SEMINAR/LECTURE NOTE ON MY PRESENTATION.pptx

THIAMINE (VITAMIN B1), THE ULTIMATE GAME CHANGER IN HUMAN HEALTH AND CLINICAL PRACTICE; THE SERIOUSLY UNDERUTILIZED VITAMIN

1. THIAMINE (VITAMIN B1), THE ULTIMATE GAME CHANGER IN HUMAN HEALTH AND CLINICAL PRACTICE; THE SERIOUSLY UNDERUTILIZED VITAMIN BY DR. OLUWAYOMI PETER OLADELE (B.PHARM, PHARM D, MCPAN).

2. CONTENTS Introduction Why Thiamine Thiamine Deficiency Symptoms Prevalence of Thiamine Deficiency Thiamine Deficiency Diseases and Clinical Evidence of Thiamine Supplementation Benefits. Types of Thiamine Thiamine Supplementation Protocols Conclusion References

3. INTRODUCTION Thiamine ( Vitamine B1), is the first water soluble vitamin to be discovered. Discovered in 1897 by a Dutch physician , Eijkman, but isolated in 1934 by Jansen and Donath . Thiamine is on World Health Organization Essential Medicine List. It is present in many food products such as cereals, legumes, fruits, meat and poultry, vegetables and milk. It is easily destroyed by cooking and other food processing methods such as baking. These and other activities lead to deficiency of this important vitamin. Nutritional deficiency had been a major cause of many human diseases. Rather than looking for the cause , we specialize in treating the effects. "When diet is wrong, medicine is of no use, and when diet is correct, medicine is of no need." - Prof W.O Erhun . According to a 2020 article published in the BMJ, " one of every fine deaths across the globe is attributable to sub- optimal diets, more than any other risk factors .

4. WHY THIAMINE We discussed in our last lecture series that the health of the biomolecule in the cell, dictates the overall health of the cells, and subsequently the overall health of the body. If a biomolecule is rich in electron, it functions normally. If it is electron deficiency, it is diseased. It turns out that the overall health of the mitochondrial translate to the overall health of the body. Thiamine is a very vital factor for the biochemical functions of the mitochondrial

5. FUNCTIONS OF THIAMINE IN MITOCHONDRIAL Thiamine facilitate the conversion of pyruvate to acety 1-CoA in citric acid cycle heading to ATP production. In the nervous system, adequate Thiamine is critical for nerve cell metabolism and function as neurons rely heavily on glucose metabolism. Thiamine helps generate NADPH, essential for maintaining cellular resox state and redox balance.

6. THIAMINE DEFICIENCY SYMPTOMS We look from thiamine insufficiency to gross thiamine deficiency. Thiamine insufficiency symptoms includes -Loss of appetite - poor digestion - chronic constipation - loss of weight - mental depression - nerve exhaustion and insomnia - muscle weakness - leg cramp - slow heart beaf - defective gastric acid production - fatigue and loss of strength in the heart's auricle and subsequent development of cardiomegally and heart hypertrophy.

7. “GROSS THIAMINE DEFICIENCY INCLUDES” Beriberi, and Wernicke - Korsakoff Syndrome BERIBERI We have four types of beriberi Dry Beriberi This affects the nervous system with the following symptoms. -Peripheral neuropathy -Muscle weakness, leading to difficulty in walking and maintaining balance. - Loss of deep tendon reflexes - Wasting and progressive muscle atrophy.

8. WET BERIBERI This affects the cardiovascular system with more acute and severe symptoms. - Cardiomegally - Tachycardia - Congestive heart failure - Edema and -Shortness of breath If not promptly treated , wet beriberi can develop rapidly and often life threatening.

9. INFANTILE BERIBERI This affects infants typically between 2 to 6 months of age , who are breastfed by mother with thiamine deficiency. Symptoms includes: Cyanosis Persistence and severe vomiting Convulsions Cardiac symptoms Infantile beriberi is a medical emergency and immediate treatment with thiamine is crucial to prevent permanent damage or death.

10. GASTROINTESTINAL BERIBERI This type is less commonly discussed and has symptoms related to the digestive system. Common symptoms includes abdominal pain, nausea, vomiting and diarrhea. This symptoms will further impair thiamine abosorption , creating vicious cycle

11. CAUSES OF THIAMINE INSUFFICIENCY AND THIAMINE DEFICIENCY Poor nutritional intake Acute / chronic alcoholism Certain medical conditions such as chronic diarrhea , malabsorption syndrome, celiac disease, hyperthyroidism etc. Critically ill patients, patients with sepsis, trauma or burns . Prolong use of intravenous nutrition. Renal replacement therapy such as dialysis Diuretic use High carbohydrate intakes, especially refine carbohydrate. Certain foods containing thiaminase and anti- thiamine such as raw fish, coffee and tea. Pregnancy and breastfeeding

12. PREVALENCE OF THIAMINE DEFICIENCY Thiamine deficiency diseases or symptoms are frequently overlooked, misdiagnosed or under diagnosed. One study conducted post - northern analysis to investigate possible thiamine deficiency in 131 cases. The study found that 80% of cases were missed while the patients were alive. Only 16% of patients present with classical symptoms. Study shows that 15-29% of obsessed patients; 40-76% of Diabetes patients; up to 30% of psychiatry population; 20-50% of elderly and 10-30% of hospitalized patients are thiamine deficient.

