, lipids are essential for the production of sex hormones, maintenance of cellular structure, energy storage as body fat, regulation of body temperature, protection from physical trauma, and the absorption of fat-soluble vitamins A, D, E, and K. Additionally, fats enhance the taste, texture, and palatability of foods.[11][12]
Dietary fats can be separated into triglycerides (fats and oils), phospholipids, sterols (cholesterol), and fatty acids. Fatty acids in the diet can be further distinguished according to the presence of double bonds; saturated fats have no double bonds, and unsaturated fats have one or more double bonds.[11] Finally, unsaturated fatty acids can be distinguished by the position of the first double bond counted from the methyl end of the carbon chain into omega-3, omega-6, and omega-9 fatty acids, with the first double bond occurring at the third, sixth, and ninth position, respectively. Different groups of dietary lipids have been known to have distinct physiological properties and health effects.[11]
Issues of Concern
Excessive or deficient macronutrient intake is associated with adverse health outcomes in the general population and may originate from inadequate consumption of an individual macronutrient or an overall excessive or deficient energy intake.
Macronutrient Deficiencies
Sufficient protein intake is essential for health and well-being at all ages. In children, adequate protein intake is essential for growth and development.[13] In adults, adequate protein intake helps maintain lean body mass and prevent age-related loss of skeletal muscle mass.[3] Nevertheless, protein undernutrition is common in developed and developing countries. Worldwide estimates suggest that over 1 billion people have chronically insufficient protein intake, with up to 30% of the children in central Africa and South Asia and over 50% of the homebound elderly population in the United States being affected. [9]
The repercussions of protein malnutrition range from mild to life-threatening, depending on individual characteristics, the degree of deficiency, and the presence of exacerbating factors such as concurrent illness and insufficient energy intake. Consequences of protein deficiency can be unspecific and include stunting, anemia, intrauterine growth restriction, impaired nutrient absorption, cardiovascular dysfunction, muscle wasting, immunodeficiency, hypoalbuminemia, edema, loss of bone mass, skin atrophy, and impaired hormone production, particularly of growth and thyroid hormones and insulin.[9]
Classical forms of protein deficiency include marasmus, a protein-calorie deficiency, and kwashiorkor, a protein deficiency within an energy-sufficient diet. Marasmus is characterized by dry and wrinkled skin, extreme muscle wasting, loss of subcutaneous fat, and atrophy of internal organs with preserved histology. Kwashiorkor is characterized by severe edema that is more pronounced in the hands and feet, wasting, diarrhea, irritability, skin depigmentation, fatty liver, and organ dysfunction. While these conditions are usually described as distinct entities, there is significant clinical overlap, and many patients exhibit features of both conditions, termed marasmic-kwashiorkor.[6][14] Laboratory assessments can help distinguish between these conditions; kwashiorkor presents with more pronounced and severe decreases in transferrin, albumin, and total plasma proteins, resulting from more profound impairments in protein synthesis.[14]
Unlike protein deficiency, which is common in the general population, lipid and carbohydrate deficiencies are extremely rare. However, a low intake of lipids or carbohydrates can have important implications for health and disease.[15][16]
Strictly speaking, carbohydrates are not considered essential nutrients because the body can synthesize carbohydrates endogenously and use alternative energy sources. Moreover, the absence of dietary carbohydrates does not result in a characteristic deficiency. However, nutrient-dense sources of carbohydrates, such as whole grains, fruits, and vegetables, contain nutrients and bioactive compounds associated with many health benefits and are unavailable in other food sources.[3][15] For this reason, nutrient-dense forms of carbohydrates are included in dietary guidelines.
The human body can also endogenously synthesize various forms of lipids. However, in contrast to carbohydrates, lipids are an essential macronutrient. They must be sufficient in the diet to provide essential fatty acids and allow for the absorption of fat-soluble vitamins.[17] Essential fatty acids include alpha-linolenic acid (omega-3) and linoleic acid (omega-6).[18] Essential fatty acid deficiency is rare in individuals with a regular diet and most frequently presents in individuals with severe fat malabsorption or fat-free parenteral nutrition. Findings suggestive of essential fatty acid deficiency include dermatitis, alopecia, liver dysfunction due to mitochondrial dysfunction, and increased susceptibility to infections. [19]
Excess Macronutrient Intake
While macronutrients are not directly toxic, even when consumed in large amounts, chronic macronutrient overconsumption can be a cause for concern. Chronic excess energy intake from carbohydrates and fats has been associated with weight gain, obesity, type 2 diabetes, hypertension, and other adverse health outcomes associated with increased adiposity.[20][21] Interestingly, overfeeding on protein alone is not associated with increased adiposity and has been shown to improve body composition, especially in individuals who engage in resistance exercise.[22] For this reason, the main concern of excess macronutrient intake is excess calorie intake and the consequences of increased weight and adiposity. However, excess consumption of a single macronutrient in a calorie-appropriate diet implies that another macronutrient is being displaced to remain within calorie limits. If chronic, this practice can also result in nutrient deficiencies.
