TOPIC 3A MOLECULAR BASIS OF MICRONUTRIENTS AND PHYTOCHEMICALS IN HEALTH.pptx

Nutraceuticals

1. MOLECULAR BASIS OF MICRONUTRIENTS AND PHYTOCHEMICALS IN PREVENTION & TREATMENT OF CHRONIC DISEASES ( CARDIOVASCULAR & CANCER). BY: ABDUL AZIZ KARIM 1

2. OUTLINE Chronic diseases Cardiovascular diseases Cancer History of nutrition Micronutrients and phytochemicals Deficiency and toxicity of micronutrients and phytochemicals Molecular mechanisms of micronutrients in the prevention & treatmentof CVD and cancer Molecular mechanisms of phytochemicals in the prevention & treatment of CVD and cancer 2

3. Chronic diseases Chronic diseases are long term health conditions that often progress slowly and require ongoing management . They are a leading cause of mortality and morbidity worldwide, significantly impacting healthcare systems and economics. 3

4. COMON TYPES OF CHRONIC DIESEASES 4

5. Epidemiology of chronic diseases Chronic diseases account for  74% of all deaths globally  and 37% of deaths in Africa  (WHO, 2023) Cardiovascular diseases  are the leading cause, responsible for approximately  17.9 million deaths annually worldwide and 1.1 million deaths annually  in Africa, many under age 60 (WHO Africa, 2023) Cancer  causes nearly  10 million deaths annually worldwide and r esponsible for  12% of deaths  annually in Ghana, with breast, cervical, and prostate cancers most common. 5

6. Epidemiology of chronic diseases Obesity  has tripled since 1975, with over  650 million adults  classified as obese. Diabetes  affects over  537 million adults  worldwide, with numbers rising due to obesity and sedentary lifestyles. Chronic diseases consume  30-40% of Ghana’s health budget , straining a system already battling infectious diseases. 6

7. Risk factors of chronic diseases Modifiable Risk Factors Unhealthy diets (high in salt, sugar, and fat). Physical inactivity. Tobacco use and excessive alcohol consumption. Air pollution and environmental factors. Non-Modifiable Risk Factors Age (risk increases with aging). Genetics and family history. 7

8. Cardiovascular diseases Cardiovascular disease (CVD) refers to a group of disorders affecting the heart and blood vessels. These conditions are primarily driven by atherosclerosis (plaque buildup in arteries) and hemodynamic dysfunction, which disrupt blood flow and oxygen delivery to vital organs. 8

9. Cardiovascular diseases Link to Risk Factors: Modifiable Risks : Unhealthy diets (high salt/sugar/fat) → endothelial dysfunction, dyslipidemia, and hypertension. Physical inactivity → obesity, insulin resistance, and poor circulation. Tobacco/alcohol → oxidative stress, vasoconstriction, and arrhythmias. Air pollution → systemic inflammation and oxidative damage. Non-Modifiable Risks : Aging → arterial stiffening and reduced regenerative capacity. Genetics → inherited lipid disorders or hypertension susceptibility. 9

10. Pathophysiology of cardiovascular diseases 10

11. Cancer and its Pathophysiology Cancer is a group of diseases characterized by uncontrolled cell proliferation and the ability to invade or metastasize to distant tissues. Its pathophysiology involves genetic mutations & altered cellular signal Genetic and Molecular Basis Oncogene Activation : Mutations in proto-oncogenes (e.g.,  RAS ,  MYC ) lead to hyperactivation of growth signals, driving uncontrolled cell division  Tumor Suppressor Gene Inactivation : Loss-of-function mutations in genes like  TP53  or  RB1  disable critical checkpoints for cell cycle regulation and apoptosis, allowing damaged cells to proliferate  DNA Repair Defects : Impaired DNA repair mechanisms (e.g., BRCA1/2 mutations) increase genomic instability, accelerating mutation accumulation  11

12. Pathophysiology of cancer 12

13. History of nutrition Humans have evolved from a preagricultural, hunter gatherer society to a commercial agricul t ure with highly processed, refrigerated and fast foods that have imposed an unnatural and unhealthy nutrition The human genetic makeup is 99.9% that of our Paleolithic ancestors, yet our nutritional, vitamin and mineral intakes are vastly different [Eaton et al. 2017]. 13 https://www.shutterstock.com/image-vector/infographic-development-human-nutrition-through-history-1975728527

