Water Soluble vitamins-Part 2

0:04 [music] Welcome you all to the week seven on water soluble vitamins part two. So we discussed on the uh B1, B2 and B3. We're going to the next three uh vitamins which is B6 pyodoxin, B12, cyanocobalamin, folate which is a B9. We are going to understand the at the end of the session the student will be able to understand the definition, functions, mechanism, dietary requirements, RDA, bioavailability, toxicity, food sources and stability of all the three vitamins

0:50 and their critical role in amino acid metabolism, [snorts] neurotransmitter synthesis. And in B12 it is the DNA synthesis, myelin formation and meloic anemia prevention. In folate it is the vital role in one carbon metabolism, DNA synthesis and neural tube defect prevention. The common features include um all the three particular nutrients which vitamins which we are going to discuss are interdependent and they work together in one carbon metabolism and they regulate the homocyine. Deficiency of any one of these will impair the function of the others. B12 and folate deficiency both will cause megaloblastic anemia which is

1:36 clinically important distinction and they are critical during pregnancy uh because the deficiency causes neurot defects which is the NTD and fetal growth restriction. So we'll start with B6 which is the major watersoluble vitamin. They exist in three natural forms which is the pyodoxin, pyodoxel and podoxamin. All are converted to the active co-enzyme form called puridoxal phosphate which is a PLP which participates in over 100 enzyatic reactions primarily involving amino acid metabolism and neurotransmitter synthesis. So the chemical forms uh include pyodoxin which is the PN paradox which is PL and paridoxamin which is a PM all

2:22 are getting converted to active PLP which is a parodoxal phosphate. This is the active form and all the activation happens via pyodoxal kynise enzyme using ATP which is the adinine triphosphate. It's stored primarily in the muscle about 80 to 90%age is stored in the muscle uh which is bound to glycogen phosphor phosphorase and also in the liver and the brain. deficiency disease includes per peripheral neuropathy uh saboric dermatitis, glossitis, irritability, confusion and microcyic anemia. So that's the major thing that we should concentrate on B6. The functions of uh B6 puridoxin includes a wide variety of metabolisms

3:10 starting from amino acid metabolism. Uh PLP forms as a co-actor uh in the transamination deamination decarboxilation reactions essential for synthesis and catabolism of all the amino acids. Whereas in the hemoglobin synthesis PLP forms as a co-actor for ALA synthesis first that's the first and the rate limiting step in the hemoglobin synthesis in the glycogen metabolism PLP forms as a co-actor for glycogen phosphorase mobilizing glucose from glycogen stores in the muscle. It has a lot of functions. Uh again uh starting with neurotransmitter synthesis. It is very much essential for

3:55 the synthesis of serotonin from tryptophan, dopamine and GABA norepinephrine and histamine. Nioin synthesis is also very much uh involved here where the conversion of tryptophan to nasin involves PLP which is the podoxil phosphate. In the lipid metabolism, it is involved in the synthesis of sphingo lipids, essential components of neuronal myelin sheath. It forms a major source of immune function where it is essential for lymphocytes proliferation and antibbody production. Deficiency impairs the cell mediated immunity. uh it is also involved in the steroid hormone modulation where uh it modulates the action of steroid hormone receptors

4:40 uh as glucocorticoid, estrogen and androgen receptors. The mechanism of action includes dietary vitamin B6 is absorbed in the junum where you can see that uh it is uh involved as a perodoxal kynise and ATP conversion results in the active form of podoxal phosphate. [snorts] This spirit phosphate forms a shift base with amino group of substrate amino acid and thereby it is involved in trans amamination decarboxilation transulfuration reactions. Coming to the ICMR recommendations uh it starts from 0.1 for infants and goes

5:27 up to 1.7 and two for lactation and pregnant women and for adult man men and women it is 1.6 6 mg and 1.5 mg respectively. The bioavailability uh includes 70 to 75%age from mixer diet nearly 100%age from supplements and the site include the jaginal part where passive diffusion takes place. [gasps] The animal sources include are having an higher bioavailability especially podoxil and podoxamin forms readily absorbed. So there the drug interactions include iside which is the tuberculosis drug being given pensilamin oral contraceptives or antagonize the B6

