Module 9

• Fat-Soluble Vitamins


  • More difficult eliminating excess (compared to water-soluble vitamins)
  • Don't dissolve in watery substances
  • Body stores extra, particularly in liver and adipose tissue
  • Overtime they can accumulate and cause toxicity
• Fat-soluble vitamins require bile and chylomicrons for absorption
• Decreased risk of deficiency, but increased risk of toxicity
• International Units (IUs)


  • In the past, most vitamins expressed as IU
  • Today most replaced with more precise mg or ug
  • Food composition tables still often list IU values for fat-soluble vitamins

  
• Active forms of Vitamin A (retinoids)

  • Retinol = storage form of vitamin A (often stored as retinyl esters)
  • Retinal = vision
  • Retinoic Acid = cell differentiation

  
• Carotenoids


  Plants contain carotenoids (e.g., beta-carotene); provitamins / vitamin precursors -- the body must convert it to the active form(s)
• Vitamin A in the Digestive Tract


  1. Both pre-formed vitamin A and carotenoids are bound to proteins in foods

  2. Must be released by pepsin

  3. In small intestine the released retinol and carotenoids combine with bile acids and other fat-soluble food components to form micelles

  4. Absorption pre-formed vitA 70-90%

  5. Pro-vitamin carotenoids not as well absorbed (and absorption decreases as intake increases)

  6. Transported from intestine in chylomicrons for delivery to body tissues (bone marrow, blood cells, spleen, muscles, kidney, liver)

  7. Liver is main storage site (~90%); to move from liver stores to tissues, retinol must be bound to retinol binding protein (RBP)

  8. Body can make retinal and retinoic acid forms from retinol and carotenoids in diet

  
• Retinol


  Circulates in blood
• Retinal


  Important for vision

  
• Retinoic acid


  Made from retinol or retinal, affects gene expression and is responsible for Vitamin A's role in cell differentiation, growth, and reproduction

  
• Conversion of retinol to retinal is reversible, but pathway from retinal to retinoic acid is not

  
• Beta-carotene


  • Converted into retinal in intestinal mucosa and liver
  • Cleaving beta-carotene yields two molecules of retinal
  • 12mg beta-carotene yields 1mg retinol

  
• Vitamin A and Vision

  • Retina (light-sensitive area in ea. eye) contains rods and cones
  • Rods enable adaptation to see in poorly lit environments
  • Cones responsible for color vision and function in well-lit environments
  • Retinol needed for proper function (converted to retinal)

  
• Vitamin A: Retinol and Retinal

  1. Rhodopsin is composed of opsin and vitamin A (retinal)

  2. If vitamin A (retinal) levels are low, body cannot re-form rhodopsin, and night blindness results

  3. Eyes so sensitive to vitamin A levels that one injection can relieve this night blindness in minutes

  4. Takes a certain amount of time for rod cells to react to dim light [after a sudden and dramatic reduction in light intensity]

  5. Night blindness - some retinal that splits away from rod cells is destroyed; to replace, the rods remove some retinol from bloodstream and convert it to retinal

  6. If retinol is unavailable à night blindness (inability to see in dim light)

  
• Differentiation


  • Cells change in structure and function to become specialized
  • Vitamin A affects this through its effect on gene expression (can turn on or off production of certain proteins that regulate functions within cells and throughout the body)
  • Vitamin A can determine what type of cell an undifferentiated cell will become

  
• Vitamin A: Retinoic Acid


  • Functions: Growth & Development
  • Role in cell differentiation necessary for production, maturation, and maintenance of epithelial tissue
  • Form protective tissues that line the body (incl. skin and linings of digestive, respiratory, and reproductive tracts)
  • Functions: Immune Function
  • If microorganisms breach first barrier (epithelial cells), immune cells attack invaders
  • Plays a role in production and activity of white blood cells
  • Vitamin A controls gene expression that induces differentiation of immature immune system cells into mature wbc (phagocytes, lymphocytes)
  • Certain white blood cells produce antibodies that help destroy infectious agents (e.g., bacteria)
  • Functions: Bone Growth & Development
  • Bones constantly remodeled
  • Vitamin A helps produce bone cells needed for growth [required for bone remodeling]
  • Too much Vitamin A also results in bone loss and increased risk fracture

  
• Vitamin A is stable when heated but may be destroyed by exposure to light and oxygen
• Retinol activity equivalent (RAE)


