1. Vitamins Organic compounds with no caloric value
Needed in very small doses for normal function, growth, and maintenance of the body
Body cannot make enough to maintain health
Absence from the diet creates deficiency symptoms that are corrected when vitamin is added
Amounts to prevent deficiencies are small
Humans need one ounce (28 grams) of vitamins for every 150 pounds (70 kg) of food consumed
Plants synthesize all they need
Animals (including humans) vary in which ones they can produce
For example, humans and guinea pigs do not make vit. C

2. Factors affecting vitamin content
Ripeness
Riper fruits & vegetables have more vitamins
Storage time
Vitamins degrade with longer storage, especially C, folate, & thiamin
Excessive cooking
Especially in water
Cooking heat can destroy some vitamins, especially prolonged cooking & reheating
Heat (in storage)
Enzymes degrade vitamins faster under warm conditions
Exposure to air
Oxidation occurs,especially when vegetables have been peeled
Alkalinity
destroys vitamin D, thiamin, and other vitamins

3. How to preserve vitamins in food
Keep fruits & vegetables cool till eaten
Refrigerate fruits & vegetables except bananas,onions, potatoes, & tomatoes in moisture-proof,airtight containers or in vegetables drawer
Trim & cut only enough to remove inedible parts
Steam, stir-fry, or microwave veges
Minimize cooking time
Don’t add fats to veges during cooking
Do not add baking soda to enhance green color
Store canned goods in cool, dry place
Store frozen foods at 0 degrees F or colder for 12 months maximum
Keep milk away from light to preserve riboflavin

4. Two categories of vitamins
Fat-soluble
Vitamins A,D, E, and K
Water-soluble
The B vitamins (thiamin, riboflavin, niacin, pantothenic acid, biotin, B6, folate, and B12)
Choline is related but not classified as a vitamin
Vitamin C

5. Fat-soluble vitamins are absorbed and stored with fat
Fat must be present for absorption
If fat absorption efficient, 40-90% get absorbed
They are taken up into micelles
They leave micelles and enter SI epithelial cells
There they reform triglycerides & get packaged in golgi
They travel in blood as part of chylomicrons
They are stored mostly in liver and fatty tissues
Mineral oil not absorbed; carries fat soluble vitamins to feces

6. Fat-soluble vitamins: Pre-formed Vitamin A
In a group called retinoids, with three active forms:
Retinol (alcohol form)
Retinal (aldehyde form, for vision)
Retinoic acid (organic acid form, regulates genes)
These three are only found in animal tissues and foods
Abundant in eggs, fish & fish oil, butter & other milk products, & animal livers
When stored or made into a supplement, it is in retinyl form:
Retinyl palmitate, retinyl acetate
90% of storage is in the liver
10% of it is in fat tissue, kidneys, and lungs

7. Vitamin A from plant carotenoids
Beta-carotene can be converted to vitamin A
One beta-carotene can be metabolized to form 2 molecules of retinal
This is not efficient, nor is beta-carotene absorption
Some people have genes that decrease their ability to do this
Other carotenoids are important in human health but don’t form vitamin A
These include lycopene, zeaxanthan, and lutein
Carotenoids are found in orange & yellow fruits & vegetables and leafy greens

8. Functions of vitamin A Maintains health of epithelial cells
(lining of lungs, intestine, stomach, vagina, urinary tract, eyes, skin)
Retinoic acid is also required for maturation of epithelial cells
Needed for maintaining mucus-forming cells
Keeps excess keratin from forming
It boosts tissue growth & repair
Helps maintain immunity

9. Vitamin A functions to maintain vision
Light enters through cornea and lens
Then it hits the retina
Light reacts with rhodopsin, a vit. A-containing compound in rod cells of retina
Rhodopsin is “bleached” by removing retinal
This stimulates impulse to brain
A new vit. A molecule then combines with opsin to replenish rhodopsin

10. Vitamin A deficiency Early symptoms Reduced vision Bitot’s spots
burning, itching, and inflammation of eyelids
Reduced vision
Especially at night or dim light
Nyctalopia
Bitot’s spots
White, foamy patches on white of eye
Build-up of cellular debris
Xerophthalmia
From prolonged, severe deficiency
Cornea gets dry, hazy, pigmented, wrinkled
Can get ulcerations
Tear glands dry up & eye no longer glistens
Eyelid is inflamed

11. Vitamin A deficiency, continued…
Dry and rough skin
Itchy, scaly; skin thickens
Especially on palms and soles, elbows
Also backs of arms and elsewhere

12. Vitamin A deficiency, continued…
Increased susceptibility to bacterial infections
Especially UTIs and respiratory tract
Epithelial cells in these areas dry out and makes them susceptible
Digestive juice secretion may also be restricted
This increases risk of intestinal infections & diarrhea
Problems inside mouth
Impaired healing
Increased risk of candidiasis
Dry mouth and increased risk of cavities
Decreased taste sensitivity
Did you know: There are three SNPS with genes coding for proteins involved in intestinal uptake, transport, and metabolism of carotenoids (SR-B1, CD36, and BCO1). Mutations in these are suspected to alter expression and/or activity of these proteins and in turn, carotenoid status & vit A deficiency.

