The Role of Nutrition in Human Health Outcomes Beyond Energy Balance: A Biochemical and Physiological Perspective on Essential Nutrients

Part two in my five-part series covering what I call "The Five Pillars of Metabolic Health"

Human beings are physiologically adapted to a hypercarnivorous diet, reflecting an evolutionary history focused on nutrient-dense, animal-based foods (Geissler and Powers, 2017). This dietary adaptation emphasized protein and fat as not only the primary energy and sources, but also the primary nutrient sources too, and this is important because nutrition is far more complex than merely the provision of energy.

You see, our nutrition is not just for ATP synthesis but also for supporting complex biochemical and physiological processes across bodily systems. Nutrition plays a critical role in health outcomes beyond energy balance by providing the essential amino acids, fatty acids, vitamins, and minerals necessary for cellular function, tissue repair, and systemic regulation (Gropper et al., 2018).

This essay examines the essential nutrients required for human health and explores their roles across the body’s major physiological systems, highlighting their significance within an energy-intensive, nutrient-specific hypercarnivorous framework.

A. Energy Balance in Terms of ATP Production:

Energy balance in human physiology is maintained by the production of ATP, the cellular “energy currency,” synthesized primarily through mitochondrial oxidative phosphorylation (Berg et al., 2012). In humans, proteins and fats serve as principal sources of energy, especially under conditions consistent with a hypercarnivorous diet.

ATP Production Pathways and Energy Sources:

ATP production begins with the metabolism of dietary proteins and fats. Proteins provide amino acids, some of which are deaminated to enter the citric acid cycle, generating electron donors for the electron transport chain (ETC) in the mitochondria (Soeters et al., 2019). Meanwhile, fatty acids undergo beta-oxidation, generating acetyl-CoA molecules that also fuel the citric acid cycle (Berg et al., 2012). The electrons produced drive the ETC, creating a proton gradient that enables ATP synthesis.

A hypercarnivorous diet, high in animal proteins and fats, enhances ATP production via oxidative pathways rather than carbohydrate metabolism. This adaptation to animal-sourced nutrients allows efficient energy extraction and conserves ATP for essential functions such as active transport, muscle contraction, neurotransmission, and DNA repair (Lieberman, 2007). Essential nutrients like amino acids, fatty acids, vitamins, and minerals serve not just as fuel but as structural and regulatory molecules, ensuring optimal function across bodily systems (Voet et al., 2016).

B. Essential Amino Acids and Their Functions Across Physiological Systems:

The human body cannot synthesize the nine essential amino acids, which must be sourced from the diet. These amino acids are vital for supporting various biochemical processes across multiple physiological systems.

1. Histidine

- Endocrine: As a precursor to histamine, histidine plays a role in immune response and adrenal function (Berg et al., 2012).

- Nervous System: Histamine, derived from histidine, acts as a neurotransmitter, regulating sleep-wake cycles and cognitive alertness (Ross et al., 2014).

- Hematopoietic: Integral to hemoglobin structure, histidine is crucial for oxygen transport (Gropper et al., 2018).

2. Isoleucine

- Musculoskeletal: Supports muscle protein synthesis, repair, and energy production (Geissler and Powers, 2017).

- Endocrine: Regulates blood glucose levels by modulating insulin sensitivity (Soeters et al., 2019).

- Cardiovascular: Supports hemoglobin production, aiding in oxygen transport (Fairfield and Fletcher, 2002).

3. Leucine

- Musculoskeletal: Activates the mTOR pathway, promoting muscle protein synthesis and tissue repair (Cunningham, 2019).

- Endocrine: Modulates insulin and glucose homeostasis (Ross et al., 2014).

- Digestive: Aids in gut tissue repair and integrity (Geissler and Powers, 2017).

4. Lysine

- Integumentary: Crucial for collagen production, supporting skin, tendon, and cartilage health (Voet et al., 2016).

- Cardiovascular: Enhances calcium absorption, essential for vascular function (Cunningham, 2019).

- Immune: Plays a role in antibody production and immune response modulation (Ross et al., 2014).

5. Methionine

- Digestive: Supports detoxification in the liver as a methyl donor in reactions critical for cellular detoxification (Fairfield and Fletcher, 2002).

- Nervous: Aids in DNA methylation, influencing gene expression and neural health (Lichtenstein and Russell, 2005).

- Integumentary: Supports hair and nail health through sulfur-containing compounds (Berg et al., 2012).

6. Phenylalanine

- Nervous: Precursor to dopamine, epinephrine, and norepinephrine, impacting mood and mental focus (Gropper et al., 2018).

-Endocrine: Supports adrenal function by providing precursors to stress hormones (Geissler and Powers, 2017).

- Integumentary: Contributes to skin pigmentation through melanin synthesis (Ross et al., 2014).

7. Threonine

- Integumentary: Involved in collagen and elastin production, supporting skin and connective tissues (Bailey et al., 2015).

- Immune: Aids in antibody synthesis, enhancing immune defence (Lichtenstein and Russell, 2005).

- Nervous: Supports neurological balance through its role in glycine and serine production (Gropper et al., 2018).

