vitamin d

vitamin D-binding protein binds to

vitamin D-binding protein binds to calcitriol and transports it in plasma to other organs

• Melanoma is

• Melanoma is a malignant tumor of melanocytes.

rickets

• Rickets causes softening of bones in children which can potentially lead to bone deformity (e.g., leg bowing) and fractures. • Predominant cause is vitamin D deficiency. • Can also be caused by low calcium intake.

tactile epithelial cells

: location—basal layer; attached to sensory nerve endings

ancestral sources of vitamin d

Ancestral humans source of vitamin D • Given the fact that breast milk does not contain adequate levels of vitamin D, humans have evolved to consistently get vitamin D from the SUN. • Throughout evolution, humans have spent a lot of time outside exposed to the sun, often without clothing. • Humans of all ethnicities have the least amount of melanin when they are newborns and infants; this enables infants to increase the use of sunlight UVB to synthesize vitamin D. • Also, women have a reduction in their levels of melanin during pregnancy which enables them to more efficiently manufacture vitamin D from sun exposure; a woman's vitamin D requirement increases when she is pregnant

B9

B9 (folic acid and folate) Essential to numerous bodily functions • Water soluble vitamin • Involved in synthesis, repair, and methylation of DNA. • Cofactor in numerous biological functions. • Aids rapid cell division and growth, such as in infancy and pregnancy. • Bone marrow maturation. • Red blood cell production. • Development of neural tubes in embryos. 51

B9 (folic acid and folate)

B9 (folic acid and folate) • Folate and folic acid derive their names from the Latin word folium(which means "leaf"). • Important sources of folate are leafy green vegetables (e.g., kale & spinach) & some fruits e.g. oranges. • Folate consumed in the diet is metabolized in the liver to produce bioactive metabolites.

B9 (folic acid and folate)

B9 (folic acid and folate) • People who regularly consume folate will have 500-20,000 µg of folate in body stores. • With complete lack of dietary folate intake, it can take months before these stores are depleted.

B9 (folic acid and folate)

B9 (folic acid and folate) • The terms folic acid and folate are often used interchangeably for the water-soluble B9 vitamin. • Folic acid occurs rarely in foods or the human body but is the form most often used in vitamin supplements and fortified foods and is easily bioavailable. • Naturally occurring folates exist in many chemical forms. • Folates are found in plant foods as well as in metabolically active forms in the human body.

behavioral factors that reduce vitamin d production in the skin

Behavioral factors that reduce Vitamin D production in the skin • Sunscreen • Concealing clothing • Spending much of the day inside • Excessive use of soap on areas of skin exposed to sun • Choice to live in an area with low number of sunny days out of each year

benefits of pigmentation

Benefits of pigmentation • Pigmentation (melanin) serves to regulate the effects of UV radiation in the contents of cutaneous blood vessels located in the dermis. • High skin melanin levels contribute to darker skin color which protects against sunburn, skin cancer, and the destruction of nutrients (e.g., folic acid) in the skin.

Calcidiol to calcitriol

Calcidiol to calcitriol • Circulating calcidiol is then converted in the kidneys into calcitriol (1,25-dihydroxycholecalciferol = 1,25-dihydroxyvitamin D3), the biologically active form of vitamin D which functions as a hormone.

calcitriol binds to

Calcitriol binds to vitamin D-binding protein, a carrier protein in the plasma, that transports calcitriol to various target organs.

calcium

Calcium • Normal vitamin D levels are essential for proper absorption of dietary calcium

cause of osteomalacia

Cause of osteomalacia • Deficiency in vitamin D • Diminished sun exposure to skin resulted in diminished vitamin D production in skin. • Very low intake of vitamin D in the diet since woman is lactose intolerant and does not drink milk and does not take Vitamin D supplement

Cholecalciferol to calcidiol

Cholecalciferol to calcidiol • cholecalciferol synthesized in the skin is carried into bloodstream to the liver, where it is converted into prohormone calcidiol (25-hydroxycholecalciferol = 25-hydroxyvitamin D3)

clines

Clines • Genetic analysis of alleles undergoing clinal traits demonstrates corresponding clinal variation in allele frequencies. • Our genotype, and consequently our phenotype, are determined by the position of our indigenous origin on a multitude of intersecting clines. • For example in the eastern hemisphere, some clines, e.g., skin melanin, go north-south while other clines, e.g., blood type B span east-west.

