Essential Water-Soluble Vitamins

General Properties of Water-Soluble Vitamins

1. General Properties of Water-Soluble Vitamins

2. Recommended Daily Allowance (RDA)

✔ Solubility in Water – Easily dissolves in water-based fluids (blood, intracellular compartments).
✔ Limited Storage – Excess amounts are excreted in urine, thereby reducing the risk of toxicity.
✔ Frequent Dietary Need – Must be consumed regularly to prevent deficiency.
✔ Coenzyme Function – Many B vitamins act as enzyme cofactors in metabolism.
✔ Sensitive to Heat & Light – Can degrade during cooking or food processing.

✅Higher needs during pregnancy/lactation for fetal development and maternal health.
✅ Deficiency risk increases with poor diet, malabsorption conditions, and aging.

Vitamin C is a powerful antioxidant essential for collagen synthesis, immune function, and iron absorption.

Since humans cannot synthesize it, daily intake from fruits and vegetables is crucial to maintain optimal plasma levels and prevent deficiencies.

• Adults (Male/Female) ==== 90 mg / 75 mg

• Pregnant Women ==== 85 mg

• Lactating Women ==== 120 mg

  ✔ Higher intake needed in smokers and stressed individuals.
  ✔ Prolonged deficiency leads to scurvy (poor wound healing, bleeding gums).

1. Chemistry of Vitamin C

• Molecular Formula: C₆H₈O₆

• Structure: Contains a lactone ring with hydroxyl groups, allowing electron donation (antioxidant activity).

• pH Sensitivity: Easily oxidized, sensitive to heat and light degradation.

✔ Acts as a reducing agent, neutralizing reactive oxygen species.
✔ Essential for enzymatic reactions in hydroxylation and collagen formation.

2. Biosynthesis of Vitamin C (Not in Humans)

✔ Synthesized in most animals and plants via the gulonolactone oxidase pathway.
✔ Humans lack gulonolactone oxidase, preventing endogenous synthesis.
✔ Dietary intake is required to maintain plasma levels.

3. Plasma Levels and Metabolism

✔ Normal Plasma Range: 0.4 – 1.7 mg/dL.
✔ Stored in leukocytes, adrenal glands, and brain tissue for functional use.
✔ Excess is excreted via urine, reducing toxicity risk.

Vitamin C (ascorbic acid) is a water-soluble antioxidant essential for collagen synthesis, immune support, and iron absorption. Humans cannot synthesize vitamin C, making dietary intake crucial.

3. Vitamin C: Chemistry, Biosynthesis, Plasma Levels

4. Recommended Daily Allowance (RDA)

5. Dietary Sources

✔ Raw fruits & vegetables provide maximum vitamin C.
✔ Cooking reduces content, so minimal heat exposure is recommended.

Vitamin C plays a critical role in health by boosting immunity, reducing inflammation, protecting cells from oxidative damage, and supporting collagen formation. Let's explore how it interacts with diseases and nutrients.

6. Vitamin C in Disease Prevention & Nutrient Interactions

Role of Vitamin C in Disease Prevention

Vitamin C’s Interactions with Other Nutrients

A. Immune Support & Infection Defense

✔ Enhances white blood cell function to fight infections.
✔ Reduces the severity and duration of colds and respiratory infections.
✔ Supports wound healing by increasing collagen synthesis.

B. Cardiovascular Health

✔ Protects against oxidative stress that contributes to heart disease.
✔ Improves blood vessel function by promoting nitric oxide production.
✔ Reduces LDL oxidation, lowering atherosclerosis risk.

C. Cancer Prevention

✔ Neutralizes free radicals, reducing DNA damage.
✔ Enhances iron absorption, supporting healthy cell function.
✔ Shows potential in high-dose intravenous therapy for cancer treatment (under research).

D. Neuroprotection & Cognitive Function

✔ Protects neurons from oxidative damage, reducing Alzheimer's disease risk.
✔ Improves neurotransmitter synthesis, supporting mood and mental health.

Vitamin C plays a critical role in health by boosting immunity, reducing inflammation, protecting cells from oxidative damage, and supporting collagen formation. Let's explore how it interacts with diseases and nutrients.