  Provides Vitamin A intake from all sources

  
• Vitamin A Deficiency


  • Threat to health, sight, lives of millions children in developing world
  • Why are children more susceptible than adults?
  • Can be caused by insufficient intakes of vitamin A, fat, protein...
  • Not common in developed world; status depends on liver stores & protein intake
• Vitamin A Toxicity


  • Symptoms acute toxicity: nausea, vomiting, headache, dizziness, blurred vision, lack of muscle coordination
  • Symptoms chronic toxicity: weight loss, muscle/joint pain, liver damage (main site of storage), visual defects, dry scaling lips, skin rashes, bone abnormalities
• Vitamin A DRI UL 18+ yrs

  3000 ug/day
• Vitamin A is toxic at extremely high doses; typically from supplements
• Vitamin D


  • Produced in skin (Vitamin D3) from sun exposure
  • Absorbed from diet (vitamin D2)

  
• Sources of Vitamin D

  • Fatty fish, cod liver oil, egg yolk, butter, dietary supplements
• 25-OH vitamin D


  Blood levels used to determine vitamin D status
• Vitamin D Metabolism


  1. UVB action on 7 dehydrocholesterol to form D3 --> enters circulation (chylomicrons, lymph, liver)

  2. Can be stored in fat or go to liver

  3. In liver, hydroxylated to 25-OH-D (inactive)

  4. Circulation to kidney

  5. Hydroxylated to 1,25 dihydroxycholecalciferol (active hormone)

  6. Active Vitamin D production tightly regulates Ca and P levels via parathyroid hormone

  
• Calcium must be carefully regulated because of important role it plays in muscle contraction
• Other Functions of Vitamin D

  • Regulating neuromuscular and immune function
  • Reducing inflammation
  • Reduce risk heart disease, cancer, diabetes, multiple sclerosis, asthma, depression
  • Much research is needed to clarify its role in chronic disease prevention

  
• Groups at risk of Vitamin D deficiency


  • Infants
  • Children
  • Males
  • Females
  • Pregnancy
  • Lactation
• Vitamin D Deficiency


  • Those south of 33rd parallel and who are outdoors btw 10am-3pm (when sunlight is more intense) often obtain enough sun exposure to synthesize vitamin D during most of the yr
  • Those living north of 33rd parallel, angle of winter sun is such that sun's rays must pass through more of atmosphere than at other times of yr
• Vitamin D Deficiency


  • A nutrient of public health concern
  • Many North Americans do not consume enough Vitamin D (nearly half have low blood levels); more likely to be deficient if: darker skin tone, overweight, electronic media / games >4h/day, drinking milk less than once/wk
  • Elite athletes also at risk; some research suggests relationship between deficiency and injury risk
• Vitamin D Deficiency (Rickets)


  • By the 17th century, some people in parts of northern Europe learned that exposing children to sunlight or giving fish liver oil prevented [or treated] rickets
  • By 19th century, scientists learned that rickets can be prevented by sunlight exposure, vitamin D supplements, and vitamin D-rich foods
  • While severe rickets is uncommon, recent increase in no. cases in infants / toddlers
  • Human breast milk insufficient vitamin D
  • Young children most likely to develop rickets: breastfed, dark skin, minimal sunlight exposure, little to no vitD intake
  • Recommendation: breastfed -- 400IU supplement / day; formula fed -- ensure formula fortified with vitamin D
  • Consume 400 IU/day through adolescence

  
• Vitamin D Deficiency (Osteomalacia)


  • Adults form vitamin D deficiency
  • "soft bones" (bend and break easily; esp. hips, spine)
  • Normal amount collagen but lower-than-normal amount calcium
  • Can precipitate or exacerbate osteoporosis
  • Highest risk: confined indoors or almost fully covered when outside (religious, cultural reasons); kidney, liver, intestinal diseases
• Skeletal disorder characterized by low bone strength predisposing a person to increased risk of fracture
• Most common sites of osteoporosis: hip, lumbar spine, wrist
• Vitamin D Deficiency with Age


  • With age, production of 7-dehydrocholesterol in skin declines, and conversion of pre-vitamin to active vitamin D in kidneys decreases
  • More likely to develop vitamin D deficiency
  • Older adults also at risk for bone fractures
• Not all older adults are deficient in vitamin D
• Formula fed


  Ensure formula fortified with vitamin D
• Consume 400 IU/day through adolescence


  Vitamin D
• Osteomalacia


  • Adults form vitamin D deficiency
  • Soft bones (bend and break easily; esp. hips, spine)
  • Normal amount collagen but lower-than-normal amount calcium
  • Can precipitate or exacerbate osteoporosis