There has been considerable debate concerning the safety of high-protein diets, with particular attention to kidney function. Some authors have proposed that high-protein diets may lead to kidney damage and disease. This concern was initially proposed after scientists discovered that high-protein diets cause a compensatory increase in the glomerular filtration rate (GFR), originally thought to result from nephron loss.[23] However, this increased GFR is a normal adaptation to increase solute clearance, and more importantly, high-protein diets are not a risk factor for developing chronic kidney disease in otherwise healthy individuals.[23]
Recommended Intakes
Macronutrient requirements can vary widely between individuals depending on several factors such as age, body weight, physical activity levels, and associated medical conditions. In general, recommendations for macronutrient intake and distribution provide a great deal of flexibility. Provided that essential macronutrient and micronutrient needs are covered and appropriate calorie numbers are consumed, macronutrient distribution may be adapted to fit individual preferences and goals.
Adequate protein intake is key in preventing age-related loss of muscle strength and muscle mass (sarcopenia).[24][25] The current recommended daily allowance (RDA) of protein for healthy adults is 0.8 g/kg and represents the average daily intake required to meet the minimal protein requirements and maintain nitrogen balance in 97.5% of the population. In other words, the RDA is the minimal amount needed to prevent a deficiency in most people.[9][13] For this reason, the RDA has been heavily criticized in recent decades; more recent studies demonstrate methodological pitfalls within the nitrogen-balance method on which the RDA is based, and a growing amount of evidence reveals better outcomes when protein intake exceeds the RDA.[24] Healthcare professionals must understand that the RDA reflects a minimal rather than an optimal protein intake.
While an optimal lower limit for protein intake has not been established, some authors have reported significantly lower age-related decreases in skeletal muscle with a daily protein intake of 1.2 g/kg. [25] An upper tolerable limit for protein intake has yet to be established. However, studies have shown that healthy adults can tolerate a long-term daily intake of 2 g/kg or more.[9] As a percentage of daily calories, the acceptable macronutrient distribution range (AMDR) for protein has been set at 10% to 35% for adults.[26] Yet, caution must be taken when calculating protein requirements as a percentage of daily calories; dietary protein serves mainly as a source of amino acids rather than a source of energy, and percentage-based calculations can yield inadequate numbers in individuals with lower- or higher-than-average calorie requirements.[5]
For example, 10% of daily energy requirements would equate to 120 kcal or 30 g of protein for a person on a 1200-kilocalorie diet, resulting in an insufficient intake. For an athlete with a 4000-kilocalorie diet, where 35% of daily energy would equal 1400 kcal or 350 g of protein, this amount could be more than necessary for amino acid requirements and result in displacing calories otherwise allocated to better energy sources, such as lipids or carbohydrates.
Unlike protein, dietary recommendations for carbohydrates and lipids are more flexible.[17] Current guidelines recommend a fat intake between 20% to 35% of daily calories to ensure adequate levels of essential fatty acids and fat-soluble vitamins.[16][26] Additional recommendations include limiting saturated fats to <10% of daily calories to reduce cardiovascular risk.[6] For carbohydrates, the AMDR has been set at 45 % to 65% of daily calories, with a limit of 10% of daily calories coming from added sugars.[27][28]
Obesity and Weight Loss
With obesity rates on the rise, efforts have been made to characterize the role of macronutrient intake in promoting weight gain and facilitating weight loss. Historically, carbohydrates and fats have been theorized to be responsible for the rising prevalence of obesity, and low-carbohydrate and low-fat diets have been proposed as promising solutions.[29][30][31] However, neither carbohydrates nor fats are inherently fattening, and their restriction has not been proven differentially superior in promoting weight loss.[32] Additionally, it is important to distinguish between different sources of each macronutrient, as processed versions are related to weight gain and obesity, while unprocessed versions are not. [33]
Because obesity is a complex condition that stems from excess total energy intake rather than any individual macronutrient, focusing interventions on macronutrient restriction is unlikely to be effective. Moreover, studies have shown that public health interventions aiming to reduce sugar intake can result in a paradoxical increase in fat consumption.[31] When considering weight loss outcomes, low-fat and low-carbohydrate diets are equally effective, similar to other dietary patterns that result in caloric restriction without eliminating specific food groups.[29][32]
Special Populations
A multitude of conditions and situations can influence nutritional requirements. In the case of macronutrient intake, special consideration is warranted at certain life stages and for people with certain medical conditions. Such scenarios include childhood, pregnancy, athletes, and people with specific medical conditions like chronic kidney disease or liver disease.