Vitamin C (ascorbic acid) plays critical roles in collagen synthesis, bile acid formation, antioxidant defense, immune function, and neurotransmitter production.

1. Role in Collagen Formation

✔ Essential for the hydroxylation of proline & lysine, stabilizing collagen structure

✔ Supports skin, cartilage, tendons, and blood vessels, ensuring tissue strength.

✔ Deficiency leads to scurvy, causing bleeding gums, fragile skin, and poor wound healing.

2. Role in Bile Acid Formation

✔ Vitamin C is required for cholesterol metabolism, leading to bile acid production.
✔ Helps convert cholesterol into bile acids, supporting fat digestion.
✔ Deficiency impairs bile synthesis, increasing cholesterol levels and gallstone risk.

7. Functions of Vitamin C

3. Other Important Roles

1. Iron Metabolism

✔ Enhances non-heme iron absorption in the intestine, preventing anemia.
✔ Reduces ferric (Fe³⁺) to ferrous (Fe²⁺) form, making it bioavailable for hemoglobin synthesis.

2. Role in the Adrenal Gland

✔ Concentrated in the adrenal cortex, supporting cortisol and stress hormone synthesis.
✔ Prevents oxidative damage, stabilizing adrenal function.

3. Folate Metabolism

✔ Protects folate from oxidative breakdown, maintaining its bioavailability.
✔ Supports DNA synthesis and methylation pathways, crucial for cell division.

4. Tyrosine Metabolism

✔ Required for hydroxylation of tyrosine, aiding in protein synthesis.
✔ Involved in melanin formation, supporting skin pigmentation and UV protection.

5. Synthesis of Catecholamines

✔ Essential for dopamine, norepinephrine, and epinephrine synthesis, influencing mood and stress response.
✔ Hydroxylates dopamine to norepinephrine, regulating neurotransmission.

8. Vitamin C: Roles in Various Biological Processes

6. Tryptophan Metabolism

✔ Supports serotonin biosynthesis, improving mental well-being and sleep cycles.
✔ Reduces kynurenine accumulation, protecting against neuroinflammation.

7. Formation of Osteocalcin

✔ Activates osteocalcin, ensuring calcium binding for bone mineralization.
✔ Deficiency weakens bone integrity, increasing fracture risk.

8. Antioxidant Function

✔ Neutralizes free radicals, preventing oxidative damage.
✔ Regenerates vitamin E, ensuring continuous cellular protection.

9. Immunoglobulin Formation & Phagocytic Function

✔ Boosts B-cell immunity, supporting antibody production.
✔ Enhances neutrophil activity, improving pathogen clearance.

10. Carnitine Biosynthesis

✔ Required for hydroxylation reactions in carnitine formation, aiding fatty acid metabolism.
✔ Enhances mitochondrial energy production, reducing fatigue.

11. Conversion of Methemoglobin to Hemoglobin

✔ Reduces methemoglobin (Fe³⁺) back to hemoglobin (Fe²⁺), preventing hypoxia.
✔ Vital for oxygen transport and red blood cell function.

👉Final Take

Vitamin C is a powerful cofactor in metabolic pathways, essential for iron absorption, adrenal function, neurotransmitter synthesis, antioxidant defense, immune regulation, and oxygen transport. Its deficiency can lead to severe systemic dysfunctions, emphasizing its necessity for health.

9. Vitamin C Deficiency: Detailed Manifestations

1. Early Signs of Vitamin C Deficiency

✔ Fatigue & Weakness – Due to impaired mitochondrial energy production.
✔ Poor Wound Healing – Reduced collagen synthesis weakens tissue repair.
✔ Easy Bruising – Capillary fragility increases bleeding risk.
✔ Dry Skin & Hair Loss – Collagen breakdown affects dermal health.

Vitamin C (ascorbic acid) is essential for antioxidant protection, immune function, collagen synthesis, and iron absorption. Its deficiency leads to serious systemic dysfunctions, the most severe form being scurvy.

2. Severe Deficiency: Scurvy

Scurvy occurs after prolonged deficiency (weeks to months). It leads to:

A. Skin & Mucosal Symptoms

✔ Petechiae & Purpura – Small red spots caused by ruptured capillaries.
✔ Gingival Swelling & Bleeding – Inflamed gums, potential tooth loss.
✔ Hyperkeratosis – Rough skin texture, follicular plugging.