8. Tryptophan

- Nervous: Precursor to serotonin and melatonin, regulating mood and sleep (Lieberman, 2007).

- Digestive: Aids in niacin production, which is necessary for digestive health (Ross et al., 2014).

- Reproductive: Influences reproductive health by regulating hormonal balance (Fairfield and Fletcher, 2002).

9. Valine

- Musculoskeletal: Aids in muscle tissue repair and regeneration (Geissler and Powers, 2017).

- Immune: Contributes to immune cell function and energy production under exertion (Semba, 2016).

- Endocrine: Assists in maintaining stable glucose levels (Soeters et al., 2019).

C. Essential Fatty Acids and Their Physiological Roles:

Essential fatty acids, primarily omega-3 and omega-6 fatty acids, cannot be synthesized by the body and play vital roles across physiological systems.

1. Alpha-Linolenic Acid (ALA)

- Cardiovascular: Reduces inflammation, supports vascular health, and improves elasticity (Zhao, 2015).

- Immune: Precursor to anti-inflammatory agents, modulating immune responses (Simopoulos, 2002).

- Integumentary: Maintains skin hydration and barrier function (Brisson et al., 2014).

2. Eicosapentaenoic Acid (EPA)

- Nervous: Supports cognitive function and reduces neuroinflammation (Erickson et al., 2015).

- Cardiovascular: Reduces blood clotting risk and inflammation in blood vessels (Brisson et al., 2014).

- Immune: Modulates immune response, reducing the likelihood of chronic inflammation (Cunningham, 2019).

3. Docosahexaenoic Acid (DHA)

- Nervous: Critical for brain and retinal structure, facilitating cognitive function and visual acuity (Holick, 2007).

- Reproductive: Supports foetal brain development during pregnancy (Semba, 2016).

- Musculoskeletal: Reduces joint inflammation, supporting joint health (Cunningham, 2019).

4. Linoleic Acid (LA)

- Integumentary: Essential for maintaining skin hydration and preventing dryness (Brisson et al., 2014).

- Reproductive*: Important in hormone synthesis and cell membrane function (Fairfield and Fletcher, 2002).

5. Arachidonic Acid (AA)

- Nervous: Involved in neural signalling and brain function (Zhao, 2015).

- Musculoskeletal: Supports muscle growth and repair by influencing inflammatory responses (Ross et al., 2014).

- Immune: Involved in immune cell function and inflammatory response (Simopoulos, 2002).

- Cardiovascular: Plays a role in vascular integrity and blood pressure regulation (Fairfield and Fletcher, 2002).

D. Essential Vitamins and Their Physiological Roles Across Systems:

Vitamins are organic compounds crucial for human health. Although they do not provide energy themselves, they facilitate countless biochemical reactions essential for metabolic health and overall physiological function.

1. Vitamin A (Retinol)

- Immune: Vital for maintaining the integrity of mucosal surfaces, enhancing immune defence (Semba, 2016).

- Integumentary: Supports skin health through collagen production and wound healing.

- Reproductive: Involved in foetal development and reproductive health by influencing cell differentiation (Geissler and Powers, 2017).

2. Vitamin C (Ascorbic Acid)

- Cardiovascular: Antioxidant that protects blood vessels from oxidative stress, reducing cardiovascular risk (Fairfield and Fletcher, 2002).

- Integumentary: Essential for collagen synthesis, maintaining skin elasticity and aiding wound repair (Ross et al., 2014).

- Immune: Enhances white blood cell function, increasing infection resistance (Lichtenstein and Russell, 2005).

3. Vitamin D

- Skeletal: Facilitates calcium absorption, crucial for bone density and structural integrity (Holick, 2007).

- Immune: Modulates immune function, reducing inflammation and supporting defense against pathogens (Bailey et al., 2015).

- Endocrine: Influences insulin secretion and pancreatic function, impacting glucose homeostasis (Geissler and Powers, 2017).

4. Vitamin E (Tocopherol)

- Integumentary: Protects skin cells from oxidative damage, aiding in skin repair (Fairfield and Fletcher, 2002).

- Immune: Enhances immune response by protecting immune cells from oxidative damage (Ross et al., 2014).

- Cardiovascular: Prevents lipid peroxidation, protecting heart and vascular health (Cunningham, 2019).

5. Vitamin K

- Hematopoietic: Essential for blood clotting by enabling synthesis of clotting factors (Gropper et al., 2018).

- Skeletal: Supports bone health by modifying bone proteins, which improves calcium binding (Ross et al., 2014).

- Cardiovascular: Reduces arterial calcification, promoting cardiovascular health (Lichtenstein and Russell, 2005).

6. B Vitamins (B1, B2, B3, B5, B6, B7, B9, B12)

- Nervous: Supports neurotransmitter synthesis and nerve function, crucial for cognitive health (Lieberman, 2007).

- Digestive: Facilitates energy extraction from macronutrients via coenzymatic actions in cellular respiration (Geissler and Powers, 2017).

- Cardiovascular: B12 and folate prevent homocysteine buildup, lowering cardiovascular risk (Fairfield and Fletcher, 2002).