14. History of nutrition M icronutrient variations contribute to the higher incidence of Chronic diseases including cancer and Cardiovascular diseases through a complex nutrient gene interaction. Identifying the risk factors that can be modified, and treatments remains to be a main concern for cancer & CVD prevention 14

15. Nutrient-gene interaction and health outcomes. 15

16. Micronutrients & phytochemeicals 16

17. Micronutreints &Phytochemicals Micronutrients and phytochemicals play a crucial role in maintaining health and preventing diseases. While micronutrients are essential vitamins and minerals required in small amounts for physiological functions, phytochemicals are Non-nutritive plant-derived compounds (e.g., polyphenols, carotenoids, glucosinolates) with bioactive properties. Synergistically, micronutrients and phytochemicals work to modulate cellular processes, reduce oxidative stress, improve immune function, and prevent chronic diseases such as cancer, cardiovascular diseases, diabetes, and neurodegenerative disorders. 17

18. Categories of micronutrients: Vitamins They are Organic compounds containing carbon, produced by living organisms (plants, animals) and are known as coenzymes to support enzymes in metabolic processes (e.g., Vitamin K for blood clotting). Water-soluble : B-complex vitamins  (e.g., B1, B6, B12, folate): Support energy metabolism, DNA synthesis, and red blood cell formation. Vitamin C : Antioxidant, collagen synthesis, and immune function. Fat-soluble : Vitamin A : Vision, immune function, and skin health. Vitamin D : Calcium absorption, bone health, and immune modulation. Vitamin E : Antioxidant protection of cell membranes. Vitamin K : Blood clotting and bone metabolism. 18

19. Categories of micronutrients: Minerals Inorganic elements derived from soil, water, and rocks and are known to serve structural (e.g., calcium in bones) and functional roles (e.g., iron in hemoglobin, sodium in nerve transmission Trace minerals  (needed in smaller amounts): Iron : Oxygen transport (hemoglobin), energy production. Zinc : Immune function, wound healing, DNA synthesis. Selenium : Antioxidant (glutathione peroxidase), thyroid function. Iodine : Thyroid hormone synthesis. 19

20. Deficiency and Toxicity of micronutrients and phytochemicals Micronutrient deficiencies are widespread and linked to chronic diseases including cancer and cardiovascular diseases (CVD).  In a study conducted by the hypertension Institute in Nashville, USA , found that correcting intracellular micronutrient deficiencies normalized blood pressure in  62% of hypertensive patients within 6 months, enabling discontinuation of antihypertensive drugs.   20

21. Deficiency and Toxicity of micronutrients and phytochemicals This integrative approach improves vascular health, reduces cardiovascular events (e.g., heart attacks, strokes), and lowers healthcare expenditures by addressing root causes (nutrient-gene interactions, oxidative stress) rather than just symptoms. Epidemiological studies suggest that high plasma levels of Selenium, carotenoids (phytochemicals) and ascorbic acid are protective against cancer. 21

22. Deficiency and Toxicity of Vitamins Micronutrient Deficiency Symptoms Toxicity Symptoms Vitamin A Night blindness, dry skin, immune dysfunction Hypervitaminosis A: Liver damage, bone pain, teratogenicity (birth defects) Vitamin D Rickets (children), osteomalacia (adults), weakened immunity Hypercalcemia: Kidney stones, calcification of soft tissues Vitamin E Neuromuscular dysfunction, hemolytic anemia Bleeding risk (anticoagulant effect) Vitamin K Impaired blood clotting, bleeding disorders Rare; may interfere with anticoagulant drugs Vitamin C Scurvy: Fatigue, gum disease, poor wound healing Diarrhea, kidney stones (high doses) B Vitamins Fatigue, anemia, neurological issues (e.g., B12 deficiency causes neuropathy) Rare; excess B6 can cause nerve damage Vitamins 22