B. Connective Tissue & Joint Manifestations

✔ Joint Pain & Swelling – Weak connective tissue causes arthritis-like pain.
✔ Muscle Degeneration – Loss of collagen weakens muscle integrity.
✔ Bone Fragility – Reduced osteoblast activity increases fracture risk.

C. Cardiovascular & Hematologic Effects

✔ Capillary Fragility – Leads to easy bleeding and internal hemorrhages.
✔ Anemia – Reduced iron absorption contributes to fatigue and pallor.
✔ Hypotension – Weak vascular integrity affects blood pressure regulation.

D. Neurological Symptoms

✔ Depression & Irritability – Affects neurotransmitter synthesis (dopamine, serotonin).
✔ Cognitive Decline – Memory impairment due to oxidative stress.

4. Prevention & Management

3. Risk Factors for Vitamin C Deficiency

✔ Malnutrition & Poor Diet – Low fruit and vegetable intake.
✔ Smoking & Alcoholism – Increased oxidative stress raises vitamin C demands.
✔ Gastrointestinal Disorders (IBD, Celiac Disease) – Impairs absorption.
✔ High Stress & Chronic Illness – Raises vitamin C requirements.

✔ Consume vitamin C-rich foods – Citrus fruits, berries, peppers, leafy greens.
✔ Supplementation for at-risk individuals – Helps prevent scurvy and oxidative damage.
✔ Address underlying conditions – Improve absorption and reduce oxidative burden.

👉Final Take

Vitamin C deficiency manifests as fatigue, poor wound healing, gum disease, joint pain, anemia, and neurological dysfunction. Maintaining adequate intake through diet or supplementation prevents severe complications, e.g., scurvy.

10. Hypervitaminosis C (Vitamin C Toxicity)

1. Causes of Hypervitaminosis C

✔ Excessive Supplementation – High-dose vitamin C intake beyond recommended limits.
✔ Renal Dysfunction – Impaired kidney function leading to accumulation.
✔ Prolonged High Intake – Chronic excessive consumption over time.

Vitamin C is water-soluble, meaning excess amounts are generally excreted in urine. However, high-dose supplementation (>2,000 mg/day) can lead to adverse effects.

2. Symptoms and Health Risks

3. Risk Factors

✔ Kidney Disease – Increased risk of oxalate stone formation.
✔ Genetic Disorders (G6PD Deficiency) – High-dose vitamin C may trigger hemolysis.
✔ Iron Storage Disorders (Hemochromatosis) – Excess vitamin C enhances iron absorption, increasing toxicity risk.

4. Management & Prevention

✔ Maintain recommended intake (75–90 mg/day for adults).
✔ Avoid excessive supplementation beyond 2,000 mg/day.
✔ Increase hydration to reduce kidney stone risk.

👉Final Take

While vitamin C is beneficial in moderate amounts, excessive intake can lead to gastrointestinal distress, kidney stone formation, and metabolic imbalances. Proper regulation of vitamin C intake ensures optimal health without toxicity risks.

11. Vitamin C: Interactions with Medications and Nutrient Absorption

Vitamin C plays a major role in nutrient metabolism, but it can also interact with medications, affecting their efficacy and side effects. Let’s explore its influence on drug interactions and nutrient absorption.

1. Interactions with Medications

2. Impact on Nutrient Absorption

✔ Boosts iron and folate bioavailability, but excessive amounts may disrupt calcium levels.

✔ Works with vitamin E to enhance antioxidant defense.

✔ Patients on blood thinners should moderate vitamin C intake to avoid clotting issues.
✔ Cancer patients should consult doctors before taking high-dose vitamin C.

👉Final Take

Vitamin C interacts with anticoagulants, chemotherapy drugs, and lipid regulators, which may impact treatment outcomes. It enhances iron and folate absorption but may alter calcium balance if overconsumed. Understanding these interactions ensures optimal health without adverse effects.

B-Complex group

a. Energy-releasing B vitamins

These act as coenzymes in carbohydrate, fat, and protein metabolism.