clines

Clines • The continuous variation in human traits on gradients which vary in orientation means that there are no boundaries, geographical or genetic, which can be used to assign individuals to particular races....there are no races, only clines. • Similarly, intrapopulation and interpopulation variation in disease risk tends to be clinal and not racial. • Clinal variation can also be demonstrated within and between ethnolinguistic groups

clines

Clines • With many human characteristics/traits there is a continuous geographical gradient (cline) of a trait rather than discontinuous variation. • Because of the north-south clines that exist for skin melanin, there is often a gradual and progressive change along a clinal gradient rather than discontinuous variation. • Hence, the designation of race based on skin melanin is erroneous...there are no races, but only clines which demonstrate a continuous spectrum of variation within Homo sapiens.

dendritic cells

Dendritic cells: location—stratum spinosum; part of immune system; macrophage-like

dietary sources of calcium

Dietary sources of calcium • Beans e.g. soy products • Nuts and seeds • Whole grains • Leafy greens, broccoli • Dairy products

epidermis cell types

Epidermis cell types • Keratinocytes: most common cell type in epidermis and are full of keratin • Melanocytes: location—basal layer; manufacture and secrete pigment • Tactile epithelial cells: location—basal layer; attached to sensory nerve endings Dendritic cells: location—stratum spinosum; part of immune system; macrophage-like

female melanin levels

Female melanin levels • Females have lighter skin than males, most likely to facilitate greater vitamin D3production to aid in calcium absorption for proper bone deposition.

female melanin levels

Female melanin levels • Maternal melanin levels drop during pregnancy so she can more efficiently manufacture vitamin D on her skin to aid in calcium absorption. • Maternal calcium needs increase during pregnancy and lactation because the mother must provide enough calcium for fetal and neonatal skeleton development. • Infants also have lower levels of melanin than older children and adults which enables them to produce more vitamin D in their skin. • A tradeoff is that the lighter skin results in more depletion of folate in blood.

folate continued

Folate • Folate deficiency and neural tube defects are more prevalent among people with less skin pigmentation. • There is an increased incidence of neural tube defects with maternal tanning bed use, which exposes the skin to direct UV light resulting in folate photolysis.

folate

Folate • This important vitamin undergoes photolysis when exposed to UV light, which can contribute to a folate deficiency. • The increased skin pigmentation protects the folate from photolysis in the presence of UV light. • Folate deficiency is less prevalent among people of African descent.

folate deficiency

Folate deficiency • A serum folate of 3 µg/L or lower indicates deficiency. • An erythrocyte folate level of 140 µg/L or lower indicates inadequate folate status. • Folate deficiency is treated with supplemental oral folate of 400 to 1000 µg per day.

folate deficiency

Folate deficiency • Macrocytic anemia • Impairment of DNA synthesis and repair • Peripheral neuropathy • Neural tube defects (e.g., spina bifida and anencephaly) in developing embryos • Increased risk for cleft lip and palate

folate deficiency affect on pattern forming genes

Folate deficiency affect on pattern forming genes • Neural tubes close in the early weeks post conception. • Folate deficiency in embryos before neural tube closure increases the likelihood of neural tube defects e.g., spina bifida and anencephaly. • It appears that this nutritional deficiency in the embryo may affect the expression or action of pattern-forming genes. • Folic acid supplement is recommended for all pregnant women.

folate deficiency during pregnancy increases risk of

Folate deficiency during pregnancy increases risk of • preterm delivery • infant low birth weight • fetal growth retardation • increased homocysteine level in the blood, which may lead to spontaneous abortion and pregnancy complications

folic acid for pregnant and lactating women

Folic acid for pregnant and lactating women • All pregnant women are recommended to take a daily oral supplement of folic acid prior to conception and throughout their pregnancy and lactation. • Women who get 400 micrograms (0.4 milligrams) daily prior to conception and during early pregnancy reduce the risk by 70% that their baby will be born with a serious neural tube defect (a birth defect involving incomplete development of the brain and spinal cord). 58

Genetic Evidence for Convergent Evolution of Light Skin in Europeans and East Asians through different SNP mutations

Genetic Evidence for Convergent Evolution of Light Skin in Europeans and East Asians through different SNP mutations • The SNP (single nucleotide polymorphism) genetic mutations leading to light skin, are different among East Asians and Europeans. • The two groups likely experienced a similar selective pressure due to settlement in northern latitudes. • Norton, et al (2006). Molecular Biology and Evolution 24 (3): 710-22.