23. Deficiency and Toxicity of minerals Micronutrient Deficiency Symptoms Toxicity Symptoms Iron Anemia, fatigue, weakened immunity Hemochromatosis: Liver damage, diabetes, heart issues Zinc Impaired immunity, hair loss, delayed wound healing Nausea, vomiting, immune suppression Magnesium Muscle cramps, arrhythmias, hypertension Diarrhea, cardiac arrest (very high doses) Calcium Osteoporosis, muscle cramps, tetany Hypercalcemia: Kidney stones, vascular calcification Selenium Cardiomyopathy ( Keshan disease), weakened immunity Selenosis: Hair loss, nail brittleness, neurological issues Iodine Goiter, hypothyroidism, developmental delays Hyperthyroidism, thyroiditis 23

24. Deficiency and Toxicity of common phytochemicals Phytochemical Deficiency Symptoms Toxicity Symptoms Curcumin Increased inflammation, oxidative stress Gastrointestinal issues, liver toxicity (high doses) Resveratrol Reduced antioxidant protection Limited toxicity; potential hormone disruption Quercetin Weakened antioxidant defense Headache, kidney damage (high doses) Catechins Reduced cardiovascular protection Liver toxicity (e.g., from excessive green tea extract) Lycopene Increased oxidative stress Rare; may cause gastrointestinal discomfort Sulforaphane Reduced detoxification capacity Thyroid dysfunction (excessive cruciferous intake) 24

25. Molecular mechanisms of micronutrients in the prevention & treatmentof CVD and cancer 25

26. Vitamins A Vitamins A (Retinoids & Carotenoids) Sources: Carrots, sweet potatoes, liver, spinach, dairy, tomatoes, gauva ., watermelon Function: Essential for vision, immune function, and epithelial integrity Deficiency: Night blindness, weakened immunity, increased infection risk 26

27. Vitamin A Mechanism of Action in Disease Prevention CVD prevention and management: Carotenoids (e.g., beta-carotene, lycopene) neutralize free radicals, reducing oxidative stress linked to atherosclerosis and endothelial dysfunction. Lycopene, a potent antioxidant, improve endothelial health by enhancing nitric oxide bioavailability leading to significant reduction in BP Cancer Prevention & treatment: Beta-carotene (a carotenoid) acts as an antioxidant, neutralizing free radicals that cause DNA damage. Retinoids inhibit tumor cell proliferation by regulating cell cycle arrest and apoptosis (programmed cell death). 27

28. Vitamin D (Cholecalciferol D2,Animal, Ergocalciferol D3 plant) Function: Regulates calcium homeostasis, supports immune function Deficiency: Rickets (children), osteomalacia (adults), weakened immunity 28

29. Vitamin D Mechanism of Action in Disease treatment & Prevention CVD management and prevention Vitamin D suppresses renin production, potentially lowering blood pressure by reducing angiotensin II (a vasoconstrictor). It inhibits pro-inflammatory cytokines (e.g., TNF-α, IL-6) linked to atherosclerosis. Cancer Treatment & Prevention: Inhibits proliferation of cancer cells by activating VDR, which regulates apoptosis and suppresses tumor growth. Reduces the risk of breast, colon, and prostate cancers. 29

30. Vitamin E (Tocopherols & Tocotrienols) Function: Antioxidant, protects lipid membranes from oxidative stress Deficiency: Nerve damage, muscle weakness, hemolysis 30

31. Vitamin E Mechanism of Action in Disease Prevention Antioxidant Function: Vitamin E donates an electron to neutralize free radicals, preventing lipid peroxidation in cell membranes. This protects against atherosclerosis and neurodegenerative diseases. Cardiovascular Protection: Prevents oxidation of low-density lipoprotein (LDL) cholesterol, reducing plaque formation in arteries. Lowers risk of coronary heart disease and stroke. Cancer Prevention: Tocotrienols inhibit angiogenesis (new blood vessel formation in tumors ). Suppresses oncogenic pathways like NF- κB (Nuclear factor kappa B), reducing cancer cell proliferation. 31

32. Vitamin K (Phylloquinone, Menaquinone) Function: Essential for blood clotting, bone mineralization Deficiency: Increased bleeding, osteoporosis 32