13. Stunted growth from vitamin A deficiency
Functions in differentiation and maturation of cells during early fetal development
Needed for bone remodeling and growth
Binds to DNA receptors to increase synthesis of certain proteins
Deficiency can halt childhood development
Most often seen in undeveloped nations from poor nutrition
Stunted growth from vitamin A deficiency

14. Best to get Vitamin A from foods, not supplements
Diet high in Beta-carotene is associated with lower risk of skin, lung, bladder, breast, and oral cancers
Likely due to antioxidant activity
However, an important study showed that beta-carotene supplement use in 29,000 male smokers increased the number of lung cancer cases compared to control group
28% higher risk of lung cancer and a 17% higher risk of deaths from all causes
Supplement was higher than physiological dose

15. Too much vitamin A (pre-formed)
Can cause changes to vision, bone pain, liver damage and increased pressure on the brain
Chronic toxicity if >25,00 IU ingested for more than 6 years or >100,000 IU for more than 6 months
Early sign is dry lips
Dry, itchy, scaly skin with peeling palms & soles
Hair loss, follicular hyperkeratosis, and hyperpigmentation of face & neck
A single dose over 300,000 IU can cause acute toxicity
Dry scaly skin with large areas of desquamation and fissuring of lips and angles of the mouth
Infants: nausea & vomiting, drowsiness or irritability and increased intracranial pressure
Adults: drowsiness, irritability, headache, vomiting

16. Too much vitamin A in pregnancy
Linked to birth defects and poor pregnancy outcomes
Dangerous in early pregnancy because it binds to DNA and influences development
Can cause malformations and miscarriage
Pregnant women should limit vit. A supplements to 100% of RDA
Also avoid too much liver or fish oil

17. Too much Beta-carotene: Carotenosis or Carotenoderma
From excessive intake
Or deficiency of conversion enzyme
Skin turns yellow-orange
Especially palms & soles
It fades after intake is decreased
Mucous membranes are not affected
Not toxic
Absorption decreases as oral intake increases & conversion is slow
May be mistaken for jaundice
But whites of eyes do not turn yellow

18. Fat-soluble: Vitamin D (Calciferol or Calcitriol)
Steroid with hormone-like functions
Sources:
Made in skin (from cholesterol) on exposure to sun
Found in some foods
Animal foods have cholecalciferol (D3)
Many foods also fortified with this form
Some supplements have ergocalciferol (D2) from irradiating ergosterols from plants
But D3 is better at raising blood levels of vit D
D2 & D3 are not active until altered by liver & kidney
Active form is 1,25 dihydroxycholecalciferol (calcitriol)

19. Food sources of cholecalciferol
Fatty fish, like tuna, mackerel, and salmon; also fish oils
Wild-caught salmon is highest, with IU of vitamin D per 3.5 ounce serving
Farmed salmon has IU
Tuna has 300 IU per 6 ounces
Egg yolks (41 IU per yolk)
Beef liver (12 – 30 IU per 3.5 ounces)
Butter has some
Must eat too much fat to get enough
Foods fortified with vitamin D, like some dairy products, orange juice, soy milk, and cereals.
RDA is 600 IU (=15 mcg)/day

20. Manufacture & activation of vitamin D
From sunlight:
Vit D precursor (7- dehydrocholesterol) made when light hits cholesterol in skin
It’s changed to cholecalciferol and then 25-hydroxyvitamin D3 in liver
That is changed to 1,25- dihydroxyvitamin D3 (calcitriol, the active hormone form) in the kidney
From food:
Vitamin D2 and D3 from foods are sent to the liver and then kidney for activation
Vitamins: Vitamin D
Manufacture & activation of vitamin D

21. Getting enough vitamin D may be tricky
Need to spend 10 minutes in sun each day
This provides % of needs
Problem for those who work indoors or have high skin cancer risk
But without sun, body relies on foods
It is not in too many foods
If you live north of 42 degrees latitude, the sun’s rays have to pass through too much atmosphere in winter
Adequate vit. D not made
Must plan diet carefully to get enough
Otherwise, supplements are needed
Getting enough vitamin D may be tricky

22. Over-use of sunscreen has made us vitamin D deficient
9% to 40% of Americans—depending on age, ethnicity, and locale—are deficient in vitamin D
Some experts recommend exposing face & arms to sun for 5-10 min 2-3x/wk before applying sunscreen
A darker person needs more
Less time if sun intense
Solar D is a new Australian sunscreen that allows a percentage of UVB rays to penetrate