6:12 and they increase the requirements. The plant sources have very low bioavailability and uh plants uh from the plants it's only 50 to 60%age is bioavailable. Enhancing factors of riboflavin includes the adequate protein intake whereas reducing factors include alcohol. Uh so alcohol mostly destroys the PLP which is the podoxal phosphate and it impairs the absorption. Prolonged cooking also reduces the um PLP and also food processing. Whereas in the storage uh the B binding process 80%age is stored in muscle bound to uh glycogen phosphorase which is released

6:59 during the muscle breakdown or fasting. The toxicity uh effects there is not much of a toxicity that is reported from B6 especially from the food there is no toxicity reported and it's completely safe. The upper limit includes 100 mg per day from the supplements. uh sensory neuropathy happens if it's a most serious toxic effects when the dosages are greater than 200 mg per day which causes the peripheral uh sensory neuropathy and the numbness tingling sensation and also difficulty in walking. Photosensitivity happens when the high doses causes skin sensitivity to sunlight. [snorts] Ataxia uh would lead to loss of coordination and balance

7:46 at very high doses. greater than 500 mg per day. Reversibility happens uh when the neurological symptoms happens on stopping the supplements but recovery may be very slow. Unlike most B vitamins, B6 has a very clear upper limit of 100 mg per day. Sensory neuropathy is well doumented risk of supplemental overdose. And the food sources include with regard to uh B6 are uh non-veg sources have the highest values with chicken liver, tuna and salmon which is cooked. When it comes to the plant sources, uh banana being the highest source. Next is the potatoes and the chickpeas and sunflower

8:33 seeds also have good amount of uh B6 with about 1.35 mg per 100 g. Whole wheat also has good amount and fortified cereals will also have good amount of B6. The stability includes uh the vitamin B6 is moderately stable to heat but highly sensitive to UV light and alkaline conditions. Significant losses occur during prolonged cooking and food processing. Milling and refining of cereals destroy about 70%age of B6 content. Whole grains are always preferred over refined grains. Freezing of vegetables causes significant B6 losses up to 40%age due to leeching during blanching. Fresh vegetables preferred cooking water retains

9:20 significant B6 discarding the cooking water waste. This important micronutrient causes the uh discard of cooking water. Incorporating that particular water into soups and gravies is always recommended. that is why you you retain the B6 u levels in the cooking process. So coming to B6 uh deficiency it would lead to uh a lot of complications that we discussed in the previous slides of ours. So if you see the deficiency includes same as B3 pelgra uh then you have various immune functions and all that.

10:07 So the toxicity is really really rare and that's the B6 end. So we are moving to B12 which is the cyanocobalamin or the cobbalamament which is a very important water soluble vitamin which has a unique cobalt containing chlorine ring structure and that forms the most chemically complex of all the vitamins. It is essential for DNA synthesis, [gasps] myelin sheath formation, red blood cell maturation and homoyine metabolism. Chemical nature include the cobalt containing corin ring with the vitamin containing a metal ion which is the largest and the most structurally complex vitamin. The active form include methile cobbalamin which is a cyto is in

10:52 the cytoplasm and aden adinosil cobbalamin which is present in the mitochondria. The unique absorption of this particular B12 requires intrinsic factor which is the IF which is a glyoprotein which is secreted by the gastric paratital cells for its absorption and terminal elium. Always intrinsic factor is needed for B12 absorption. Coming to the storage, uh the vitamin is largely stored in the body with about 2 to 5 mg stored in the liver and its storage can last for five 3 to 5 years. So that's how the vitamin B12 is getting stored. If there is a deficiency that has to occur, the person has to be on

11:37 B12 deficiency for a longer period of time, then only the deficiency can occur. So that leads to megaloplastic anemia which is a subacute combined degeneration of spinal cord peripheral neuropathy and pernicious anemia. This pernicious anemia is mostly because of the intrinsic factor deficiency. So the main functions of B12 includes DNA synthesis which is the methile cobbalamin regenerating process which forms the tetrahydroofolate which is active folate and it's essential for thyidin synthesis and uh that leads to DNA replication in all dividing cells. The myelin formation happens with the which is essential for the myelin