Due to the metabolic demands of growth and development, children and adolescents have higher relative energy and protein requirements than adults.[25] Children between 1 and 3 years old have the largest protein requirement in grams per kilogram because this period has the fastest growth trajectory.[34] Generally, protein requirements are estimated to be 20% to 60% greater in children and adolescents than in healthy adults.[25] Older adults are thought to require larger amounts of protein due to age-related changes in protein metabolism, such as anabolic resistance, insulin resistance, and decreased insulin growth factor-1 (IGF-1) levels, which result in lower muscle protein synthesis and increased protein breakdown.[24]
Pregnancy and lactation greatly increase metabolic demands for energy and protein to cover the needs of the gravida while supporting fetal development.[34][35] These demands increase gradually each trimester and, if not met, may result in adverse maternal and fetal outcomes.
In the context of disease, protein intake is important in managing various conditions, such as chronic kidney disease (CKD) and chronic liver disease (CLD). In patients with CKD, protein intake must be carefully balanced to prevent malnutrition while delaying disease progression.[36] Protein restriction may help prevent or slow disease progression but risks worsening the sarcopenia associated with CKD, which is associated with increased mortality in this population. Protein restriction may be warranted in patients with a high risk of progression to end-stage kidney disease, while low-risk patients may benefit from a higher protein intake.[36] In the setting of liver disease, protein restriction was previously recommended to reduce ammonia levels and improve symptoms of hepatic encephalopathy in patients with CLD. However, studies have shown that protein restriction in patients with CLD compromises their nutritional status and results in worse outcomes than normal-protein diets. For this reason, current guidelines do not recommend protein restriction.[37]
While healthcare professionals need to know about these special situations and their influence on nutrient requirements, patients with special requirements should be referred to a specialist for optimal and timely nutritional management.
Food Quality and Nutrient Sources
Meeting nutrient requirements is essential at all stages of life. However, promoting a holistic perspective that ensures nutritional adequacy through a whole-food approach is imperative.[25] Studies have consistently shown that the effects of foodstuffs go beyond the sum of individual nutrients and depend on the food matrix, which refers to the interaction of the physical structure and composition of food, involving both nutrient and non-nutrient components.[25][38] Macronutrient requirements should be met through nutrient-dense whole foods to promote health and reduce disease risk.
Healthy sources of carbohydrates include legumes, whole grains, fruits, and vegetables.[3] Unlike processed grains, from which the germ and bran have been removed, whole grains are high in fiber and micronutrients and have been associated with decreased risk of cardiovascular disease, cancer, diabetes, and all-cause mortality.[3] Similarly, fruit and vegetable intake is inversely correlated with chronic noncommunicable diseases, including hypertension, cardiovascular disease, metabolic syndrome, and lung cancer.[3] While the reasons behind these health effects are not yet completely understood, it is likely related to the phytochemicals and bioactive compounds present in the food matrix of such foods.[3]
Dietary proteins can be found in both plant-based and animal-based food sources.[24] Plant-based sources of dietary proteins include legumes, soy products, grains, nuts, and seeds. Animal-based sources of protein include meat, dairy, fish, and eggs.[24][3] Generally, animal-based foods are labeled as complete proteins because they contain all the essential amino acids humans require. An essential amino acid cannot be synthesized endogenously and must be obtained through the diet. In contrast, plant-based foods tend to be labeled as incomplete proteins due to the frequent lack of one or more essential amino acids. However, it is important to note that protein and essential amino acid needs can be met through plant-based sources by combining various food sources with different amino acid profiles, which offsets the lack of an essential amino acid in a given food source.[24][25] Moreover, certain processing techniques can increase the digestibility of plant-based proteins to induce a more robust muscle protein synthesis response.[39] A recent clinical trial showed that a high plant-based protein diet supplemented with soy powder was equally effective in increasing muscle mass as an omnivorous high-protein diet supplemented with whey protein, which supports the idea that once a protein threshold is achieved, the qualitative amino acid difference between types of protein becomes of less importance.[40]
Dietary fats can be obtained from various sources and are classified as monounsaturated, polyunsaturated, saturated, and trans-unsaturated fats.[3] Foods usually contain a combination of different types of fats. Unsaturated fats can be found in fish, plant oils, nuts, and seeds. Saturated fats are more common in animal foodstuffs, and trans-unsaturated fats are found in processed vegetable oils. Unsaturated fats are associated with decreased cardiovascular risk and mortality, while trans-unsaturated and saturated fats are associated with adverse effects on health.[3] For this reason, care must be taken with dietary fat and animal protein sources to stay within the recommended saturated fat intake of less than 10% of daily calories.[6]
Nutrition: Macronutrient Intake, Imbalances, and Interventions