• Vitamin B1 (Thiamine) – coenzyme as Thiamine pyrophosphate

• Vitamin B2 (Riboflavin) – coenzyme as FMN and FAD

• Vitamin B3 (Niacin / Nicotinic acid / Nicotinamide) – coenzyme as NAD⁺ and NADP⁺

• Vitamin B5 (Pantothenic acid) – part of Coenzyme A

• Vitamin B7 (Biotin) – a coenzyme in carboxylation reactions

2. B-Complex Vitamins as Coenzymes

c. Other B vitamins (related to metabolism and growth)

• Vitamin B6 (Pyridoxine, Pyridoxal, Pyridoxamine) – coenzyme as PLP (pyridoxal phosphate)

5. Causes of Water-Soluble Vitamin Deficiency

B-complex vitamins play critical roles in enzyme function, acting as coenzymes to support metabolic pathways, energy production, and biochemical reactions. Below is a summary of their coenzyme forms and functions:

1. Classification:

The B-complex vitamins are broadly classified into two functional groups & rest come under the third group:

a. Energy-releasing B vitamins

b. Hematopoietic (blood-forming) B vitamins

c. Other B vitamins (related to metabolism and growth)

b. Hematopoietic (blood-forming) B vitamins

These are essential for the synthesis and maturation of blood cells.

• Vitamin B9 (Folic acid) – coenzyme as tetrahydrofolate

• Vitamin B12 (Cobalamin) – coenzyme forms: Methyl cobalamin, deoxyadenosylcobalamin

The B-complex vitamins are a group of water-soluble vitamins that function mainly as coenzymes in various metabolic reactions, especially those involving the metabolism of carbohydrates, proteins, and fats.
They are essential micronutrients, not synthesized in adequate amounts in the human body, and therefore must be obtained from the diet.

✔ These coenzyme forms activate metabolic enzymes, ensuring proper biochemical function.
✔ They support ATP production, nervous system health, and cell division.

👉B-complex vitamins serve as essential coenzymes, driving metabolic reactions, energy synthesis, and cellular processes. Their deficiency leads to serious dysfunctions affecting metabolism, neurological health, and red blood cell formation.

✔ A balanced diet ensures sufficient intake and prevents deficiencies.
✔ Fortified foods help maintain optimal levels, especially for vegans and vegetarians.

4. Deficiency Symptoms of B-Complex Vitamins

3. Dietary Sources of B-Complex Vitamins

Adequate intake of B-complex vitamins is essential for metabolism, nervous system function, and red blood cell production. Deficiency leads to various health issues, affecting multiple body systems. B-complex vitamins are critical for cellular metabolism, neurological health, and red blood cell formation. Deficiency leads to serious health issues, emphasizing the need for a nutrient-rich diet and supplementation if necessary.

Water-soluble vitamin deficiencies occur due to insufficient intake, impaired absorption, increased demand, or excessive loss. Below are the key causes for deficiencies in B-complex vitamins

1. Dietary Deficiency (Inadequate Intake)

✔ Malnutrition – Poor dietary habits or restricted food consumption.
✔ Low Intake of Fresh Fruits & Vegetables – Leads to vitamin C deficiency.
✔ Vegan/Vegetarian Diets Without Fortification – Risk of B12 deficiency, as it is found primarily in animal products.

2. Malabsorption Disorders

✔ Gastrointestinal Diseases – Conditions like Crohn’s disease, celiac disease, and irritable bowel syndrome (IBS) reduce nutrient absorption.
✔ Pancreatic Disorders – Affect B-vitamin metabolism and digestion.
✔ Post-Surgical Changes (Gastric Bypass) – Reduced ability to absorb B12 and other vitamins from food.

3. Increased Vitamin Demand

✔ Pregnancy & Lactation – Higher need for folate, B12, and vitamin C.
✔ Illness & Infections – Increase vitamin C consumption for immune function.
✔ High Physical Activity – Demands more B-complex vitamins for energy metabolism.

4. Excessive Loss of Vitamins

✔ Chronic Diarrhea or Vomiting – Leads to depletion of B-complex and vitamin C.
✔ Alcoholism – Impairs thiamine, folate, and B6 metabolism, leading to severe neurological complications.
✔ Diuretics & Medications – Cause excessive loss of water-soluble vitamins through urine.