Genetic Variation at the MC1R Locus and the Time since Loss of Human Body Hair

Genetic Variation at the MC1R Locus and the Time since Loss of Human Body Hair • Around 1.2 million years ago it is estimated that the skin of Homo erectus was dark and mainly hairless and this continued in Homofor the next 1.1 million years until 100,000 years ago when the first Homo sapiens started migrating out of Africa. • Rogers, Iltis, & Wooding (2004). Current Anthropology 45: 105-8.

hair loss

Hair loss • It is suggested that over time human hair disappeared to allow better heat dissipation through sweating. Jablonski, Jablonski, & Chaplin (2000). Journal of human evolution 39 (1): 57- 106. • However, other evolutionary biologists believe that hair loss was triggered by sexual selection.

human migration and skin color

Human migration and skin color • 100,000 to 70,000 years ago, as populations began to migrate, the level of skin melanin typically decreased proportionally to the distance North a population migrated, resulting in a range of skin tones from the equator up to more northern latitudes. • Under conditions of less UV light exposure in northern latitudes, there was less photodestruction of folate. • In addition, lighter skin is able to generate more vitamin D (cholecalciferol) than darker skin given the same UV light exposure, resulting in a health benefit and selective advantage in reduced sunlight.

human skin pigmentation as an adaptation to uv radiation

Human skin pigmentation as an adaptation to UV radiation • Skin pigmentation reduces folate depletion by reducing the exposure to UV from sunlight. • Jablonski, N. G.; Chaplin, G. (2010). Proceedings of the National Academy of Sciences 107: 8962-8.

increase in epidermal permeability barrier

Increase in epidermal permeability barrier • Essential protective functions of the skin, including the permeability barrier and the antimicrobial barrier, reside in the stratum corneum. • The loss of body hair likely triggered an increase in genetic change related to the stratum corneum as natural selection favored mutations that protect this essential barrier.

increase in epidermal permeability barrier

Increase in epidermal permeability barrier • The skin tone grew darker to increase the epidermal permeability barrier. • Elias et al. (2010). American Journal of Human Biology 22(4):526-537.

Influence of developmental experience and evolutionary history on susceptibility to sunburn

Influence of developmental experience and evolutionary history on susceptibility to sunburn • Susceptibility to sunburn is modified by ancestral evolutionary origin (skin color) and past sun exposure (suntan).

It is believed by many evolutionary biologists that the selective pressure for lighter skin color in northern latitudes arose from

It is believed by many evolutionary biologists that the selective pressure for lighter skin color in northern latitudes arose from the need to maximize vitamin D production in the skin in areas of relatively low ultraviolet B availability.

keratinocytes

Keratinocytes: most common cell type in epidermis and are full of keratin

layers of epidermis stratum basale

Layers of Epidermis Stratum basale • Melanocytes—spider shaped melanocytes make up 10-25% of the cells in stratum basale • Melanocytes make melanin and transport it through its spider shaped cells process to nearby keratinocytes

light skin covered by dark hair

Light skin covered by dark hair • Based on an examination of the variation in MC1R nucleotide sequences (Rogers, Iltis, & Wooding, 2004. Current Anthropology 45:105-8.), it is estimated that roughly five million years ago, after the evolutionary separation of chimpanzees and humans, the common ancestors of humans had light skin that was covered by dark hair. • Today, our closest extant relative, the chimpanzee, continues to have light skin covered by dense body hair.