33. Vitamin K Mechanism of Action in Disease Prevention Cardiovascular Disease: Inhibits arterial calcification by regulating matrix Gla protein (MGP), mitigation of arterial stiffness, elastic properties of the carotid artery, and progression of arteriosclerosis. Blood Clotting (Coagulation Pathway): Vitamin K acts as a cofactor for the enzyme γ-glutamyl carboxylase, which activates clotting factors II, VII, IX, and X. Prevents hemorrhagic disorders. Bone Health: Activates osteocalcin, which binds calcium to bones, preventing osteoporosis. Reduces fracture risk in postmenopausal women. 33

34. Water-Soluble Vitamins (B-complex, C) Vitamin C (Ascorbic Acid) Function: Collagen synthesis, antioxidant, immune support Deficiency: Scurvy (bleeding gums, poor wound healing) 34

35. Vitamin C (Ascorbic Acid) Mechanism of Action in Disease Prevention & treatment (CVD& cancer) Duffy et al. (1999) Observed reduced BP in individuals with higher dietary vitamin C intake, particularly in hypertensive populations. Vitamin C scavenges free radicals, reducing oxidative stress and improving endothelial function. Promotes vasodilation, lowering peripheral vascular resistance. Lowers the risk of chronic diseases like cardiovascular disease and cancer. Vitamin C enhances TET enzyme activity, restoring normal DNA methylation patterns and suppressing tumor growth 35

36. Vitamin C (Ascorbic Acid)  High-dose (100g IV  ) generates hydrogen peroxide, selectively targeting cancer cells with metabolic vulnerabilities (Monti et al , 2012) A phase 2 trial in  advanced pancreatic cancer  reported doubled median survival (16 vs. 8 months) when IV vitamin C was combined with chemotherapy ( Polireddy et al, 2017) 36

37. Water-Soluble Vitamins (B-complex, C) Vitamin B-complex Function: Neurotransmitter synthesis, DNA synthesis, RBC production Deficiency: fatigue, weakness, and neurological issues 37

38. B Vitamins Mechanism of Action in Disease Prevention & Management (CVD& cancer) Randomized controlled trials found that supplementation with folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) reduced homocysteine levels by 18% compared to placebo One human study by Aybak et al . [1995] proved that high-dose vitamin B6 (5 mg/kg/day) significantly lowered BP (systolic BP by 8.4%and diastolic by 9.3%). Sources: peanuts, soya beans , leafy green vegetables, liver, breakfast cereals, Meat, fish, milk, cheese, eggs 38

39. B Vitamins Mechanism of Action in Disease Prevention & Management (CVD& cancer) Folate (vitamin B9)  contributes to methyl group donation, essential for DNA methylation. This process can silence or activate genes, such as tumor suppressor genes or oncogenes. Deficiency leads to uracil misincorporation into DNA, increasing cancer risk. Vitamin B12 and B6  support folate metabolism, indirectly influencing methylation patterns. Vitamin B6: Vitamin B6 is a cofactor in homocysteine metabolism, helping convert homocysteine to cysteine via the transsulfuration pathway. Elevated homocysteine levels are linked to endothelial damage, oxidative stress, and atherosclerosis. Adequate B6 intake reduces hyperhomocysteinemia , lowering CVD risk 39

40. Molecular mechanisms of micronutrients MINERALS Magnesium affects vascular smooth muscle by competing with Na+ and acting as a calcium channel blocker, leading to vasodilation and reduction in blood pressure. Zinc  is a cofactor for DNA repair enzymes and transcription factors like NF- κ B. Deficiency can impair antioxidant defenses and increase oxidative stress. Selenium  integrates into selenoproteins (e.g., glutathione peroxidase), which regulate redox-sensitive transcription factors like Nuclear factor erythroid 2-related factor 2 (Nrf2) -   a transcription factor that regulates cellular antioxidant responses and detoxification 40

41. Molecular mechanisms of phytochemicals Gene Expression Epigenetic Regulation : Resveratrol  (grapes, berries) activates sirtuins (SIRT1), deacetylating histones to promote longevity-related gene expression. Sulforaphane  (broccoli) inhibits histone deacetylases (HDACs), enhancing acetylation and activation of tumor suppressor genes. Quercetin (Onions, Apples) : Blocks CYP450 enzymes involved in activating procarcinogens (e.g., polycyclic aromatic hydrocarbons). 41

42. Molecular mechanisms of phytochemicals in the prevention & treatmentof CVD and cancer 42

43. Molecular mechanisms of phytochemicals Gene expression Signaling Pathways : Curcumin  (turmeric) suppresses NF- κ B and MAPK pathways, downregulating genes involved in inflammation and proliferation. Isoflavones  (soy) bind estrogen receptors, modulating genes affecting hormone-responsive tissues. 43

44. Molecular mechanisms of phytochemicals Inflammation Pathway Inhibition : Curcumin  inhibits COX-2 and LOX enzymes, reducing prostaglandin and leukotriene production. Quercetin  (onions, apples) blocks mast cell histamine release and NF- κ B activation. 44

45. Molecular mechanisms of phytochemicals Antioxidant and Nrf2 Activation : Sulforaphane  activates Nrf2, upregulating antioxidant response elements (e.g., glutathione synthesis genes), which counteract oxidative stress and inflammation. Epigallocatechin-3-gallate (EGCG)  (green tea) scavenges radicals and suppresses TLR4/NF- κ B signaling. Lycopene (Tomatoes) : Scavenges singlet oxygen, protecting DNA from oxidative damage. Downregulates cyclin D1, arresting cell cycle in G1 phase. 45

46. Molecular mechanisms of phytochemicals Apoptosis and Anti-Proliferation Epigallocatechin-3-gallate (EGCG, Green Tea) : Inhibits VEGF and MMPs, suppressing angiogenesis and metastasis. Activates caspases (e.g., caspase-3) to induce apoptosis in cancer cells. Lycopene (Tomatoes) : Scavenges singlet oxygen, protecting DNA from oxidative damage. Downregulates cyclin D1, arresting cell cycle in G1 phase. 46

47. REFERNCES Monti DA, mitchell E, bazzan AJ, littman S, zabrecky G, yeo CJ, pillai MV, newberg AB, deshmukh S, levine M. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. Plos one. 2012;7(1):e29794. Doi: 10.1371/journal.Pone.0029794. Epub 2012 jan 17. Pmid : 22272248; pmcid : pmc3260161. Polireddy k, dong r, reed g, et al.: High dose parenteral ascorbate inhibited pancreatic cancer growth and metastasis: mechanisms and a phase I/ iia study. Sci rep 7 (1): 17188, 2017 Blanca alabadi , miguel civera , and alfonso j cruz-jentoft nutrition based support for osteoporosis in postmenopausal women: a review of recent evidence, 2023 John howlett functional foods from science to health and claim, 2008, ILSI europe conscince monograph series. 47

48. REFERENCES Rajput, R., Wairkar , S. and Gaud, R., 2018. Nutraceuticals for better management of osteoporosis: An overview.  Journal of functional foods ,  47 , pp.480-490. Fahey, J.W. and Talalay, P., 1999. Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxication enzymes.  Food and chemical toxicology ,  37 (9-10), pp.973-979. Teerapong Rattanatantikul,Mart Maiprasert,Pansak Sugkraroek , 2020, Efficacy and Safety of Nutraceutical on Menopausal Symptoms in Post-Menopausal Women Takuathung , M.N., Teekachunhatean , S., Chansakaow , S., Klinjan , P., Inpan , R., Kongta , N., Tipduangta , P., Tipduangta , P., Dukaew , N., Sakuludomkan , C. and Koonrungsesomboon , N., 2024. The effects of SOY extract nutraceuticals on postmenopausal women’s health: A randomized, double-blind, placebo-controlled trial. Journal of Functional Foods, 113, p.10605 Trimarco , V., Rozza , F., Izzo, R., De Leo, V., Cappelli, V., Riccardi, C. and Di Carlo, C., 2016. Effects of a new combination of nutraceuticals on postmenopausal symptoms and metabolic profile: a crossover, randomized, double-blind trial.  International Journal of Women's Health , pp.581-587. 48