👉Water-soluble vitamin deficiency arises from poor diet, malabsorption, increased physiological demand, and excessive loss. Maintaining balanced nutrition and addressing underlying health issues prevents deficiencies and supports overall well-being.

B-Complex group

1. Thiamine (Vitamin B1):

Thiamine (Vitamin B1) is an essential water-soluble vitamin required for energy metabolism, nerve function, and carbohydrate processing.

1. Chemistry of Thiamine

✔ Molecular Formula: C₁₂H₁₇N₄OS
✔ Structure: Contains a thiazole ring and pyrimidine moiety, forming the active coenzyme Thiamine Pyrophosphate (TPP).
✔ Water-Soluble & Heat-Sensitive: Can degrade with excessive cooking or processing.

2. Biosynthesis of Thiamine

✔ Synthesized by bacteria, fungi, and plants—humans must obtain it through diet.
✔ Gut microbiota may contribute small amounts, but not enough to meet daily needs.
✔ Requires phosphorylation to form active TPP, essential for enzyme function.

3. Functions of Thiamine

✔ Vital for ATP production, making it critical for metabolism and nerve health.

4. Plasma Levels of Thiamine

✔ Normal Range: 70–180 nmol/L
✔ Stored in the liver, skeletal muscle, and nervous system in small amounts.
✔ Excess is excreted via urine, reducing toxicity risk.

5. Recommended Daily Allowance (RDA)

✔ Higher needs during pregnancy, stress, and increased metabolic activity.

7. Deficiency Manifestations

✔ Common in alcoholics, malnourished individuals, and those with malabsorption disorders.

6. Dietary Sources of Thiamine

✔ Whole grains and lean meats are excellent sources of thiamine.
✔ Refined foods lose thiamine during processing, increasing deficiency risks.

👉Thiamine is crucial for carbohydrate metabolism, nerve function, and ATP production. Deficiency leads to serious neurological and cardiovascular disorders, making adequate intake essential for overall health.

B-Complex group

2. Riboflavin (Vitamin B2):

Riboflavin (Vitamin B2) is a water-soluble vitamin essential for energy metabolism, cellular respiration, and antioxidant defense.

5. Recommended Daily Allowance (RDA)

✔ Increased demand during growth, pregnancy, and high metabolic activity.

1. Chemistry of Riboflavin

✔ Molecular Formula: C₁₇H₂₀N₄O₆
✔ Structure: Composed of a ribitol sugar linked to a flavin ring.
✔ Light-Sensitive: Easily degraded by UV exposure, making storage conditions critical.

2. Biosynthesis of Riboflavin

✔ Synthesized in bacteria, fungi, and plants, but not in humans.
✔ Humans must obtain it from dietary sources, making regular intake necessary.
✔ Converted into its active coenzyme forms:

• Flavin Mononucleotide (FMN)

• Flavin Adenine Dinucleotide (FAD)

3. Functions of Riboflavin

4. Plasma Levels of Riboflavin

✔ Normal Range: 5–25 nmol/L
✔ Stored in the liver, heart, and kidneys but quickly depleted without intake.
✔ Excess is excreted through urine, which is indicated by bright yellow coloration.

6. Dietary Sources of Riboflavin

✔ Dairy products and organ meats are excellent sources.

7. Deficiency Manifestations (Ariboflavinosis)

✔ Common in malnourished individuals, alcoholics, and those with absorption disorders.

👉Riboflavin is essential for energy metabolism, enzyme activation, and antioxidant defense.

Deficiency leads to skin disorders, neurological dysfunction, and oral health issues. Regular dietary intake is crucial for maintaining optimal health.

B-Complex group

3. Niacin (Vitamin B3):

Niacin (Vitamin B3) plays a key role in energy metabolism, DNA repair, and cellular health. It exists in two forms: nicotinic acid and nicotinamide, both of which are precursors to the coenzymes NAD and NADP.

1. Chemistry of Niacin

✔ Molecular Formula: C₆H₅NO₂
✔ Structure: Pyridine ring with a carboxyl group (Nicotinic acid) or an amide group (Nicotinamide).
✔ Water-Soluble & Heat-Stable: Resistant to cooking losses.