13. THIAMINE DEFICIENCY DISEASES AND CLINICAL EVIDENCES OF THIAMINE SUPPLEMENTATION BENEFITS. CARDIOVASCULAR DISEASES The heart requires adequate thiamine level to maintain optimal function Wet Beriberi normally present with acute and severe cardiovascular symptoms. Clinical Evidence Clinical trials have demonstrated that thiamine Supplementation can improve left ventricular ejection fraction (LVEF) and all cardiac functions in heart failure patients. Thiamine Supplementation has shown favourable improvement in biomarkers related to heart diseases, such as B-type natriuretic peptide (BHP), which is elevated in hearth disease.

14. CLINICAL EVIDENCE Clinical trials have demonstrated that thiamine Supplementation can improve left ventricular ejection fraction (LVEF) and all cardiac functions in heart failure patients . Thiamine Supplementation has shown favourable improvement in biomarkers related to heart diseases, such as B-type natriuretic peptide (BNP), which is elevated in heart disease

15. DIABETES CLINICAL BENEFITS Thiamine has been shown to improve glucose metabolism, thereby reducing blood sugar levels and improving insulin sensitivity. By enhancing the function of transketolase , thiamine reduce the formation of advance glycation end product (AGEs) and reduce reactive oxygen species (ROS). Thiamine pyrophosphate (TPP) directly help reduce the formation of AGE. Thiamine role in nerve function helps in the management of diabetes neuropathy

16. CLINICAL EVIDENCE A clinical trial reported in diabetologia found that thiamine therapy reduces albuminuria , a marker of kidney damage in type -2 diabetes. Another studies published in the journal of Diabetes and it's complications stated that benfotiamine improve symptoms of diabetes neuropathy. Another study again published in Diabetic Care demonstrated that high dose Thiamine therapy significantly reduces blood glucose level in the type-2 diabetes

17. SEPSIS Sepsis is a life threatening condition characterized by a severe systemic inflammatory response to infection, leading to organ dysfunction and high mortality rate. Studies have found that 20-70% of septic patients are thiamine deficient. Sepsis often leads to cardiovascular dysfunction but thiamine improves myocardial function.

18. CLINICAL EVIDENCE Study in the journal of critical care reported that thiamine administration reduce the incidence of acute kidney injury (AKI) in septic patients. Another study published in the critical care medicine found that thiamine administration was associated with reduced mortality in septic patient with thiamine deficiency. Elevated lactate level are a marker of tissue hypoxia and poor prognosis in sepsis. Thiamine Supplementation has been shown to enhance lactate clearance, improve metabolic acidosis and patient outcome

19. THIAMINE USE IN CANCER THERAPY Cancer patients are at increase risk of thiamine deficiency due to several reasons including poor diet, increased metabolic demands and the effects of chemotherapy and radiation therapy. Thiamine helps cancer patients maintain their energy levels and improve overall quality of life, particularly during intensive treatment like chemotherapy. Thiamine has been prove to reduce the incidence of chemo-induced neuropathy. Cancer treatment often increase oxidative stress, contributing to cellular damage and side effects. Thiamine reduce oxidative stress and protect healthy cell during cancer treatment.

20. CLINICAL EVIDENCE A study in oncology reported that thiamine Supplementation reduce the incidence of neuropathy in patients receiving cisplastint based chemotherapy. A pilot study published in the of clinical oncology found that high dose Thiamine Supplementation significantly reduce fatigue in a subset of cancer patients.

21. THIAMINE AND NEURODEGENERATIVE DISEASES Neurodegenerative diseases, including Alzheimer's, parkinson's , and huntington's are characterized by progressive loss of Neuronal functions and structure, often lead to metabolic dysregulation and oxidative stress.

22. ALZHEIMER'S DISEASE ( AD) Thiamine deficiency had been linked to AD It may help improve cognitive function and slow disease progression

23. PARKINSON'S DISEASE (PD) Parkinson's involve degeneration of doperminergic neurones in the substantial nigra . Mitochondria function is a key feature in PD and thiamine role in maintaining mitochondrial function is particularly relevant.