23. Calcitriol increases blood serum calcium levels:
Functions of vitamin D Vitamin D (the active calcitriol form) regulates blood calcium
Calcitriol increases blood serum calcium levels:
It increases Ca & P absorption
It increases reabsorption of Ca by kidney tubules
It may increase blood Ca by drawing from bone
Calcitriol works with parathyroid hormone (PTH) in those jobs
Parathyroid gland secretes PTH when calcium levels are low
This increases Ca absorption
PTH also stimulates the production of more calcitriol
In kidney, PTH promotes excretion of inorganic phosphate
When serum phosphate levels decrease, hydroxyapatite (Ca5(PO4)3OH—the main form of calcium in bone) dissolves out of the bone and increases serum calcium
Calcitonin, another hormone, increases bone Ca

24. Vitamin D binds to many types of cells in the body
Functions of vitamin D Vitamin D also regulates gene expression and cell growth
Vitamin D binds to many types of cells in the body
Brain & nervous system, immune system, parathyroid gland, pancreas, skin, muscles, reproductive organs, and more
These cells have VDR, vitamin D receptors
The receptor/vit D complex acts as a transcription factor
It migrates to the cell’s nucleus, binds to DNA, and alters gene expression
Affects risk of cancer (skin, colon, prostate, breast)
Affects risk of CVD, diabetes, hypertension
Did you know: Many people have mutations in VDR genes, which limits their ability to absorb and use itamin D

25. Functions of vitamin D Vitamin D is crucial in activating immune response
Immune cells called T-cells cannot react to a pathogen without vitamin D:
Phospholipase C is part of nearly all signal tranduction pathways in cells
When a T-cell needs to activate and proliferate, more PLC is needed
The T cell production of PLC is dependent on vitamin D and upregulation of VDR (vitamin D receptor)
Vit D plus VDR go into the nucleus and turn on gene for PLC
PLC is made, so signals can be sent in cell and T-cell can be activated

26. Functions of vitamin D Vitamin D plays a role in heart health
VDRs are found in cells throughout the cardiovascular system
A variety of experimental studies show that vit.D + VDR helps control cardiac hypertrophy and fibrosis, regulates blood pressure, and suppresses the development of atherosclerosis

27. Deficiency of vitamin D
When vit. D level is low, only 10-15% of calcium is absorbed
vs % when D level is normal
Not enough Ca to maintain bones
When this happens in infancy or early childhood, rickets develops
Bowed legs, thick wrists & ankles, spine curvatures, pigeon chest, skull and pelvic malformations
Not just in less developed countries
9% of US kids D-deficient in 2009

28. Bone problems from vitamin D deficiency
Greatest risk of D deficiency in:
Older adults (>60)
Especially if on meds that interfere with vit. D absorption
Those living in northern latitudes
Those who are rarely outside or who wear too much sunscreen
Osteomalacia
Bones are soft from D deficiency
They are porous, weak & breakable
Most common in those with kidney, stomach, gall bladder, cirrhosis, or intestinal disease
Osteopenia & Osteoporosis
Bones lose density with aging
Vit. D, calcium, magnesium, boron, vit. K2, & other nutrients important in prevention
Bone problems from vitamin D deficiency

29. Too much vitamin D Upper limit (UL) is 4000 IU/day (100 mcg)
This is based on risk of calcium overabsorption
Can cause bone loss by interfering with vitamin K2 activity
Calcium can deposit in kidneys and other organs
Can cause metabolic disturbances and cell death
Toxicity symptoms:
Weakness, loss of appetite, diarrhea, vomiting, mental confusion, decreased urine output, excessive thirst
Can cause calcium levels in blood to increase above the normal range (10 mg/dl)
Can contribute to kidney stones
Soft tissues can calcify, including lungs, heart, vessels
With sun, you can never get a toxic dose of D
If sun exposure increases, D production decreases

30. Fat-soluble: Vitamin E
Found in fat tissues and cell membranes
Includes four tocopherols and four tocotrienols
They differ in saturation of side chain
Tocopherols studied more extensively, especially alpha tocopherol
Sources include wheat germ, nuts (especially almonds & walnuts), seeds (especially sunflower & pumpkin), whole grains, green leafy vegetables, kiwifruit, vegetable oils, shrimp, fortified cereals
Also from some animal sources (fish-liver oil)
Dairy has no significant amounts of vitamin E

31. How vitamin E is measured in supplements
RDA = 15 mg
Content of supplements usually given in international units (IU) rather than mg
IUs reflect the biological activity of E
Natural has higher activity than synthetic forms
Supplements often have a variety of forms
For natural vit E (d-alpha-tocopherol)
To find mg, multiply IU by 0.67
To find IU, multiply mg by 1.49
For synthetic vit E (dl-alpha-tocopherol)
To find mg, multiply IU by 0.45
To find IU, multiply mg by 2.22