Long term exposure to different amounts of sunlight at different latitudes has created

Long term exposure to different amounts of sunlight at different latitudes has created a spectrum of human skin colors influenced by the variation in the amount and type of melanin in the skin, with an almost linear relationship between latitude of population origin and skin melanin levels

melanin and uv radiation

Melanin & UV radiation • Darker skinned people have darker melanin and more pigment in each melanocyte. • In all but the darkest skinned people, melanocytes respond to ultraviolet radiation by increasing production of melanin and increasing its transfer to keratinocytes, the protective response which results in a suntan.

melanin in skin

Melanin in skin • Sensitivity of skin to UV radiation is influenced by its level of melanin. • Most people with light skin can increase their level of melanin by moderate exposure to sun over days or weeks which stimulates increased output of melanocytes (suntan) which is an example of physiological plasticity.

melanin level as outcome of demographic history

Melanin level as outcome of demographic history • Humans with highest levels of melanin tend to have ancestors who originated from regions of the world (e.g., equatorial latitudes) where they have been exposed to large amounts of UV light. • Humans with low levels of melanin tend to have ancestors who originated from regions of world north of the equator exposed to lower levels of UV light.

Melanocytes are

Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin.

melanocytes

Melanocytes: location—basal layer; manufacture and secrete pigment

melanoma is common in

Melanoma is particularly common among light skinned humans living in sunny climates • High rates of incidence in Australia, New Zealand, North America, and parts of Europe

modest sun exposure and enviro and behavioral mismatches

Modest sun exposure & environmental and behavioral matches • Humans from latitudes from all over the world evolved to have modest direct exposure of sun on their skin. • Adequate vitamin D production is essential for proper bone development. • People with moderate tans have higher vitamin D levels. • People with moderate tans have lower rates of breast cancer and prostate cancer. • A balance (match between evolutionary history, and contemporary environment and behavior) between enough sun and not to-much sun exposure is important. • This balance is a match between evolutionary history and contemporary environment and behavior.

natural selection of melanin level

Natural selection of melanin level • Natural selection favors high pigmentation in areas of high sun and high ultraviolet exposure to protect against ultra-violet light skin damage and skin cancer. • Natural selection favors decreased pigmentation in areas of low sunlight and ultraviolet exposure to increase vitamin D synthesis.

Oral intake of Vitamin D • 1-70 years of age: • 71+ years of age: • Pregnant/lactating: • Some nutritionalists are recommending

Oral intake of Vitamin D • 1-70 years of age: 600 IU/day (15 µg/ day) • 71+ years of age: 800 IU/day (20 µg/ day) • Pregnant/lactating: 600 IU/day (15 µg/ day) • Some nutritionalists are recommending 1,000-2,000 IU/day

pigmentation

Pigmentation • Pigmentation is an adaptation to the presence of UV light that contributes to fitness by influencing vitamin D3 and folate levels in the body.

selective forces on pigmentation

Selective forces on pigmentation • Pigmentation decreases when vitamin D3production needs are increased. • Pigmentation increases to protect against UV damage to folate in blood as well as skin cell nuclei. • Both vitamin D and folate are necessary for reproductive success so for good health there should be a balance between the requirements for these two nutrients.

Serum 25-hydroxyvitamin D3

Serum 25-hydroxyvitamin D3 • Serum 25-hydroxyvitamin D3 levels of 30 to 50 ng/ml are now considered to be in the desirable range by many dieticians and physicians. • Some consider 40 to 80 ng/ml to be the desirable range.

skin melanin, vitamin D and folic acid

Skin melanin, vitamin D and folic acid • Melanin in skin is inversely related to vitamin D production. • Melanin in skin is inversely related to folic acid destruction in blood. • High melanin levels is related to high folic acid blood levels and low vitamin D production from UVB. • Low melanin levels is related to low folic acid blood levels and high vitamin D production from UVB.

Skin pigmentation effect on vitamin D3 and folate

Skin pigmentation effect on vitamin D3 and folate • decreased pigmentation leads to increased UV light exposure which leads to increased vitamin D3 production • decreased pigmentation leads to increased UV light exposure which leads to increased folate depletion in blood

spina bifida

Spina bifida • Spina bifida in fetus and newborn is associated with pregnant mothers who have low levels of serum folate. • This woman's serum folate was checked and found to be well below normal levels.

too little sun exposure and vitamin d deficiency

To little sun exposure and vitamin D deficiency • People of all skin color types who consistently use sunscreen, wear concealing clothing, and/or stay inside much of the day are at increased risk for vitamin D deficiency • There is an epidemic of vitamin D deficiency in the USA among all ethnicities • A recent study in the USA on levels of Vitamin D deficiency shows that African-Americans have prevalence rates of 52-76%, 18-50% in Latinos, and 8-31% in European-Americans

Too little sun exposure, vitamin D deficiency and environmental & behavioral mismatches

Too little sun exposure, vitamin D deficiency and environmental & behavioral mismatches • Humans from latitudes from all over the world evolved to have modest direct exposure of sun on their skin.