12:23 sheath. Adinosyl cobbalamin is essential for myelin basic protein synthesis. Thereby it helps in the maintaining the integrity of neuronal milin sheath. Homocyine metabolism where methile cobbalamine forms as a co-actor for methionine synthes converting the homocyine to methionine. This particular um B12 is very important in that particular step of conversion. If the B12 is not available in the body, homoyine gets accumulated in the body and that causes the cardiovascular risk. If the homoyine is getting converted to methionine when the B12 is available that would reduce the cardiovascular risk. Uh so when it comes to methionine

13:10 synthesis always it produces methionine and it forms a SAM which is a S arinosel methionine which is a universal methile donor for DNA metallization metallization and neurotransmitter synthesis and it's also involved in the ochain fatty acid metabolism where adnosel cobbalamin forms as a co-actor for methile melano coa mutase converting the methile melan coa and the saxinal coa A required in the crep cycle. This red blood cell maturation happens with B12 where it is required for normal nuclear division in developing RBCs. So when there is a deficiency this causes a large immature meal blast that is why red blood cell

13:57 maturation requires B12. When it comes to energy metabolism, the energy metabolism happens via saxinal COA entry into crep cycle contributing to ATP production. The neurological function uh happens with regard to the synthesis of neurotransmitter where there is a maintenance of cognitive function and it prevents dementia. So the mechanism of B12 involves a variety of action. Here uh dietary B12 forms and the salivory R protein will bind the B12 in the stomach. The pancreatic proteasis will release the B12 from the R protein. B12 thereby binds with intrinsic factors secreted by

14:42 the gastric parietital cells. B12 and if complex is absorbed at the terminal process via the cubulin receptor. Now the B12 is released and it enters to the blood and the tissues. Now this is going to have two reactions. One is in the cytoplasm and one is in the mitochondria. In the cytoplasm methile cobbalamin is synthesized where you can see that homocyine plus methile THF with regard to the methonine synthes forms methionine and THF which is the active folate is regenerated. This is called the folate trap and this gets released and DNA synthesis is restored which is the reaction one. In

15:28 the reaction two happening in the mitochondria this is the adnosel cobbalamin where methylmel coa is formed in as in the saxinal coa in the crep cycle. The deficiency of methyl methyl maloinoic acid accumulates the methylinoic acid and that leads to the milein damage thereby causes neurological symptoms. So there are two different reactions that takes place with regard to the B12 and for B12 we need an intrinsic factor and R protein which gets uh from the saliva and it gets bound to the B12 in the stomach thereby causing the absorption at the terminal ilium. ICMR recommendations include about 0.2

16:15 for infants and it goes on uh with elderly about 04 and for pregnancy and lactation it is 0.5 mgram per day. Coming to the bioavailability uh the rate of bioavailability is about 40 to 60%age at normal dietary intake and they decrease significantly with high doses. If the intrinsic factor is available, there is an absolute uh absorption that take play takes place in the terminal ilium and the gastric acid also plays a very important role in the absorption of B12 where it releases the proteinbound B12 from the food achloro hydria where the low stomach acid is there. You can find that it will absorb the uh impair

17:01 the absorption profoundly and the passive absorption happens with about 1 percentage being absorbed by passive diffusion without the intrinsic factor relevant only with very high supplement doses and the animal sources include high bioavailability which is the B12. So it's naturally available in the animal foods. In the plant sources the absorption is not much and if you see algae and spiralina contains inactive B12 analoges. The reducing factors would lead to pernicious anemia where there is no intrinsic factor production. Gasterectomy when the stomach is removed metformin usages proton pump inhibitors and cron's disease affecting the

17:47 terminal elium will all cause a reduction in the B12 absorption. toxicity include uh there is not much of a toxic effect when it comes to the B12. It is extremely safe and there is no upper limit established from the food. There is no toxicity reported. Whereas from the supplements again if the dosage is very much high above 1,000 mug per day it is ex uh excreted in the urine and high dose uh IV if it's given there is a rare allergic reaction which is reported with parental administration. [snorts] uh the metformin will always reduce the B12 absorption by 30%age and especially for diabetic subjects who are taking metformin there will be a reduced B12

18:33 absorption. Therefore the diabetic patients need monitoring when they are given metformin. The toxic effects is like uh B12 is one of the safest vitamin known and there are no adverse effects from any oral dose. The only concern is if you're having an inadequate intake especially when they are vegetarians there would be a B12 deficiency. Coming to the food sources uh the non-vegetarian sources are the major forms of uh B12 having uh beef liver is the highest which is 70.7 m with salmon and eggs coming to the next level. Shellfish has the highest and also milk paneer has a little bit compared to the

19:18 animal sources. So we do have sardines, curd, yogurt and fortified plant milk. The stability uh of B12 is good when it compares to the other vitamins. B12 is relatively stable to heat during normal cooking. Whereas pasteurization of milk causes only 10 to 20 10 to 20 percentage loss. Boiling meat retains the most of the B12. B12 is strongly destroyed by UV light. When the milk is exposed to sunlight, it loses the significant B12. When the package is opaque, it is very good for preserving the B12 in the diary products. Alkaline conditions like baking soda, alkaline cooking rapidly

20:04 destroy B12. Uh so acidic conditions are more favorable for stability. Long-term storage and food processing causes gradual B12 degradation. Uh whereas fresh animal products is they always preferred over heavily processed forms. So B for maximum B12 content. Next we move on to the folate which is the major uh vitamin again which is the B9. Folate is a water-soluble V vitamin existing naturally in foods as polylutamate forms and synthetically as folic acid monoglutamate in supplements and fortified uh foods. It functions as a co-enzyme in one carbon transfer reactions essential for DNA synthesis, cell division, amino acid metabolism and

20:51 neural tube development. So when we talk about the discovery it is isolated in 1941 from spinach by Mitchell and named from Latin folium meaning the leaf. The chemical forms include the natural food folate which is a poly glutamate. Folic acid synthetic forms include the from supplements and fortification. Five metal tetrahydrofluor folate is the active circulating form. The activation includes like this whereas folic acid gets from dihydropholate to tetrahydrofolate via dihydropholate reductase. That's an enzyme which requires B12 for regeneration. So all the three vitamins that we are concentrating now are

21:37 interrelated. So deficiency includes megaloplastic enema just like B12 and apart from that there there are neural tube defects like spinaobida and anan capali in newborns. The active form includes tetrahydopolate the biological active co-enzyme form. The storage includes 5 to 10 mg stored primarily in the liver and the body [snorts] stores last only up to 3 to 4 months only. The functions of the folate include the DNA synthesis which is the tetrahydroof folate carries one carbon units for the synthesis of purin adinine guanine and thamidin essential for DNA replication in all dividing cells. The cell division occurs with rapid dividing cells in the

22:23 bone marrow the gastrointestinal epithelium and the fetus. A most dependent deficiency causes megaloblastic changes. The neural tube development is very much critical in the first 28 days of pregnancy. If the folate is adequate during this particular time, it will prevent the neural tube defects especially the spina bifida and dan and kefali homoyine metabolism as discussed in B12. It is very important for uh methionine synthes synthesis where the five methile tetrahydropholate donates the methile group to B12 in the presence of methionine synthes will convert the homocyine to methionine

23:08 reducing this cardiovascular risk. So in this particular step we need the methile tetrahydropholate and also B12. [snorts] The amino acid metabolism tetrahydroofolate is essential for the intercon conversion of serereine to glycine histadin metabolism and also methionine synthesis. A methylation reactions via SAM which is the S adinosel methionine from methionine is resulting in DNA meta methylation and gene regulation also in the neurotransmitter synthesis. The red blood cell formation is required for normal nuclear maturation of RBC's. The deficiency causes large immature megaloblast. The cancer prevention also

23:56 is very important. Adequate folate maintains the DNA integrity and methylation patterns. The low folate is always linked with colorctyl cancer. Coming to the mechanism. So there is a lot of uh involvement with regard to the folate. The dietary folate as polyglutamate is converted to intestinal conjugates removing the glutamate chain. Here the monoglutamate is absorbed in the jigunum which would see to that dihydropholate reductase is the major uh step there. Folate gets converted to dihydropholate as tetrahydrofluorate. Also tetrahydro folate accepts one carbon unit from serene glycine