32. Functions of vitamin E Antioxidant
Protects lipids from becoming rancid, particularly the PUFAs in cell membranes
Free radicals destabilize the membranes and alter cell function
Vit E donates or receives electrons to render PUFA stable
Thought to prevent plaque formation by keeping LDL from oxidation
Thought to prevent cataracts by preventing oxidative damage in lens
This clouds lens with precipitates of oxidized proteins
Also aids in vit. A absorption, iron metabolism, & helps maintain nervous & immune functions
Many other claims made but not thoroughly documented

33. Vitamin E deficiency Populations at risk include: Premature infants
Mom doesn’t transfer E to baby till end of term
Premie’s RBCs can burst from oxidative damage
Also have high oxygen needs due to premie lungs
Supplements & formulas for premies are high in E
Smokers
Smoke destroys E in lungs
Mega-dose supplements don’t correct this
People on low fat diets or with fat malabsorption
Fat is needed to absorb vitamin E

34. Too much vitamin E Stored in fat, not in liver
Upper limit is 1000 mg/day of alpha-tocopherol supplement
Interferes with vit. K’s clotting mechanism
This leads to hemorrhage, including stroke
Prolonged bloody nose may be first symptom
Especially a problem for those on aspirin, Plavix, warfarin, or other blood-thinning medication
Can also cause nausea, gas, and diarrhea

35. Fat-soluble: Vitamin K (quinone)
Found in plants, plant oils, fish oils, and animal products
Also made by gut bacteria
These yield about 10% of vit K requirement
Three forms:
Phylloquinone
K1, from plants
Menaquinone
K2, mostly from gut bacteria, natto
Menadione
synthetic form in supplements
twice as biologically active as other forms

36. Functions of vit K
It is a cofactor for reactions involving the addition of CO2 to proteins
This enables the carboxylated protein to bind to calcium
In blood clotting:
Vit. K1 gives several proteins calcium-binding ability (factors 2, 7, 9, 10)
This enables conversion of fibrinogen to fibrin (the clot)
In bone-building:
Vit. K2 gives three proteins (osteocalcin) the ability to bind to calcium
Inhibits calcification in vessels

37. Vitamin K deficiency Very little stored, and can be excreted in urine, so deficiency can build up quickly
Vit. K1
Deficiency causes blood thinning and bleeding problems
An injured newborn does not have full complement of gut bacteria
Therefore does not make much K1
Vit. K injections given
Other ways deficiency can develop:
Antibiotic use destroys gut bacteria
Fat malabsorption can cause deficiency
Old people who often have a poor diet without vegetables
Vit. K2
Deficiency causes bone thinning, calcification of soft tissues

38. The water-soluble vitamins & choline
Must ingest them regularly
Excess ends up in urine or stool
Most are not stored
Except B12
Easily lost when food cooked in water
Best preserved by stir-frying, steaming, and microwaving

39. Absorption and storage of water-soluble vitamins
Broken down from their active coenzyme forms into free vitamins in the stomach and SI
Absorption occurs in SI
Fairly high bioavailability
50-90% absorbed
Transported to liver by the hepatic portal vein
Then distributed to tissues
B12 can be stored there
Re-made into active coenzyme form in cells

40. The 8 B-Complex Vitamins
They often co-occur in the same foods and are interdependent because they function in the same processes
All are involved in cell respiration (metabolism) to make ATP
They act as coenzymes

41. The B-Vitamins: B1 - Thiamine
Needed for cell respiration
In coenzyme form, thiamine pyrophosphate (TPP) participates in reactions where CO2 is released (especially in Krebs cycle)
Also used to make RNA and DNA
Essential for nerve function
Sources: nutritional yeast, sesame seeds, sunflower seeds, pork, pistachios, fish, pecans, peanuts, enriched cereals, milk, organ meat
RDA: Men – 1.2 mg, women – 1.1 mg

42. Thiamin deficiency At risk of deficiency: Deficiency causes beriberi
elderly & low income, high alcohol intake
Deficiency causes beriberi
Two forms, wet & dry
Dry form affects nerves & muscles
weight loss & weakness
emotional disturbances, confusion
Tingling, paresthesias, & irritability
Loss of tendon reflexes
Difficulty walking, paralysis of lower legs
Wernicke's encephalopathy (weakness & pain in the limbs, irregular heartbeat, and swelling of tissues)
Wet form affects heart & circulatory system
can cause heart failure

43. The B Vitamins: B2 - Riboflavin
Riboflavin, especially the coenzyme forms (FAD and FMN) are used for:
cell respiration to make ATP
breakdown of fatty acids
Metabolism of some vitamins and minerals
Support of glutathione peroxidase enzyme
RDA Men-1.3 mg, Women – 1.1 mg
Sources: Yeast, liver, almonds, cheese, fish, sesame seeds, sundried tomatoes, fortified cereals, enriched grains, eggs, milk, nuts