Too little sun exposure, vitamin D deficiency and environmental & behavioral mismatches can lead to what diseases

Too little sun exposure, vitamin D deficiency and environmental & behavioral mismatches • Males and females with low levels of vitamin D can develop rickets (children) or adult osteomalacia. • Males and females with low levels of vitamin D have higher rates of autoimmune disease. • Males and females with low levels of vitamin D have higher rates of autism. • Men and women with low levels of vitamin D have higher rates of hypertension.

Too little sun exposure, vitamin D deficiency and environmental & behavioral mismatches can lead to what disesases continued

Too little sun exposure, vitamin D deficiency and environmental & behavioral mismatches • Men with low levels of Vitamin D have higher rates of prostate cancer. • Women with low levels of Vitamin D have higher rates of breast cancer. • Women with low levels of Vitamin D have higher rates of bacterial vaginosis. • Women with low levels of Vitamin D have higher rates of cesarean section.

too much sun exposure and enviro and behavioral mismatches

Too much sun exposure and environmental & behavioral mismatches • Humans from latitudes from all over the world evolved to have modest direct exposure of sun on their skin. • Adequate vitamin D production is essential for proper bone development. • However, to much sun exposure (and tanning salon exposure) especially in lighter skinned people increases their risk for skin cancer. • This is an example of an environmental mismatch and a behavioral mismatch. 38

Too much sun exposure and environmental & behavioral mismatches

Too much sun exposure and environmental & behavioral mismatches • Humans from latitudes from all over the world evolved to have modest direct exposure of sun on their skin. • Adequate Vitamin D production is essential for proper bone development. • However, too much sun exposure (and tanning salon exposure) especially in lighter skinned people increases their risk for skin cancer; this is an example of an environmental mismatch and a behavioral mismatch.

vitamin d

Vitamin D • People with dark skin require up to 10 times more exposure to sunlight than people with light skin to produce the same amount of Vitamin D. • Darker skinned people who live in more northern latitudes than their ancestors, are at risk for Vitamin D deficiency.

Vitamin D (cholecalciferol) production

Vitamin D (cholecalciferol) production • Cholecalciferol is produced in the deep epidermis in the stratum spinosum and stratum basale. • The melanin in the keratinocytes blocks the penetration of UV into the epidermis and shields the cell nuclei from incoming UV radiation. • Inverse relationship between level of melanin in skin and ability of skin to manufacture vitamin D at a given UV exposure.

vitamin d in infants

Vitamin D in infants • Adequate Vitamin D is required for growth and development of infants • Breast milk is a poor source of vitamin D • Human infants have evolved spending enough time outside to provide them with regular skin exposure to sunlight to produce vitamin D. • Compared to adults, newborns and infants have lower levels of melanin to maximize their ability to utilize sunlight for vitamin D production.

vitamin d levels inversely related to bone fractures in girls

Vitamin D levels inversely related to bone fractures in girls • Over 9,000 girls 9 to 15 years of age were followed over a 7 year period. • 4% of these girls developed a bone stress fracture and 90% of these girls participated in at least an hour a day of high-impact physical activity • Girls in the group with the 20% highest intake of vitamin D were 52% less likely to develop a fracture than girls in the group with the 20% lowest intake of vitamin D. • Sonneville et. al., Archives of Pediatrics and Adolescent Medicine, March 5, 2012

vitamin d production and skin melanin

Vitamin D production & skin melanin • People with dark skin require up to 10 times more exposure to sunlight than people with light skin to produce the same amount of Vitamin D. • Darker skinned people who live in more northern latitudes than is represented in their evolutionary history, are at risk for Vitamin D deficiency. • A recent study in the USA on levels of Vitamin D deficiency shows that African-Americans have prevalence rates of 52-76%, 18-50% in Latinos, and 8-31% in European-Americans.

cholecalciferol synthesized

in skin

calcitriol (1,25-dihydroxyvitamin D3) formed in

kidney

calcidiol (25-hydroxyvitamin D3) formed in

liver