E. Essential Minerals and Their Physiological Roles Across Systems:

Minerals are inorganic elements integral to structural and regulatory functions within the human body.

1. Calcium

- Skeletal: Primary component of bones and teeth, essential for structural integrity (Ross et al., 2014).

- Muscular: Enables muscle contraction by interacting with actin and myosin (Berg et al., 2012).

- Cardiovascular: Essential for vascular contraction and blood clotting (Holick, 2007).

2. Iron

- Hematopoietic: Central component of haemoglobin and myoglobin, critical for oxygen transport (Gropper et al., 2018).

- Immune: Supports lymphocyte and macrophage function, aiding immune defence (Fairfield and Fletcher, 2002).

- Nervous: Involved in dopamine synthesis, influencing cognition and mood (Bailey et al., 2015).

3. Magnesium

- Skeletal: Integral to bone structure and involved in calcium regulation (Lichtenstein and Russell, 2005).

- Nervous: Regulates neurotransmitter release, aiding in nervous system stability (Ross et al., 2014).

- Muscular: Assists muscle relaxation after contraction (Geissler and Powers, 2017).

4. Zinc

- Immune: Vital for immune cell function, supporting lymphocyte and antibody production (Semba, 2016).

- Integumentary: Supports skin health by aiding wound healing and preventing cellular damage (Fairfield and Fletcher, 2002).

- Reproductive: Critical for sperm production and hormonal balance (Gropper et al., 2018).

5. Potassium

- Cardiovascular: Regulates blood pressure by maintaining fluid and electrolyte balance (Cunningham, 2019).

- Nervous: Ensures proper nerve impulse transmission and muscle contraction (Voet et al., 2016).

- Muscular: Works with sodium to maintain cellular fluid balance, supporting muscle function (Bailey et al., 2015).

6. Selenium

- Endocrine: Integral to thyroid function, converting thyroid hormones to their active form (Geissler and Powers, 2017).

-*Immune: Protects cells from oxidative stress, aiding in immune response (Lichtenstein and Russell, 2005).

- Cardiovascular: Acts as an antioxidant, reducing risk of cellular damage in cardiovascular tissues (Brisson et al., 2014).

7. Iodine

- Endocrine: Essential for thyroid hormone synthesis, regulating metabolism and growth (Ross et al., 2014).

- Reproductive: Necessary for foetal brain development during pregnancy (Holick, 2007).

- Nervous: Supports cognitive function by regulating metabolic rate and neural development (Bailey et al., 2015).

Gluconeogenesis and the Non-Essentiality of Exogenous Carbohydrates

The existence of gluconeogenesis - the process by which the body produces glucose from non-carbohydrate precursors - accompanied by the fact that it runs continuously, provides compelling evidence that exogenous carbohydrates are not merely non-essential for human beings, but are not actually what our physiology is expecting to be used as our primary energy source.

That’s correct - the human body has the inherent ability to synthesize all necessary glucose internally from proteins and fats obtained via the diet. In fact, this process (gluconeogenesis) is so efficient and effective that humans maintain healthy blood glucose levels even in the complete absence of dietary carbohydrates.

1. Gluconeogenesis Runs Continuously:

- Gluconeogenesis operates continuously at a basal level, even during times when carbohydrates are readily available in the diet. The body synthesizes glucose primarily from amino acids (from protein) and glycerol (from fat), even in a well-fed state (Burgess et al., 2005). This continuous process demonstrates that humans do not depend on external carbohydrate sources to maintain glucose homeostasis.

- In fact, gluconeogenesis is the body's primary mechanism for maintaining glucose levels and this is true not only during periods when dietary carbohydrates are absent, such as during fasting or starvation (Cahill, 2006).

Hormonal Regulation of Gluconeogenesis

1. Endogenous Control:

- Hormones such as insulin, glucagon, epinephrine, and cortisol regulate gluconeogenesis based on the body’s glucose requirements. Insulin inhibits gluconeogenesis when glucose is abundant, while glucagon and other catabolic hormones increase gluconeogenesis when blood glucose levels drop, ensuring a stable supply of glucose even in the absence of dietary intake (Gerich, 1998; Klover et al., 2009).

- The regulation of gluconeogenesis by these hormones demonstrates that the body is fully capable of managing glucose production without external carbohydrates, adjusting the rate of gluconeogenesis according to metabolic demand.

Conclusion

Human physiology relies on nutrients beyond mere energy balance requirements to maintain optimal health. Our physiology evolved and adapted to extract and utilize essential amino acids, fatty acids, vitamins, and minerals to support specific biochemical and physiological processes across all bodily systems, ensuring cellular function, structural integrity, and metabolic balance.

Modern dietary patterns would suggest that carbohydrates are our primary energy source, but closer examination of our physiology sheds light on the fact that exogenous carbohydrates are utterly non-essential - suggesting that our health is perhaps better served by focusing our dietary choices on the foods which provide our essential nutrients in the most nutrient dense and bioavailable forms (i.e. animal-based foods).

This integrated perspective on nutrition highlights the importance of these nutrients in achieving health outcomes beyond ATP production, underscoring their role in maintaining the complex interplay of human physiology.

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