44. Riboflavin deficiency
Deficiency can develop after two months on a low riboflavin diet
Deficiency causes ariboflavinosis
Cracks in the lips and corners of mouth (cheilosis)
High sensitivity to sunlight
Eye disorders
Inflammation of the tongue
Seborrheic dermatitis (around genitals and the mouth)
Sore throat and swelling of mouth and throat
Confusion

45. The B-Vitamins: B3 - Niacin
Two active coenzyme forms:
Nicotinic acid
Nicotinamide
Needed for:
cell respiration to make ATP
As NAD or NADP
metabolism of fat and alcohol
manufacturing lipid, DNA, RNA, and hormones
Used in treatment of addictions and heart disease
Increases HDL
Sources: poultry, fish, meat, nuts, eggs, and milk products
Amino acid tryptophan can be converted to niacin
RDA of niacin depends on amount of tryptophan' in the diet and the efficiency of tryptophan to niacin conversion
The conversion factor is 60 mg tryptophan to 1 mg niacin, which is referred to as 1 niacin equivalent
RDA for men = 16 NE, women = 14 NE

46. Peeling, redness, scaling, and hardening of skin on sun-exposed areas
Niacin deficiency
High risk:
Corn and sorghum based diet
Carcinoid syndrome
Hartnup disease
Taking isoniazid for TB
Deficiency of niacin (and/or deficiency of tryptophan) causes pellagra
The four ‘D’s - dermatitis, diarrhea, dementia, and death
Skin effects seen especially where sun hits and is hyperpigmented and crusty
Tongue is also inflamed and red
Aggression, Insomnia, Weakness
Carcinoid syndrome (flushing, diarrhea, bronchoconstriction, heart problems) from carcinoid tumor secreting too much serotonin
Hartnup’s disease (poor absorption of tryptophan)
Peeling, redness, scaling, and hardening of skin on sun-exposed areas

47. Too much niacin
UL is 35 mg
Only an issue with nicotinic acid form
Side effects include headache, itching, and increased blood flow to skin from vessel dilation
(called niacin flush)
Especially an issue when over 100 mg consumed in a day
GI tract and liver damage are possible
Megadoses are sometimes used in CVD treatment

48. The B-Vitamins: B5 Pantothenic Acid
Needed for cell respiration
Especially for production of coenzyme A
It activates fatty acids so they can release energy
Also used in fatty acid synthesis
Needed to make amino acids, cholesterol, hemoglobin, phospholipids, neurotransmitters, ketones, and antibodies
Adequate intake (AI) is 5 mg/day
Plentiful in foods
Sources include sunflower seeds, peanuts, organ meats, fatty fish, shellfish, yeast, egg yolks, avocado, spinach, broccoli, mushrooms, and dairy

49. Pantothenic acid deficiency
Deficiency likely is rare
But can happen in alcoholics or others with very poor diet
Can result in acne, slow metabolism, edgy nerves, tingling sensations
Pantothenic acid deficiency could possibly be involved in allergies
B5 is needed for production of adrenal hormones
Cortisol prevents histamine release, which causes allergic symptoms
No upper level set; no toxicity

50. The B-Vitamins: B6 - Pyridoxine
Three natural forms in food:
pyridoxine, pyridoxamine, and pyridoxal
The active derivative, pyridoxal 5`-phosphate (PLP), is the most important metabolically active coenzyme form
Used for over 100 reactions 
Needed for :
metabolism of amino acids and lipids
manufacture of neurotransmitters and hemoglobin
production of lecithin
gluconeogenesis
also is a diuretic
Sources: Beans, nuts, eggs, meats, fish, grains
The B-Vitamins: B6 - Pyridoxine
RDA : Men-1.7 mg, women-1.3 mg

51. Intertrigo: rash that develops in skin folds
Vitamin B6 deficiency
Risk of deficiency with meds, including isoniazid, corticosteroids, anticonvulsants, oral contraceptives, and others
Co-occurs with B2, B3, zinc deficiencies
Because B6 is involved with hemoglobin production, deficiency affects many body systems
Deficiency may lead to anemia, depression, sleepiness, seizures, seborrheic dermatitis, intertrigo, sores in mouth, high blood pressure, water retention, weak, numb, & tingly legs
Also elevated levels of homocysteine (high levels are associated with greater heart attack and stroke risk)
seborrheic dermatitis: scaly, flaky, itchy, & red skin affecting the scalp, face, & torso
Intertrigo: rash that develops in skin folds

52. Too much vitamin B6
Intake of more than 1000 mg/day is associated with peripheral sensory neuropathy
Includes:
Difficulty walking
Tingling in hands and feet
Numbness in limbs
Damage to nerves may be reversible, but damage to ganglia is not
500 mg supplements are available online and in health food stores; these far exceed the upper limit of 100 mg per day