✔ Active form: Converts to NAD (Nicotinamide Adenine Dinucleotide) & NADP (Phosphate form) for metabolic reactions.

2. Biosynthesis of Niacin

✔ Endogenous Synthesis from Tryptophan – 60 mg of tryptophan produces 1 mg of niacin.
✔ Requires Vitamin B6, Riboflavin, and Iron as cofactors in synthesis.
✔ Liver is the primary site for niacin conversion from tryptophan.

✔ Dietary intake is still necessary, as synthesis is limited.

3. Functions of Niacin

✔ Vital for cellular metabolism, neurological health, and cardiovascular stability.

4. Plasma Levels of Niacin

✔ Normal Range: 0.5–8 µg/mL
✔ Stored in small amounts, primarily in the liver.
✔ Excess is converted into metabolic intermediates or excreted via urine.

6. Dietary Sources of Niacin

✔ Animal-based foods contain preformed niacin; plant-based foods contribute via tryptophan conversion.

5. Recommended Daily Allowance (RDA)

✔ Higher requirements during pregnancy, metabolic stress, and high-energy expenditure.

7. Deficiency Manifestations (Pellagra)

✔ Pellagra is common in malnutrition and impaired niacin metabolism.

👉Niacin is essential for cellular metabolism, neurological function, and antioxidant defense.

Deficiency leads to pellagra, manifesting as dermatitis, diarrhea, and cognitive decline. Adequate intake through diet and supplementation prevents deficiency complications.

Biosynthesis of Niacin

Niacin (Vitamin B3) is essential for cellular metabolism, DNA repair, and neurological function. It can be obtained through diet or synthesized endogenously from tryptophan.

1. Biosynthesis of Niacin from Tryptophan

✔ Precursor: Tryptophan (an essential amino acid)
✔ Conversion Efficiency: 60 mg of tryptophan produces 1 mg of niacin
✔ Key Enzymes Involved:

• Tryptophan 2,3-Dioxygenase (TDO) – Initiates conversion in the liver.

• Kynurenine Pathway – Intermediate stage producing quinolinic acid

• Quinolinic Acid Phosphoribosyl Transferase (QPRT) – Converts quinolinic acid into niacin

✔ Requires Vitamin B6, Riboflavin, and Iron as cofactors.
✔ Impaired biosynthesis occurs in liver disease or B6 deficiency.

2. Biomedical Significance of Niacin

✔ Critical for metabolic stability, cardiovascular health, and cognitive function.
✔ Used in therapeutic interventions for dyslipidemia and neurological disorders.

👉Niacin is biosynthesized from tryptophan via the kynurenine pathway, requiring cofactor vitamins (B6, riboflavin) for optimal efficiency. Biomedical significance encompasses metabolic energy production, cardiovascular health, and neuroprotection, making it a vital nutrient.

Hypervitaminosis of Niacin (Vitamin B3 Toxicity)

1. Causes of Niacin Toxicity

✔ High-Dose Supplementation – Doses exceeding 500–2,000 mg/day.
✔ Extended-Release Niacin – Higher risk of liver toxicity compared to immediate-release forms.
✔ Medical Use for Cholesterol Management – Prescription-strength niacin may cause side effects.

Niacin toxicity occurs when excessive doses of niacin are consumed, typically from high-dose supplements rather than food sources. While niacin is water-soluble, excessive intake can lead to adverse effects.

2. Symptoms of Niacin Toxicity

3. Risk Factors for Niacin Toxicity

✔ Individuals taking high-dose niacin for cholesterol management.
✔ People with pre-existing liver disease or diabetes.
✔ Long-term use of extended-release niacin formulations.

✔ Monitoring liver function is essential for those on high-dose niacin therapy.

B-Complex group

4. Pantothenic Acid (Vitamin B5):

B-Complex group

5. Pyridoxine (Vitamin B6):

B-Complex group

6. Biotin (Vitamin B7):

B-Complex group

7. Folic Acid (Vitamin B9):

B-Complex group

8. Cobalamin (Vitamin B12):

B-Complex group

9. Inositol, Choline, & PABA: