Nutrients Sustaining Cells, Organs, and Health

Daniel S, L. Roberts, Ph.D.

Summary: All organ systems are composed of specialized cells that rely on specific nutrients to sustain metabolism and synthesize essential biomolecules necessary for energy production, tissue repair, and immune defense. To that end, adequate nutrient intake is required to support physiological resilience and reduces the risk of nutrient-deficiency–related disorders, including chronic physical diseases, cognitive decline, and emotional dysregulation.

Nevertheless, the increasing prevalence of ultra-processed foods and restrictive dietary patterns has become a significant driver of chronic disease. Ultra-processed foods often lack essential micronutrients while containing excessive amounts of refined carbohydrates, saturated fats, and sodium, which contribute to systemic inflammation and metabolic imbalance. In contrast, dietary patterns rich in minimally processed, nutrient-dense whole foods—providing adequate amounts of protein, dietary fiber, vitamins, minerals, and unsaturated fats—help fulfill the specific nutrient demands of cells and organ systems.

Importantly, when homeostatic balance is achieved, individuals typically experience stable energy levels, improved appetite regulation, healthy body weight, restorative sleep, and enhanced stress resilience. Cognitive functions—such as memory, attention, reasoning, problem-solving, decision-making, processing speed, creativity, and learning capacity—as well as emotional well-being, also improve under these optimal dietary conditions.

Interestingly, the healthiness of a diet (i.e., a balance intake of various food groups that provide all nutrients for optimal health). can be evaluated using validated tools such as the Healthy Eating Index (HEI) and the Alternative Healthy Eating Index (AHEI). Both indices consistently highlight the benefits of nutrient-dense, minimally processed dietary patterns—such as the Mediterranean diet and the Ai-driven all-nutrient diet—in promoting optimal organ function, genomic stability, and homeostatic balance.

Collectively, the evidence underscores that optimal health depends on maintaining a dynamic equilibrium between nutrient sufficiency and moderation. Both nutrient restriction and nutrient excess can impair cellular functions and accelerate the decline of cell-organ systems. In addition to dietary patterns, a range of additional factors—including physical and mental health status—can influence or exacerbate nutrient deficiencies.

Overall, long-term health and longevity depend on nutrient balanced diets to meet the body’s biochemical needs while minimizing ultra-processed foods. Personalized nutrition—integrating genetic, metabolic, and clinical data—allows for tailored dietary interventions. Combined with lifestyle factors such as stress management, regular exercise, sufficient sleep, and targeted supplementation, these practices help maintain metabolic balance, cellular integrity, and overall well-being across the lifespan.

e-Content

·         Nutrients supporting cellular functions and organ system health

·         Nutrients supportive of the digestive system and the genetic system

·         Nutrients supporting the immune system, and the brain and nervous system

·         Nutrient for heart and cardiovascular health and other organ systems

·         Nutrient deficiencies among animals

·         Geographical variations in nutrient access and health outcomes

·         Diet, cognition, and longevity. Nutritional pathways for healthy aging

·         Homeostasis: an indicator of health

·         Nutrient-restricted and nutrient-excess diets: Risks and implications

·         Healthy indices associated with specific diets + Comparative diet quality scores

·         Effects of medication on nutrient absorption and metabolism

·         Conclusion: Nutrient deficiencies and their broader health implications

Nutrients Supporting Cellular Functions and Organ System Health

The human body is composed of fourteen (14) interdependent organ systems, including the cardiovascular, genetic, immune, and reproductive systems. Each organ system is built upon four fundamental tissue types—epithelial, connective, muscle, and nervous tissue—that provide the structural and functional foundation for all organs. Collectively, these tissues and systems, composed of specialized cells, sustain life by orchestrating a wide range of physiological processes (Marieb & Hoehn, 2019).

Even though all cells share universal requirements, for energy and maintenance, the specific nutrients they depend upon vary according to their cellular function, metabolic activity, and structural composition (Stipanuk & Caudill, 2013). For example, the digestive system relies on adequate intake of dietary fiber, vitamins, zinc, and magnesium to regulate gastrointestinal health. In contrast, hepatocytes in the liver depend on B vitamins, antioxidants, and amino acids to perform tasks such as detoxification, energy production, and bile acid synthesis.

It is important to recall that specialized cells within organs carry out metabolic reactions that transform dietary nutrients into essential biomolecules, including hormones, neurotransmitters, immune proteins, and metabolic by-products such as urea and carbon dioxide. The efficiency and quality of these metabolic outputs is central for maintaining systemic homeostasis, which underlies optimal health. When nutrient intake is insufficient, metabolic processes deteriorate, compromising not only the health of individual cells but also the integrity of the organ systems they comprise (Stipanuk & Caudill, 2013).

The consequences of nutrient deficiencies are often systemic and cumulative. Insufficient nutrient and/or excessive nutrient intake weaken tissue structure, disrupt enzyme activity, and impair cell functions and intercellular communication. Over time, these deficits contribute to chronic inflammation, oxidative stress, and tissue degeneration, thereby elevating the risk of systemic diseases. For instance, deficiencies in antioxidant nutrients such as vitamin E, selenium, and glutathione precursors can intensify oxidative damage in high-demand organs such as the brain and heart.

So, to prevent or mitigate such adverse effects, targeted nutrient interventions are often necessary. For instance, omega-3 fatty acids have been shown to reduce neuro-inflammation and support membrane integrity in nervous tissue (Calder, 2017a). Likewise, nutrient-dense dietary protocols tailored to the metabolic demands of specific organ systems can strengthen cellular resilience, improve physiological efficiency, and lower the long-term risk of metabolic dysfunction associated with chronic nutrient insufficiency (Gómez-Pinilla, 2008; Lordan, Tsoupras & Zabetakis, 2018).

Nutrients Supportive of the Digestive System

All living organisms—including plants and animals—require nutrients to sustain life. In humans, this essential need is fulfilled by the digestive system. The digestive system consists of a network of organs responsible for breaking down food, absorbing nutrients, and eliminating waste. The process of digestion begins in the mouth, where mechanical and enzymatic processes are initiated, and then continues through the esophagus, stomach, small intestine, and large intestine (O’Keefe et al., 2015).

Each organ within the digestive system depends on a wide range of nutrients to maintain its structure, function, enzyme production, absorption, and microbiome balance. Key nutrients for structural and cellular integrity of digestive organs include vitamins A and D, zinc, the amino acid glutamine, and omega 3 fatty acids (Calder, 2017a). Enzymes needed for proper digestion encompass vitamin B1 (thiamine) and vitamins B2 (riboflavin), B3 (niacin), and B6 (pyridoxine), as well as chloride, and sodium (Stipanuk & Caudill, 2013).

Stomach acidity and nutrient absorption

Although most nutrient absorption occurs in the small intestine, effective digestion—particularly of proteins—requires sufficient stomach acid, primarily hydrochloric acid (HCl). Low stomach acid (hypochlorhydria) significantly impairs the absorption of calcium, iron, folic acid, vitamin B6, vitamin B12, and fat-soluble vitamins such as A and E (Allen, 2009). Symptoms of low stomach acid often resemble those of excessive acid production, including gastroesophageal reflux disease (GERD). Common symptoms include bloating, flatulence after meals and constipation. Low stomach acid has been associated with conditions including pernicious anemia, gastritis, diabetes mellitus, eczema, hepatitis, lupus erythematosus, and ulcerative colitis (Feldman et al, 2015).

A number of nutritional strategies help restore gastric function and improve nutrient absorption. These include consuming lean proteins to stimulate gastric secretions, selecting heme-iron sources, pairing non-heme iron with vitamin C, and prioritizing foods rich in vitamin B12. Adequate calcium, magnesium, and zinc can be obtained from dairy products, calcium-set tofu, nuts, seeds, and whole grains. Fermented foods and bitter greens may enhance digestion, while smaller, well-chewed meals and reducing alcohol or high-fat intake can help prevent postprandial discomfort (O’Keefe et al., 2015).

The gut microbiome and dietary fiber

The health of the digestive system—and indeed, many other organ systems—depends largely on the microbiome sustained by adequate dietary fiber intake. Although dietary fiber is not classified as a nutrient, it plays a vital role in maintaining stool bulk, regulating body weight, and promoting microbial equilibrium within the gastrointestinal tract. This process is carried out by the large intestine containing trillions of bacteria that contribute to digestion, nutrient metabolism, and immune defense. Prebiotic fibers act as substrates for beneficial gut microbes, which ferment these fibers into short-chain fatty acids (SCFAs) such as butyrate. These metabolites help preserve the integrity of colonic epithelial cells and exert potent anti-inflammatory effects (Koh et al., 2016).

In spite of its importance, fiber intake is inadequate in many populations. A United Kingdom study (Public Health England, 2018) found that only 9% of adults aged 19 to 64 consumed sufficient fiber. Inadequate intake contributes to dysbiosis, reducing the production of beneficial metabolites. Gut bacteria not only generate short-chain fatty acids (SCFAs) but also synthesize B vitamins, vitamin K, and neurotransmitters such as serotonin, dopamine, and acetylcholine. While these neurotransmitters cannot cross the blood–brain barrier, they influence the enteric nervous system, which contains approximately 500 million neurons, and communicate with the brain via the vagus nerve (Bourassa et al., 2016; Rao & Gershon, 2016).

The Genetic System: A Distributed, Self-Regulating Operating System

At its foundation, the genetic system relies on nucleic acids—primarily deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)—to encode, store, and communicate biological instructions. DNA preserves heritable information, while transcription copies segments of DNA into RNA. Translation then allows ribosomes to read messenger RNA (mRNA) and synthesize proteins. These proteins—enzymes, receptors, transporters, and structural components—collectively sustain essential cellular functions, including energy production, signaling, and repair (Lodish et al., 2021).

Within this framework, the genome functions as the “source code,” containing the complete set of genetic instructions that define an organism’s potential structure and function. Gene expression, in turn, represents the execution layer that converts informational sequences into tangible biological outcomes through the production of vital biological products. These products primarily include proteins—such as enzymes, receptors, transporters, and structural components—that perform essential cellular tasks.

Gene-encoded enzymes catalyze the conversion of dietary substrates into molecules required for cellular and organ function. The amino acid tryptophan, for instance, is enzymatically converted to serotonin, a process dependent on vitamin B6 as a cofactor (Roth et al, 2021). Similarly, tyrosine serves as a precursor for catecholamines (dopamine and norepinephrine) and thyroid hormones, with iron- and copper-dependent enzymes playing key roles. These examples illustrate how the genetic “software” dynamically integrates nutrient availability to generate functional outputs—neurotransmitters, hormones, membranes, and structural proteins—linking diet directly to cellular performance.

Nutrient–gene interactions and genomic stability

Numerous nutrients critical for circulatory and metabolic functions are essential to the proper functioning of genetic system. B-complex vitamins are critical for DNA synthesis and methylation, particularly folate and vitamin B12, which provide methyl donors through one-carbon metabolism (Crider et al., 2012; Anderson et al., 2012). Omega-3 fatty acids (e.g., EPA and DHA) influence gene regulation through nuclear receptors such as PPARs, thereby modulating metabolic and inflammatory pathways (Kolehmainen et al., 2012). And, coenzyme Q10, a vitamin-like compound, supports nuclear and epigenetic activity, as deficiencies and supplementation have been linked to altered gene expression and DNA methylation patterns (López-Lluch et al., 2010).

Moreover, minerals such as magnesium and phosphorus are indispensable for maintaining genomic stability and cellular metabolism. Magnesium serves as an enzyme cofactor in more than 300 biochemical reactions, including those involved in DNA replication, transcription, and repair (Hartwig, 2001). Phosphorus, by contrast, forms the structural framework of nucleic acids through the phosphate backbone of DNA and RNA and is equally vital in energy transfer reactions, forming high-energy phosphate bonds in ATP, GTP, and phosphocreatine (Lodish et al., 2021). Together, these minerals ensure the integrity of genetic material and the continuity of energy-dependent cellular functions essential for life.

Ultra-Processed foods and genetic stability

Nutrient-poor ultra-processed foods (UPFs) have been increasingly linked to DNA damage and epigenetic alterations, both of which disrupt normal gene function and compromise cellular regulation. These disruptions can impair cell and organ function contributing to chronic diseases such as cardiovascular disease, diabetes, and other metabolic disorders (Fardet, 2016; Pagliai et al., 2021). In other words, UPFs do not merely interfere with metabolism at the cellular or tissue level; they undermine the genetic and epigenetic mechanisms governing cellular function, division, and repair (Srour et al., 2019; Lane et al., 2021).

A meta-analysis of the epigenome-wide association studies (EWAS) in European children reported associations between UPF consumption and DNA methylation at seven CpG sites (Lauradó-Pont et al., 2025). Similarly, a study in the British Journal of Nutrition found that higher UPF intake was associated with increased oxidative DNA damage (Edalati et al., 2020). In Brazil, Vieira et al. (2024) observed that processed food consumption correlated with increased methylation of the NR3C1 gene promoter region. As NR3C1 encodes the glucocorticoid receptor, its hypermethylation has been associated with hypothalamic–pituitary–adrenal (HPA) axis dysregulation and heightened vulnerability to stress-related disorders.

Genetic Diversity and Dietary Requirements

Genetic diversity plays a crucial role in nutrient metabolism, shaping individual variations in dietary requirements and health outcomes. One of the most extensively studied examples involves the methylenetetrahydrofolate reductase (MTHFR) gene, which has been associated with elevated plasma homocysteine levels and an increased dependence on folate intake to sustain one-carbon metabolism (Frosst et al., 1995).

There are numerous genetic polymorphisms—defined as variations in DNA sequence— that affect how efficiently the body absorbs, transports, metabolizes, and utilizes all essential and non-essential nutrients such as vitamins, minerals, amino-acids, and fatty acids (Corella & Ordovás, 2018). These genetic differences contribute to marked inter=individual variability in nutrient requirements and responses to dietary interventions.

Recognizing the impact of genetic variability on nutrient metabolism underscores the growing importance of personalized nutrition—an approach that aligns dietary recommendations with an individual’s genetic, metabolic, and physiological profile. This precision-based strategy holds promise for optimizing nutrient status, enhancing physical, cognitive, and mental well-being, and reducing the risk of chronic diseases linked to nutritional imbalances (Ferguson, 2013; Simopoulos & Milner, 2010).

Nutrients for the Brain and Nervous System

The brain, often described as the body’s control center, regulates a wide range of functions, including cognition, emotion, sensory perception, and passive processes such as respiration and cardiac rhythm. These functions are executed through the broader nervous system that comprises the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS included the brain and spinal cord, while the PNS consists of an extensive network that relays signals between the brain, spinal cord, and all parts of the body (Kandel et al, 2021).

Key nutrients for the brain and nerve health

Nutrients have a fundamental role in maintaining the health and functionality of both the brain and the nervous system. The brain is composed of approximately 60% fat by dry weight, emphasizing its dependence on lipid-based molecules for optimal performance. Among these, docosahexaenoic acid (DHA)—a long-chain omega-3 polyunsaturated fatty acid—is the primary structural component of neuronal membranes. Along with eicosapentaenoic acid (EPA), DHA supports membrane fluidity, synaptic transmission, and neuroprotection. EPA exhibits strong anti-inflammatory properties that help regulate neuronal signaling and protect against chronic inflammation and neurodegenerative processes (Bazinet & Layé, 2014).

In addition to essential fatty acids, the brain also requires a wide spectrum of nutrients—vitamins, minerals, phytochemicals, polyphenols, and dietary fiber—to sustain energy metabolism, neurotransmitter synthesis, antioxidant defense, and cellular repair. These compounds influence the gut–brain axis, where metabolites from bacterial fermentation of plant-based polyphenols exert neuroprotective effects (Gómez-Pinilla, 2008).

B vitamins: Critical cofactors for neural function

Specific vitamins are indispensable for neural function. Vitamin B1 (thiamin) facilitates the conversion of glucose—the brain’s preferred energy source—into cellular energy. Vitamin B6 (pyridoxine) supports the synthesis of neurotransmitters such as serotonin and dopamine, which regulate mood, cognition, and motivation. Vitamin B12 (cobalamin) is crucial for maintaining the myelin sheath that insulates nerve fibers and for supporting red blood cell production (Kennedy, 2016).These vitamins are found in foods such as meat, fish, poultry, eggs, dairy products, beans, leafy greens, and fortified cereals.

Antioxidants: Defending the brain from oxidative stress

The brain’s high content of unsaturated fats—though vital for neural integrity—renders it particularly vulnerable to oxidative stress. These fats include monounsaturated fatty acids (oleic and palmitoleic acids) and polyunsaturated fatty acids such as alpha-linolenic acid (ALA), EPA, DHA, as well as omega-6 fatty acids like linoleic acid (LA) and arachidonic acid (AA). Over time, oxidation of these lipids can damage neuronal membranes, impair synaptic function, and accelerate cognitive decline.

Antioxidant nutrients—including vitamin C, vitamin E, and polyphenols found in foods such as berries, cocoa, green tea, beans, nuts and seeds—help neutralize free radicals (unstable molecules that can damage cells through oxidative reactions) and protect neuronal cells from oxidative injury. By mitigating oxidative stress, these compounds promote neuroplasticity, delay age-related neurodegeneration, and support long-term brain health.

Nutrients for Heart and Cardiovascular Health

The cardiovascular system—comprising the heart, blood vessels, and circulating blood—serves as the body’s primary transport network. It delivers oxygen and essential nutrients to tissues while removing carbon dioxide and metabolic waste. Beyond its transport role, the cardiovascular system is vital for maintaining homeostasis, regulating blood pressure, and supporting immune defense. Sustained cardiovascular health depends on a balanced supply of nutrients that preserve vascular integrity, maintain electrolyte equilibrium, and regulate lipid metabolism (Sacks et al., 2017).

Key Nutrients for Cardiovascular Health

Of particular interest, the sinoatrial (SA) node—the heart’s natural pacemaker—relies on a steady supply of nutrients to generate rhythmic electrical impulses. Electrolytes such as potassium, calcium, magnesium, and sodium are essential for maintaining the heart’s electrical activity and contractility. Deficiencies in these minerals can result in arrhythmias and impaired cardiac performance (Tangvoraphonkchai, & Davenport, 2018).

In addition, the SA node depends on nutrients that support mitochondrial energy production, including coenzyme Q10, the B-vitamin complex, and glucose. Antioxidants such as selenium and vitamins C and E also play a protective role by mitigating oxidative stress and preventing cellular damage in cardiac tissue. Insufficient intake of these nutrients can impair pacemaker function and increase the risk of atrial fibrillation or heart failure (Sharma et al., 2004).

Omega-3 fatty acids—especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—further contribute to cardiovascular health by reducing systemic inflammation, lowering triglyceride levels, and improving endothelial function (Calder, 2017a; Mozaffarian& Wu, 2011). Although the liver synthesizes most circulating cholesterol, dietary intake significantly influences lipid profiles. Foods rich in saturated fats, such as red meat, butter, full-fat dairy, and coconut oil, should be consumed in moderation in accordance with current dietary guidelines (Sacks et al., 2017).

In contrast, unsaturated fats—both monounsaturated and polyunsaturated—are associated with improved cardiovascular outcomes. Found in olive oil, avocados, nuts, seeds, and fatty fish, these healthy fats promote favorable cholesterol ratios and reduce the risk of cardiovascular disease (Mozaffarian et al., 2010). Observational and clinical research further supports that diets abundant in omega-3 fatty acids are linked to a lower incidence of atrial fibrillation and other cardiac events (Fitzgerald et al., 2014). When combined with adequate intake of essential micronutrients and antioxidants, such dietary patterns form the foundation of long-term heart health.

Integration with other organs systems

The organs described above function in concert with all other organ systems to maintain physiological equilibrium. In the appendix, Table 1 presents an overview of the fourteen human organ systems, outlining their primary organs and key physiological functions. Table 2 extends this overview by identifying the nutrients essential for each system’s optimal performance, as well as the common symptoms and diseases associated with specific nutrient deficiencies.

To explore this interdependence further, AI-assisted tools such as ChatGPT can generate detailed lists of all human organ systems, each accompanied by concise descriptions of their functions and nutritional requirements. These tools can also identify more than 200 types of cells comprising these systems, specifying the nutrients necessary for sustaining their metabolic and structural activities.

An effective prompt might be: " List the organs of the digestive system (or the genetic system), describe their functions, and identify the key nutrients required for optimal health. Include the diseases that may result from nutrient deficiencies and their respective treatment.”

Nutrient Deficiencies among Animals

As well, nutrient deficiencies in animals can profoundly affect their growth, reproduction, immune function, and overall health. Like humans, animals require a balanced intake of essential nutrients—including vitamins, minerals, amino acids, and fatty acids—to sustain normal physiological processes. When animals do not receive adequate amounts of these nutrients, whether due to poor-quality feed, environmental limitations, or health disorders that impair nutrient absorption, they may develop specific deficiency diseases.

For example, inadequate calcium and phosphorus intake can lead to weakened bones and disorders such as rickets in young animals or osteomalacia in adults. Similarly, vitamin A deficiency may impair vision, hinder growth, and weaken immune defenses, while insufficient essential fatty acids can cause poor coat quality and reproductive challenges (Goff, 2018; McDowell, 2003).

Let's note that the effects of nutrient deficiencies vary widely depending on the species, age, physiological state, and the particular nutrient involved. In livestock, such deficiencies can reduce productivity and cause significant economic losses. In wild animal populations, inadequate nutrition can compromise survival and reproductive success (Robbins, 2012).

Preventing and managing nutrient deficiencies requires carefully balanced diets, the use of fortified feeds, and, when necessary, targeted supplementation programs. Veterinary professionals and animal nutritionists routinely monitor dietary composition and health indicators to ensure that animals meet their nutritional requirements at every stage of life—particularly during periods of rapid growth, lactation, and recovery from illness (Goff, 2018; McDowell, 2003; National Research Council, 2007).

Geographical Variation in Nutrient Access and Health Outcomes

Allso, access to essential nutrients varies significantly across geographic regions, influencing population health and disease prevalence. Individuals living in certain areas of the world often lack consistent access to the full range of nutrients required for optimal health. In mountainous regions such as the Himalayas and the Andes, for example, populations experience high rates of anemia due to limited seafood consumption and soil deficient in iodine. In contrast, coastal communities that rely heavily on seafood may suffer from deficiencies in other micronutrients, including iron and calcium.

These nutrient imbalances have been linked to a range of health conditions, such as goiter, stunted growth, and iron-deficiency anemia—characterized by fatigue and impaired cognitive function—as well as night blindness, which heightens susceptibility to infections, particularly among children. Geographic and environmental factors, including restricted access to diverse food sources, soil nutrient depletion, and agricultural limitations, further exacerbate these nutritional disparities (Institute of Medicine, 2006).

Addressing the multi-factorial nature of nutrient deficiencies requires an integrated, evidence-based approach. Effective interventions include direct nutrient supplementation, fortification of staple foods with essential vitamins and minerals, and public education initiatives that promote dietary diversity and the consumption of whole, nutrient-dense foods. Collectively, these strategies are vital not only for treating existing deficiencies and malnutrition but also for preventing recurrence and promoting sustainable improvements in global health outcomes.

Diet, Cognition, and Longevity: Nutritional Pathways to Healthy Aging

Aging is accompanied by a series of physiological, metabolic, and cognitive changes that collectively influence health, independence, and quality of life. As metabolic rates slow, energy requirements typically decline, yet the need for essential nutrients remains constant—or even increases—to sustain tissue repair, immune defense, and neurological function. Bone density commonly decreases, predisposing older adults to osteoporosis, while a progressive loss of skeletal muscle mass and strength, known as sarcopenia, can impair mobility and functional capacity. Simultaneously, immune efficiency may decline, increasing susceptibility to infection and reducing vaccine responsiveness. The prevalence of chronic diseases—including type 2 diabetes, hypertension, and cardiovascular disorders—also rises with advancing age (Volkert et al., 2019).

Although biological aging is inevitable, individuals can influence the quality of aging through nutrition and lifestyle. Diets emphasizing all-nutrient-dense and whole foods—rich in vitamins, minerals, fiber, and unsaturated fats—help preserve physiological function and mitigate chronic disease risk. Adequate intake of calcium, vitamin D, magnesium, and protein supports bone and muscle integrity, while antioxidants such as vitamins C and E help neutralize reactive oxygen species that contribute to cellular aging (Ames, 2018).

Cognitive health is another crucial dimension of aging. Natural declines in memory, processing speed, and attention are common, yet the degree of cognitive impairment varies widely among individuals. Nutritional factors play a pivotal role in moderating these changes. Omega-3 fatty acids (especially DHA and EPA) contribute to neuronal membrane fluidity and synaptic signaling, while B vitamins—particularly folate, vitamin B6, and vitamin B12—facilitate one-carbon metabolism and maintain homocysteine balance, thereby protecting against neurodegeneration (Otaegui-Arrazola et al., 2014). In addition, polyphenols and other antioxidants found in fruits, vegetables, and teas help reduce oxidative stress and inflammation, processes strongly linked to cognitive decline.

Healthy aging and longevity extend beyond nutrition alone. An integrative approach—encompassing a balanced diet alongside key lifestyle factors such as regular physical activity, adequate sleep, effective stress management, and meaningful social connections—produces powerful, synergistic benefits. Adlso, mental engagement through activities like reading, problem-solving, and lifelong learning further enhances neuroplasticity and strengthens emotional resilience. Together, these elements work in harmony to preserve physical vitality, cognitive sharpness, and psychological well-being throughout the lifespan.

Homeostasis: An Indicator of Health and Well-Being

Homeostasis represents the body’s intrinsic ability to maintain a stable internal environment despite fluctuations in external or internal conditions. When organ cells receive adequate nutrients to support their specific metabolic processes, physiological equilibrium is more effectively sustained. This dynamic balance regulates critical parameters such as body temperature, pH, fluid volume, and energy availability, ensuring that cellular and organ functions proceed optimally. Under conditions of stable homeostasis, organs perform efficiently, tissues repair effectively, immune responses remain balanced, and energy metabolism adapts to meet changing physiological demands (Guyton & Hall, 2021).

Impairment of homeostatic balance and common symptoms

When homeostatic balance is disturbed, early manifestations are often subtle and nonspecific. Nutrient deficiencies can impair metabolic and neurological stability even before overt disease develops. For example, iron deficiency, even in the absence of anemia, has been associated with fatigue and diminished physical endurance. Clinical research indicates that iron repletion in deficient individuals can restore energy levels and improve exercise tolerance (Patterson et al., 2001). Similarly, vitamin B12 deficiency may lead to neuro-psychological symptoms such as cognitive decline, mood disturbances, and paresthesias, while iron insufficiency can reduce attention and concentration. Although such symptoms are not diagnostic in isolation, their presence should prompt further investigation into nutritional adequacy and metabolic balance (Allen, 2008).

Clinical monitoring and laboratory assessment of homeostasis

Routine clinical monitoring plays a vital role in detecting early disruptions in homeostasis and preventing progression to disease. Laboratory evaluations, ideally guided by a qualified clinician, provide objective measures of physiological stability. A complete blood count (CBC) is commonly used to identify hematologic abnormalities and potential nutrient deficiencies, including those related to iron, folate, and vitamin B12.

The complete blood count (CBC) is often complemented by a comprehensive metabolic panel (CMP), which assesses kidney and liver function through indicators such as creatinine, estimated glomerular filtration rate (eGFR), and liver enzyme levels. In addition, a lipid profile is typically conducted to evaluate cardiovascular and metabolic health, enabling clinicians to detect dyslipidemia and monitor responses to dietary and pharmacological interventions (Pagana, Pagana, & Pagana, 2021).