53. The B-Vitamins: B7 - Biotin
Needed for cell respiration
As a cofactor for some carboxylase enzymes
Plays a role in gluconeogenesis
Important in metabolism of lipids, proteins & carbohydrates & synthesis of fatty acids
Adequate intake is 30 mcg per day
The bacteria in your gut make some
But unclear how much is absorbed
Probably don’t need a lot in your diet
Most foods have some
Plentiful in protein-rich foods such as egg yolks, peanuts, and cheese
The B-Vitamins: B7 - Biotin
Biotin enhances the strength of skin, nails, and hair

54. Biotin deficiency Deficiency is seen in Deficiency symptoms include:
Chronic anticonvulsant therapy
Long-term antibiotic therapy
Colon surgery (when parts removed)
Excessive raw egg white consumption
Egg whites contain high levels of avidin, a protein that binds biotin strongly
Cooking decreases avidin by 60%
Inborn error of metabolism
Smoking leads to marginal deficiency
Deficiency symptoms include:
Hair loss
Seborrheic dermatitis and eczema
Inflammation of eyelid &/or conjunctiva
Seizures, ataxia, & paresthesia
Anorexia, nausea, & vomiting
Depression & lassitude

55. B-Vitamins: B9 – Folate (& folic acid)
Needed for methylation
Addition of single carbon groups
As coenzymes, help form DNA and metabolize amino acids and their derivatives (such as homocysteine)
Necessary for normal cell division, especially during pregnancy and infancy, times of rapid growth
Used in production of red blood cells
Excellent sources of dietary folate include vegetables such as romaine lettuce, spinach, asparagus, turnip greens, mustard greens, parsley, collard greens, broccoli, cauliflower, beets, and lentils. Liver is also a concentrated source

56. Vitamin B9 terminology Folate Folic acid
the various tetrahydrofolates (THF) naturally found in food
THFs are converted to 5-methyl-folate, the active form that can perform methylation
Some foods already have methylfolate
Folic acid
The oxidized synthetic form in dietary supplements and food fortification
This form must first be converted to THF form in the liver
The enzyme that does this (dihydrofolate reductase, DHFR) has low activity
When combined with a high intake of folic acid from fortified foods or supplements, it may result in unnatural levels of unmetabolized folic acid in the blood (more about this problem later)

57. Folate metabolic cycle (methylation)
Folate is involved in the methylation cycle
One of the most important metabolic pathways!
Methyl group from methylfolate is used to methylate vitamin B12
B12 then methyates homocysteine to make methionine
Prevents homocysteine build-up associated with CVD
Many important products are made from this cycle!
Folate metabolic cycle (methylation)
MTHFR
THF
DHFR
Folic acid

58. Why is methylation so important?
During development, it is important that genes are turned on and off at the right times
Methyl groups from food are “epigenetic factors” that bind to DNA and silence genes (turn them off)
Folate, other B vitamins, and SAM-e (S-Adenosyl methionine) are key donators of methyl groups
Diets high in these nutrients can rapidly alter gene expression, especially during early development

59. The epigenome is so important!
Both mice and people have a gene called agouti
When a mouse's agouti gene is completely unmethylated the mouse:
has a yellow coat color
is obese
Is prone to diabetes and cancer
When the agouti gene is methylated (as in normal mice) the coat color is brown and the mouse has a low disease risk.
This fat yellow mouse and skinny brown mouse are genetically identical.
Skinny brown has methylated agouti gene

60. We know that a human mother's diet is also important in shaping the epigenome
Folate deficiency in pregnant women can lead to neural tube defects
Spina bifida
Anencephaly (missing brain)
Or other birth defects
Cleft palate
Can also impair growth
Folic acid supplementation (from 1 month before conception through 1st trimester) decreases risk of neural tube defects (1 in every 1000 births ) by up to 70%

61. Preventing neural tube defects
A specially formulated vitamin & mineral supplement with folic acid is recommended during pregnancy
Has folic acid, not folate
More bioavailable
1 mcg from food = 0.6 mcg folic acid
Probably more important to supplement before pregnancy
Neural tube closes within first 28 days
Most women not aware they are pregnant till after a month or two
Before 1998, most women did not have adequate daily intake
220 mcg vs recommended 400 mcg

62. Folate deficiency & megaloblastic anemia
In early stages of RBC synthesis, immature cells can’t divide because they can’t form new DNA for lack of folate
But they can make protein & grow
They remain in large form called megaloblast
Condition is megaloblastic anemia or folic acid macrocytosis
Since not mature, few circulate
Blood has poor oxygen capacity
Anemia symptoms develop
RBCs are irregular, oval, or teardrop shapes
Neutrophils have hypersegmented nuclei

63. Folic acid deficiency
Excessive alcohol consumption & poor diet leads to deficiency
Older people may be deficient because:
Lack of teeth
Poverty
Not eating vegetables
Pregnancy can lead to deficiency
Mild deficiency can cause fatigue, gray hair, mouth sores, swollen tongue
In 1998 the FDA mandated that bread, cereal, and other grain products be fortified with folic acid
Approved 0.7 mg/lb masa corn flour in April of 2016

64. Neural tube defects decreased after fortifying food, but now concerns about getting too much folic acid!
High intake associated with cancer
May stimulate the growth of established tumors
Fortification of foods in several countries (including US) was followed by increases in rates of colon & prostate cancers
The presence of unmetabolized folic acid in the blood is associated with decreased natural killer cytotoxicity
natural killer cells play a role in tumor cell destruction
It masks vitamin B12 deficiency in the elderly
It prevents an early warning sign of B12 deficiency, macrocytosis
>400 mcg/day associated with cognitive decline with B12 deficiency
Studies found anemia & cognitive decline in elderly with high intake

65. High folic acid intake may be a risk for those with MTHFR mutations
MTHFR helps convert folic acid into folate
At least 45% of people in US have one copy of a mutated MTHFR gene that decreases this conversion up to 30%
40% of Hispanics, Italians, and northern Chinese are homozygous for C677T
This decreases gene function up to 70%
Double heterozygotes (C677T & A1298C) have 50% loss of function
Increases risk for:
HEART DISEASE AND DIABETES
ANXIETY AND DEPRESSION
MISCARRIAGES
FATIGUE
FIBROMYALGIA
CERVICAL DYSPLASIA
CANCER
and more

66. MTHFR SNPs may be involved in:
Spina bifida
Scoliosis
Down’s syndrome
Marfan syndome
Cleft palate
Fetal alcohol syndome (alcohol decreases B9, affects facial shape and intelligence)
Limb length inequality
Horseshoe kidney (they are connected)
Arnold chiari malformation (cerebellum hangs into neck)
Autism spectrum (1 out of 50 kids, boys 4x as often)
Congenital heart malformations such as hole between ventricles
Tongue tie
Turner’s syndrome
Kleinfelter’s syndome
Gastroschisis (neural tube is closed, but intestine develops outside the body wall)

67. What might be done for MTHFR mutation
Get tested? ~45% of are heterozygous!
Avoid enriched bread, macaroni, dry cereals—any food fortified with folic acid
Avoid regular supplements with folic acid
Make sure that your multi-vitamin or B-complex has these forms:
5-methyl folate
Methylated B12 (methylcobalamin &/or hydroxycobalamin)
Riboflavin (vitamin B2) in form of coenzyme FAD
B2 has to be in form of FAD (as a coenzyme) for MTHFR to work
T4 thyroxine regulates B2 conversion to FAD
We used to think that T3 was the only active form of thyroxine
So if thyroid is dysfunctional, MTHFR does not work well, even if you have a normal MTHFR genotype
There have been problems with overmethylation with this advice, so seek a doctor’s recommendation first.

68. One more B-Vitamin: B12 – Cobalamin
Methylcobalamin is most active form
Cyanocobalamin is in most supplements
It’s only found in animal foods
& it is the only vitamin containing a mineral (cobalt)
RDA = 2.4 mcg
Functions:
Converts folate to active coenzyme forms for DNA synthesis and other reactions
Important in methylation cycle to keep homocysteine levels low
Maintains myelin sheath around neurons
Necessary for cell respiration
Needed for production of blood cells and proteins
Is seaweed a good source of B12?
Its B12 may be from symbiotic bacteria or tiny crustaceans

69. Absorption of B12 is complex!
Two items needed:
Salivary glands & gastric mucosa produce R-binder
Parietal cells in stomach release intrinsic factor
In stomach:
HCl & pepsin release B12 from proteins in food when food is digested
The B12 then binds with R-binder
In small intestine:
Trypsin (a protease) releases B12 from the R-binder
B12 links with intrinsic factor
In ileum the B12-intrinsic factor complex is absorbed into blood and binds to transport protein transcobalamin II
It goes to tissues and to the liver for storage

70. If any step of absorption fails…
Absorption can drop to 1-2%
Can be stored in liver, so it takes many months for deficiency symptoms to show
Takes a lot to catch up! May have to bypass digestion….
Monthly injections of B12 or
Nasal B12 gels
Mega-doses of supplements (300X RDA) can provide enough that it will absorb by simple diffusion
Severe deficiencies seen in:
Older people – they don’t make enough intrinsic factor
Vegans (definitely need to supplement with B12)
Breast-fed babies of vegan mothers can have diminished brain growth, degeneration of spinal cord, and poor intellectual development

71. Vitamin B12 deficiency
Risk of deficiency also in those with fishworm disease, those with pernicious anemia, and those taking certain drugs (PPIs, H2 receptor blockers, metformin)
Deficiency results in macrocytic anemia, elevated homocysteine, peripheral neuropathy, memory loss and other cognitive deficits
Initial symptoms of nerve damage include impaired reflexes, irregular muscle contractions, & paresthesias
Deficiency can also cause red, painful tongue, patchy hyperpigmentation
Deficiency can also cause symptoms of mania and psychosis
In rare extreme cases, paralysis can result

72. Pernicious anemia and B12 deficiency as an autoimmune problem affecting 2% of the elderly
An autoimmune disease that destroys stomach cells that produce intrinsic factor and gastric acid
Vitamin B12 not absorbed
Characterized by:
Macrocytic anemia
Sore mouth
Depression & apathy
Back pain
Irreversible nerve damage with peripheral neuropathy
Weakness & paralysis
Death from heart failure

73. Water soluble: Vitamins C
Important in wound healing and in formation of collagen
Builds connective tissue, bone, teeth, tendons, vessels
It’s a cofactor for several enzymes
Helps synthesize carnitine, which transports fatty acids into mitochondria
helps form serotonin & norepinephrine
Important as an antioxidant!
Also reactivates vit E after it donates e-
Best sources include citrus and other fruits, peppers, broccoli, green leafy vegetables, tomatoes, cabbage
Water soluble: Vitamins C

74. More functions of vitamin C
Immune function
Vitamin C protects phagocytes from oxidants (oxygen radicals) that they make during the respiratory burst
This is the increase in cell respiration they need in order to do phagocytosis
Vitamin C also promotes the proliferation (multiplying) of white blood cells
It does not prevent colds, but it has been shown to shorten the duration of colds
Absorption of iron
It keeps iron in its most absorbable form
Anemics should eat it at meals
Those with hemochromatosis should not!

75. Vitamin C deficiency
SCURVY is a deficiency of Vitamin C: Weakness, anemia, bruising, bleeding gums, poor wound healing, and loose teeth
Can occur as early as 3 months without it in diet
Bleeding gums, tooth loss, bruising, and scaly skin
Skin and blood vessels weaken and wounds will not heal
Recognized in the 1700s in sailors
Dr. James Lind figured out that sailors could eat citrus fruit to correct the symptoms
Sailors were called “limeys”

76. Infantile scurvy comprises most cases
found almost exclusively in 8-14 month olds fed on pasteurized or boiled milk preparations
heating the milk disrupts vitamin C
Symptoms appear after 4-10 months deficiency
Bones are affected as well
Causes osteopenia
Other changes in bones show up on X-rays
Most cases of scurvy today are in infants (& occasionally elderly with poor diets)
The identification of radio-dense lines at the metaphysis, metaphyseal fractures, osseous beaks, epiphyseal displacements, & diaphyseal periostitis allows an accurate diagnosis of scurvy

77. Too much vitamin C Too much from food not usually a problem
Excess ends up in urine
Especially after 100 mg/day
But supplements can have high dosages
As more ingested, absorption decreases
To 50% if 1000 mg eaten
To 20% if 6000 mg eaten
Over 2000 mg can cause diarrhea and stomach inflammation
Men who supplement with C were found to have significantly greater risk of kidney stones

78. Choline – Essential nutrient
Cell membranes
a precursor of phospholipids
phosphatidylcholine, lecithin, is about 50% of the body’s phospholipids
Betaine
important methylation compound; it converts homocysteine.
has choline as a precursor.
Preventing birth defects
Involved in DNA formation during development
Babies born to women with low choline have 4X more defects
Nerve function, brain devel’pm’t
Part of acetylcholine
Sphingomyelin in myelin sheath is choline-containing phospholipid
Levels are high in amniotic fluid
Choline deficiency in pregnancy leads to poor brain development, learning ability, and memory
Lipid transport
A component of lipoproteins
Body can’t transport lipids, so lipids build up in the liver
Can cause scarring & liver dysfunction

79. Where to get choline In many foods
Soybeans, egg yolks, beef, cauliflower, almonds, & peanuts are good sources
They also use lecithin as a food additive
Adequate intake:
Men 550 mg
Women 425 mg
Too much (UL 3.5 g/day) can cause fishy body odor & low blood pressure
Where to get choline
Choline is also made by the body as long as folate and the amino acid methionine are available. However, this process can deplete the body’s folate .

80. Vitamin P? No, it’s not Prozac!
Refers to flavonoids, a group of compounds from plants
The term Vitamin P is rarely used now, but it was popular in the 1950s
Now not considered to be a vitamin
But flavonoids work together with vitamin C to maintain integrity of vessels
Will study them further in Phytochemicals lecture
The term Vitamin P has been used for:
Flavonoids, referred to as Vitamin P from the mid-1930s to early 1950s
Fluoxetine (Prozac), euphemistically referred to as Vitamin P, an SSRI used for depression and various mental disorders
Paroxetine (Paxil), euphemistically referred to as Vitamin P, an SSRI used for depression and anxiety disorders
Prolintane, an NDRI stimulant