24. WERNICKE KORSAKOFF SYNDROME (WKS) This condition involve severe thiamine deficiency, often due to chronic alcohol abuse. It presents with confusion, ataxia and memory loss. Thiamine is crucial for treating WKS.

25. CLINICAL EVIDENCE Alzheimer’s Disease. A study published in “Pharmacology Biochemistry and Behaviour ” found benfotiamin improve cognitive function and reduce oxidative stree markers in AD patients.

26. Parkinson’s Disease A case published in BMS case reports described PD pateints who experienced symptoms improvement with high dose thiamine supplementation.

27. WERNICKE – KORSAKOFF SYNDROME Thiamine supplementation is the primary treatment for WKS with high intravenous thiamine often uesd .

28. THIAMINE IN PREGNANCY AND BREASTFEEDING Pregnant women have greater need for the vitamin than other adults, especially during the third trimester. Pregnant women with hyperemesis gravidarum are at increase risk of thiamine deficiency due to losses through vomiting. In lactating women, thiamine is delivered in breast milk even if it results in deficiency in the mother. It has been suggested that thiamine deficiency hinders brain development in infant and may be a cause of sudden infant death syndrome (SIDs). SID is an unexplained death of a child less than one year of age . The diagnosis required that the death remained unexplained even after a thorough autopsy. SID usually occur during sleep typically between the hour of midnight and 9.00 am. SIDs remain the leading cause of infant mortality in western counties, constituting half of all post neonatal deaths.

29. TYPES OF THIAMINE Thiamine mono-nitrate This thiamine salt is cheap and widely available. It is commonly found in low quality supplement. It is used in food fortification

30. THIAMINE HYDROCHLORIDE This thiamine salt is also cheap to purchase and widely available. Broken down in the gut to free thiamine and absorbed ad dietary thiamine would. Generally, all thiamine salts exhibit: Poor intestinal absorption Estimated oral bioavailability is 3-8%, limited by saturable transporter. Require high doses (200-2000mg) to achieve clinical benefit.

31. BENFOTIAMINE The chemical name is s- benzoy thiamine -0-monophosphate It is synthesized in Japan to treat beriberi. It is synthesized to get a more bioavailable form of thiamine. It has improved absorption and hydrolyzed to thiamine in the liver . The free thiamine can the be transported to various body organs including the Brian. Bioavailability is 5-10 times the thiamine salts. Well studied in diabetic neuropathy and complications. Drawbacks It cannot enter cells without transporter. It requires breakdown in the gut, liver and RBC before use.

32. THIAMINE TETRAHYDROFURFURY DISULFIDE (TTFD) Disulfide derivative synthesized in Japan. It is soluble in water because of it chemical structure, yet freely passes through lipid membrane. It bypasses all known transport system. It has extremely high rate of absorption in the intestine and move freely into cells. Percentage bioavailability is unknown but old research showed bioequivalent to IV administration. Saturate multiple organs and can bypass blood brain barrier.

33. THIAMINE SUPPLEMENTATION PROTOCOLS Recommendations for thiamine Supplementation is as follow, though optimal dose and route of administration in critical cases are still under investigation. Thiamine Deficiency (Beriberi) Oral Administration Adults: 50-100mg daily Children:10-25mg daily Intravenous or Intramuscular Administration. Adult:50-100mg three times daily until symptoms resolve Children:10-25mg three times daily.

34. WERNICKE KORSAKOFF SYNDROME Intravenous administration Initial dose: 200mg -500mg three times daily for 3-5days. Maintenance dose: 250mg daily until clinical improvement. Oral follow up 100mg daily for extended period.

35. CRITICAL ILLNESS (SEPSIS,HEART FAILURE) Intravenous administration Sepsis: 200mg-500mg twice daily for several days. Heart Failure: 100-300mg daily for up to 7 days or more . Diabetes Neuropathy Oral Benfotiamine 300-600mh daily Alzheimer's Disease and Cognitive Decline. Benfotiamine : 300-600mg daily, often combine with other treatment.

36. NOTE! For some severe cases , you may not see good result until the IV dose reaches 1500-2000mg/day. High dose thiamine can deplete the body of potassium and magnesium causing hypokalemia and hypomagnesemia respectively . Therefore , regular checking of the mineral and Supplementation may be necessary.

37. CONCLUSION Knowledge of nutrition and nutritional deficiency is important in our daily practice and should therefore be taken seriously.

38. REFERENCES Thiamine as a metabolic resuscitator in septic shock: A meta - Analysis of Randomized controlled trials. Frontiers in Medicine 2023. Synthetic Thioester of Thiamine; promising tools for slowing progression of Neurodegenerative diseases: international Journal of Molecular sciences 2023. Thiamine in Critical Care; Clinical Implications for Septic Shock. Society of Critical Care Medicine 2023.