Collectively, these assessments provide a comprehensive snapshot of the body’s internal environment, enabling clinicians to detect deviations from homeostatic balance early and implement appropriate interventions. Sustaining biochemical and physiological equilibrium through targeted/personalized nutrition, regular monitoring, and timely correction of deficiencies is vital for promoting long-term health and overall well-being (Gibson, 2022).

Nutrient-Restricted and Nutrient-Excess Diets: Risks and Implications

A wide range of dietary patterns fall under nutrient-restricted and nutrient-excess (surplus) diets. These diets are often adopted for diverse reasons, including health optimization, athletic performance, weight management, or ethical and environmental motivations. While such approaches can yield short-term benefits, long-term, they can predispose individuals to nutrient deficiencies, toxicities, or metabolic imbalances, particularly when they diverge substantially from established Recommended Dietary Allowances (RDAs) for macro- and micronutrients (National Academies of Sciences, Engineering, and Medicine, 2019).

Importantly, nutrient-restricted and nutrient-excess diets can, in many cases, inadvertently exacerbate pre-existing conditions. Hence, personalized dietary assessment and periodic clinical monitoring are essential to ensure that nutrient intake remains within physiologically optimal ranges that support health, longevity, and homeostasis.

Nutrient-restricted diets

Nutrient-restricted diets limit one or more macronutrients or micronutrients. Examples of nutrient-restricted diets include carbohydrate-restricted diets, fat-restricted diets, protein- or amino-acid–restricted diets, potassium-restricted diets, and phosphorous-restricted diets.

Carbohydrate-restricted diets: The ketogenic diet (KD) restricts carbohydrate intake to approximately 20–50 g/day, inducing a metabolic state of ketosis in which the body relies primarily on fat for energy. This diet is used clinically for epilepsy management, weight reduction, and metabolic syndrome control (Kossoff et al., 2018). Similarly, low-carbohydrate diets (<130 g/day) increase protein or fat intake to improve glycemic control in individuals with type 2 diabetes (Feinman et al., 2015). A phased variation, the Atkins diet, gradually reintroduces carbohydrates gradually following an initial ketogenic phase.

Fat-restricted diets: The very-low-fat diet limits fat to ≤15% of total caloric intake and is exemplified by the Ornish diet, which emphasizes fruits, vegetables, legumes, and whole grains (Ornish et al., 1998). While effective for reducing serum cholesterol, excessive fat restriction may impair the absorption of fat-soluble vitamins (A, D, E, and K).

Protein-restricted diets: The low-protein diet, typically 0.6–0.8 g/kg/day, is used to reduce nitrogen load in patients with chronic kidney disease (CKD) (Kopple, Massry, Kalantar-Zadeth & Fouque, 2021). Another example is the phenylalanine-restricted diet, which is medically necessary in phenylketonuria (PKU) to prevent the neurotoxic accumulation of phenylalanine (Vockley et al., 2014).

Although each of these dietary approaches serves a clinical or metabolic purpose, long-term adherence without professional supervision can result in deficiencies of key nutrients such as B vitamins, essential fatty acids, amino acids, and trace minerals, leading to systemic dysfunctions.

Nutrient-excess diets or surplus nutrient diets

At the opposite end of the spectrum are nutrient-excess diets, which provide nutrients well above the body’s physiological requirements. These may be pursued for performance enhancement, bodybuilding, or longevity optimization, but excessive intake can lead to oxidative stress, electrolyte imbalance, and organ toxicity (Mocchegiani et al., 2012).

Examples include high-protein diets (>2.0 g/kg/day), high-calorie diets designed for weight gain, and megavitamin or orthomolecular diets that deliver nutrients at several times the recommended dietary allowance (RDA). Chronic over-consumption of certain nutrients, particularly fat-soluble vitamins or minerals like iron and selenium, may induce toxicity or increase the risk of chronic diseases.

Nutrient-optimized or functional diets

Beyond the restrictive–excess dichotomy lies nutrient-optimized or functional diets, which focus on enhancing biological performance rather than simply meeting or exceeding baseline nutrient needs. These diets are personalized to individual genetic, metabolic, and microbiome profiles, reflecting the principles of nutrigenomics (Corella & Ordovás, 2009).

Example of nutrient-optimized or functional diets include the anti-inflammatory diet, rich in omega-3s, antioxidants, and phytonutrients, reduces chronic inflammation and oxidative stress (Calder, 2017a); and the whole-food, plant-forward diets, high in fiber and antioxidants, promote metabolic health and favorable epigenetic modifications.

Nutrient-fortified and supplement-supported diets

In some contexts, the counterpoint to nutrient restriction is nutrient fortification or supplementation, aimed at preventing deficiencies or compensating for limited dietary diversity. Fortified foods and supplements are especially important in populations at risk of malnutrition or those living in regions with limited sunlight.

Examples include fortified cereals enriched with iron, folate, and vitamin B12 to prevent anemia; Vitamin D and calcium supplementation to support bone health in individuals with limited sun exposure, and Omega-3 or antioxidant fortification to improve cardiovascular and metabolic health outcomes. Although fortification can prevent deficiency, overuse of supplements may result in nutrient imbalance or competitive inhibition among micronutrients, underscoring the need for moderation and clinical monitoring.

Overall, nutrient-restricted and nutrient-excess diets underscore the delicate balance required for maintaining optimal human nutrition. While targeted restriction can yield therapeutic benefits, and nutrient surplus can enhance specific physiological domains, both extremes carry inherent risks. The emerging field of functional and nutrient-optimized nutrition offers a balanced paradigm—one that emphasizes personalized adequacy, metabolic harmony, and long-term health resilience.

Healthy Indices Associated with Specific Diets

Diets are likely the most influential determinants of overall well-being, affecting all aspects of one's health: physical, mental, emotional, and cognitive functioning. Of interest is that the quality of a person’s diet can be evaluated using composite indices that summarize nutritional adequacy and dietary balance. Among these, the Mediterranean diet and the AI-driven all-nutrient diet consistently achieve some of the highest scores for promoting optimal health and longevity.

An all-nutrient dietary pattern, which emphasizes diverse, minimally processed foods that collectively provide both essential and non-essential nutrients, performs exceptionally well on established measures of diet quality—such as the Healthy Eating Index (HEI), and the Alternative Healthy Eating Index (AHEI). Higher scores on these indices are consistently associated with better overall health outcomes, reduced risk of chronic disease, and lower all-cause mortality. Definitions of the HEI and AHEI are as follows:

·           Healthy Eating Index (HEI): The HEI assesses diet quality based on 13 components, including fruit, vegetable, whole-grain, seafood, and plant-protein intake, as well as moderation components such as added sugars, saturated fat, and sodium. Each component is scored and summed for a total score ranging from 0 to 100, with higher scores indicating greater alignment with dietary guidelines and better overall diet quality.

·           Alternative Healthy Eating Index (AHEI): The AHEI evaluates intake of 11 food and nutrient components known to influence chronic disease risk, including vegetables, fruits, whole grains, nuts, legumes, omega-3 fatty acids, polyunsaturated fats, red and processed meats, sugar-sweetened beverages, trans fats, sodium, and alcohol. Scores range from 0 to 110, with higher values predicting a lower risk of major diseases and mortality.

The table below presents a comparative overview of diet quality and health index scores for several popular dietary patterns, based on findings from peer-reviewed studies. These values serve as approximate benchmarks and should be interpreted with caution, as results vary depending on the study population, scoring methodology, and data collection procedures.

Comparative Diet Quality Scores of Popular Diets (HEI and AHEI)

Altogether, the AI-driven all-nutrient diet achieves the highest score with established dietary indices, reflecting comprehensive nutrient adequacy and homeostatic support. Among the empirically observed diets, the Mediterranean and pescatarian patterns achieve the second highest HEI and AHEI scores. The omnivore, paleo, keto, and especially ultra-processed food–based diets rank considerably lower due to nutrient imbalance and limited plant diversity.

The reader may query ChatGPT about other major diet quality and nutrient adequacy indices—beyond HEI and AHEI—that are used in nutritional science and epidemiology to evaluate overall diet quality, nutrient density, metabolic health, and inflammation. For instance, the Mean Adequacy Ratio (MAR) and Nutrient Adequacy Ratio (NAR), which evaluate the adequacy of nutrient intake relative to RDAs for multiple nutrients, and the Healthy Food Diversity (HFD) Index that measures dietary diversity and the distribution of food group consumption, based on Shannon’s entropy formula.

The Health Quotient (HQ) and Broader Determinants of Health

Other indicators of nutrition-related well-being include the Health Quotient (HQ), a multidimensional construct frequently examined in conjunction with the concept of biological age. The HQ represents an integrative framework that synthesizes multiple dimensions of health, combining an individual’s diet quality index with broader determinants such as educational attainment, socioeconomic status, and  lifestyle behaviors. By integrating these factors, the HQ reflects not only nutritional adequacy but also the social and environmental contexts that shape long-term health outcomes.

An individual’s biological age refers to their physiological and functional condition relative to chronological age, providing insight into how efficiently the body and cells are aging. Unlike chronological age, which merely counts the passage of time, biological age captures the cumulative impact of nutrition along with a host of measures, including, physical activity, metabolic efficiency, psychosocial and genetic variables on the rate of aging.

Together, the HQ and biological age offer a comprehensive, multidimensional assessment of well-being. This holistic framework extends beyond conventional bio-metric markers—such as body mass index or serum cholesterol—to encompass the complex interplay among nutrition, psychosocial resilience, and lifestyle factors. Consequently, the HQ serves as both a population-level and individualized tool for assessing health status, guiding preventive nutrition strategies, and informing personalized interventions that optimize longevity, vitality, and quality of life.

Effects of Medication on Nutrient Absorption and Metabolism

A lifelong diet dominated by ultra-processed foods or other nutritionally poor eating patterns—such as low-nutrient crash diets or those high in saturated and trans fats—is associated with the premature onset of chronic diseases, and increased risk of mental disorders. Although prescribed medications are most often effective and beneficial in managing these conditions, they can also interfere with nutrient absorption, metabolism, or utilization, thereby exacerbating existing nutritional imbalances.

Certain classes of medications are specifically designed to mimic or compensate for the biochemical functions of natural nutrients. These agents, broadly known as nutraceuticals or nutrient analogs, act within metabolic pathways or receptor sites to sustain physiological function. For example, mecobalamin, an active form of vitamin B12, promotes nerve regeneration by substituting for its natural counterpart in enzymatic reactions that support DNA synthesis and cellular repair.

Medications that modulate hormonal and enzymatic pathways

A second major category of pharmaceuticals includes drugs that act on hormonal or enzymatic pathways to restore physiological balance. Unlike nutrient analogs, which mimic or replace specific nutrients, these medications target precise biochemical mechanisms to correct dysregulation within the metabolic or endocrine systems.

For instance, angiotensin-converting enzyme (ACE) inhibitors such as lisinopril reduce blood pressure by inhibiting the angiotensin-converting enzyme, thereby lowering angiotensin II production and promoting vasodilation. Statins (e.g., rosuvastatin) suppress HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis, leading to decreased circulating cholesterol concentrations. Metformin, a first-line agent for type 2 diabetes, regulates hepatic gluconeogenesis and improves insulin sensitivity by modulating AMP-activated protein kinase (AMPK) pathways.