24:42 histadine and formate. This will carry in different forms in the different reactions. Therefore this one carbon folate forms and functions are in the different pathways given as thyidate synthes purin synthesis and all that. Coming to the ICMR recommendation, uh the infants 0 to 6 months it is 25 mgram with regard to the dietary folate intake and it increases as they grow. Uh for adult men it is 200 m and for adult women it is 200 mg. For pregnancy it is 500 mg. For lactation it is 300 mg. For elderly it is 200 m. dietary folate per

25:29 day. So talking about the bioavailability, the food folate is 50% bioavailable. When it comes to polyglutamate forms, this forms must be hydrayed by intestinal conjugates before absorption. Folic acids in the form of synthetic is 85% bioavailable with food. Excuse me. Nearly 100%age is available on the empty stomach. this significantly uh more bioavailable than the food folate. The site of folate absorption is proximal junum uh which is the active transport mechanism and the B12 deficiency uh is required to regenerate the tetrahydroof folate from

26:17 five methyl tetrahydroofolate to B12 deficiency causes functional folate deficiency that's nothing but the folate trap [snorts] the enhancing factors include the gastric acid adequacy vitamin C and adequate B12 are all the enhancing factors for folate. The reducing factors include alcoholism where the alcohol might be the major cause of reduction of the absorption increasing the urinary excretion and blocks the folate metabolism. Cooking losses up to 50 to 70%age are lost during prolonged cooking and they are mostly heat liable of all the uh B vitamins. Coming to the toxicity uh there are not much of toxicity that is observed with

27:04 regard to uh folate uh completely safe with regard to the uh food sources. Upper limit include thousand muggram per day from synthetic folic acid and B12 deficiency will be masked if it's a major concern uh when the high folic acid is corrects the megaloplastic enemy of B12 deficiency without correcting the neurological damage [snorts] which could be irreversible nerve damage may progress the undetected. When it comes to zinc absorption, very high dos dosages of folate may impair the zinc absorption. If there is a high dosage of uh folate, this may reduce the seizure uh risk. With regard to epileptic patients on anticonvolesence

27:51 uh regarding the cancer risk, excessive folic acid supplementation may promote growth of pre-existing cancer cells particularly colorctyl cancer. This particular concept still remains controversial but there are evidences to say that excess folic acid can be a risk for uh this particular aspect. Food sources include chicken liver which is the highest beef liver uh spinach, black eyed peas, lentils, chickpeas and all that. And these are the major uh vegetable sources like chickpeas, aspberers, avocado, orange and fortified cereals. The stability of folate includes uh the most li heat liable of all the vitamins

28:38 up to 50 to 70%age is destroyed by prolonged boiling and cooking. Whereas steaming and microwave cooking are strongly preferred to preserve the folate content. It is highly sensitive to UV light and oxygen and it stored vegetables in uh cool dark and airtight conditions and leafy greens will lose the significant folate within three 2 to 3 days of room temperature storage. Alkaline cooking conditions uh rapidly destroy the folate. So avoid adding baking soda when cooking uh green vegetables. Acidic conditions, add lemon juice uh will help the preservation of folate. Synthetic folic acid in supplements and fortified foods is far more stable than natural food folate.

29:24 This is why fortification programs use folic acid rather than natural folate. So thereby I would like to conclude for these three nutrients are B6 which is paradoxin is moderately sensitive to heat which is lost during processing and the deficiency would lead to dermatitis, anemia and neurological symptoms. B12 cobbalamin is very much sensitive to heat and they are absent in plant foods. The deficiency leads to megaloplastic anemia and their irreversible uh nerve damage can occur. When it comes to folate B9 is easily destroyed by heat and leeching in water. The deficiency would lead to megaloblastic anemia and neural tube defects. Consuming all these

30:11 nutrients at right proportions can help you to uh avoid the deficiency and have a healthy uh living. Thank you. Uh happy learning.