Collectively, these pharmacological interventions play a vital role in the management of chronic metabolic and cardiovascular disorders by re-establishing hormonal and enzymatic equilibrium. Through the targeted modulation of biochemical pathways, these medications help stabilize key physiological parameters—such as blood pressure, glucose homeostasis, and lipid concentrations—thereby preventing organ damage and improving long-term outcomes.

Medications that deplete or disrupt nutrient balance

In spite of their therapeutic benefits, many pharmaceuticals adversely affect nutrient status through mechanisms that impair absorption, storage, transport, metabolism, or excretion. As such, sustained pharmacotherapy often necessitates concurrent nutritional support, as some medications may alter nutrient absorption or metabolism, leading to secondary deficiencies(Goodman et al., 2021; Stipanuk & Caudill, 2022).

Synjardy, for example, a combination of empagliflozin and metformin used to manage type 2 diabetes, can alter vitamin and lipid metabolism. Metformin is known to reduce vitamin B12 absorption, potentially leading to deficiencies that impair nerve health and DNA synthesis. And, empagliflozin may elevate serum campesterol, a marker of cholesterol absorption, possibly contributing to increases in high-density lipoprotein (HDL) cholesterol (Jojima et al., 2021).

It is worth remembering that both components of Synjardy can also cause dehydration by increasing urinary glucose and water excretion, which may lead to hypotension, dizziness, or fainting. Because water is a universal nutrient vital to every cell, maintaining adequate hydration is essential for cardiovascular stability and systemic health.

Another illustrative example is Entresto, a dual-acting medication composed of sacubitril and valsartan used to manage chronic heart failure. Sacubitril has been shown to deplete essential micronutrients such as vitamins B1, B12, and D, as well as folate, iron, calcium, magnesium, selenium, and zinc. Valsartan, an angiotensin receptor blocker (ARB), can further reduce serum concentrations of magnesium, potassium, and zinc. Entresto may interact with potassium-rich foods or salt substitutes—such as bananas or low-sodium seasoning products—raising the risk of hyperkalemia, a potentially dangerous elevation of blood potassium that can impair cardiac rhythm.

Nutrient–drug interactions and clinical monitoring

Given these potential nutrient–drug interactions, sustained pharmacotherapy often necessitates concurrent nutritional support, as some medications may alter nutrient absorption or metabolism, leading to secondary deficiencies. Physicians may advise patients to avoid specific foods, increase their intake of nutrient-dense alternatives, or use supplements to maintain adequate blood nutrient levels (Higdon & Drake, 2022). Routine laboratory assessments—such as comprehensive metabolic panels or micronutrient assays—can help identify and manage drug-induced nutrient deficiencies before they lead to adverse health outcomes (Hendler & Rorvik, 2001; Gröber et al., 2015).

Conclusion: Nutrient Deficiencies and their Broader Health Implications

The growing prevalence of ultra-processed dietary patterns underscores the profound impact of nutrient imbalances and deficiencies on human health. Diets dominated by refined carbohydrates, added sugars, saturated fats, and sodium disrupt nutritional equilibrium by supplying excessive caloric energy while failing to provide essential micronutrients. Over time, these imbalances and nutrient deficiencies compromise metabolic homeostasis, weaken immune defenses, and elevate the risk of chronic cardiometabolic, neurodegenerative, and inflammatory disorders.

Both restrictive and excessive nutrient diets—often adopted for weight management, athletic enhancement, or therapeutic aims—can destabilize cellular metabolism. Macronutrient restriction, as observed in very-low-carbohydrate, very-low-fat, or calorie-restricted regimens, deprives the body of the vitamins, minerals, and cofactors required for enzymatic activity and cellular repair. Conversely, chronic over-consumption of certain nutrients, such as fat-soluble vitamins and trace minerals, may provoke oxidative stress, inflammation, and organ toxicity. Whether through deficiency or excess, loss of nutritional equilibrium undermines physiological resilience and frequently manifests as early fatigue, muscle weakness, cognitive decline, or emotional dysregulation.

Beyond dietary composition, a wide spectrum of biological, clinical, and psychosocial variables influences nutrient status. Chronic gastrointestinal disorders, liver or kidney dysfunction, persistent inflammation, and infections may impede nutrient absorption and metabolism. Genetic polymorphisms further modulate nutrient utilization by altering enzymatic activity, transport, or cofactor activation, thereby shaping individualized nutritional requirements. Moreover, psychological stress and behavioral patterns, including anxiety, depression, and poor sleep quality, elevate cortisol and catecholamine levels—accelerating nutrient turnover and increasing demands for magnesium, vitamin C, and B-complex vitamins.

Consequently, addressing nutrient deficiencies may require a personalized, multidimensional approach that integrates each individual’s dietary patterns, medical history, genetic makeup, metabolic profile, and psychosocial context. Nutritional screening and laboratory assessments are to be complemented by genomic and clinical data to tailor precise dietary interventions. Personalized nutrition planning—grounded in evidence-based recommendations—enables the optimization of nutrient intake to meet the body’s specific biochemical and physiological needs.

Ultimately, lifelong health and longevity are best sustained through balanced, minimally processed, all-nutrient-dense diets combined with personalized nutritional monitoring and holistic lifestyle management. Routine nutritional assessments, targeted supplementation when clinically indicated, effective stress regulation, regular physical activity, restorative sleep, and a reduction in ultra-processed food consumption collectively reinforce metabolic balance, preserve cellular integrity, and promote cognitive, emotional, and physical vitality throughout the lifespan.

APPENDIX: Summary of Nutrients Supporting the Body’s Organ Systems and Cells

Table1: The 14 human organ systems, their main organs, and functions:

Table 2: Nutrient Deficiency, Symptoms, and Diseases by Organ System

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