Nathan Billing

Brief overview of dietary sources of vitamin DDefining Vitamin D statusVitamin D in New ZealandBiochemistry of metabolism of vitamin DKey conditions affected by Vitamin D

OsteoporosisInfluenzaCardiovascular diseaseCancer

Supplementation

In Australia but not New Zealand, all table margarines are fortified with vitamin D,

Old-World Primates Humans with UV Canadian Winter Canadian + 25 ug/d Canadian + 100 ug/d0

40

80

120

160

Ser

um

25(

OH

)D

nm

ol/

L

A blood calcidiol (25-hydroxy-vitamin D) level is the accepted way to determine vitamin D nutritional status, and shows considerable

variation.

Primates Humans Canadians 1000 IU 4000 IU

in sun in winter supplement supplement

140 130

4070

100

20 40 60 80 100 120

Serum 25(OH) D nmol/L

Insufficiency

According to Dietitian’s NZ clinical handbook 2010

25OH-vitamin D

<25nmol/L

25-50nmol/L

50-150nmol/L

<250nmol/L

Moderate-severe deficiency

Mild deficiency

Optimal target for bone health

Intoxication reported

1,25OH-vitamin D

65-175pmol/L Interpretation is specific to clinical context

Vitamin D deficiency: an emerging public health problem in Australia1 (all over the world)

Deficiency bone pain, muscle weakness, osteoporosis, falls, fractures1

60% of postmenopausal Australian women with osteoporosis had low serum vitamin D (<30 ng/mL)2*

* International study of 2606 postmenopausal women with osteoporosis, including 204 women from Australia

1. Osteoporosis Australia. Calcium, Vitamin D and Osteoporosis – A Guide for GPs 2nd edn2. Lips P et al. J Int Med 2006; 260:245-254.

New Zealand has one of the highest incidencesof skin cancer in the world.

Vitamin D is not a problem here.

Or is it??

378 men aged >40 years (mean age 57 yrs)

serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L4–17% in Summer0–20% in Winter

92% European dissent

1,606 women aged >55 years (mean age 74 yrs)

serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L20–30% in Summer50–75% in Winter

99.8% of European dissent

Lucas JA, Bolland MJ, Grey AB et al (2005) Determinants of vitamin D status in older women living in a subtropical climate. Osteoporos Int 16:1641–1648

Bolland MJ, Grey AB, Ames RW et al (2006) Determinants of vitamin D status in older men living in a subtropical climate. Osteoporos Int 17:1742–1748

Bolland MJ, Grey AB, Ames RW et al., (2007) The effects of seasonal variation of 25-hydroxyvitamin D and fat mass on a diagnosis of vitamin D sufficiency.

Am J Clin Nutr 86:959–964

These results similar to National nutrition survey 2,946 adults aged over 18 years had a

measurement of 25(OH)D 1

52% of adult women <50 nmol/l45% of adult men <50 nmol/l

1,585 children aged 5–14 years, had a measurement of 25(OH)D 2

4% girls and 3% boys <17.5 nmol/l36% girls and 27% boys <37.5 nmol/l

So despite a warm and sunny climate with high UV exposure in the summer months, many in New Zealand have suboptimal vitamin D status.1. Rockell JE, Green TJ, Skeaff CM et al (2005) Season and ethnicity are determinants of serum 25-hydroxyvitamin D concentrations in New

Zealand children aged 5–14 year. J Nutr 135:2602–2608 2. Rockell JE, Skeaff CM,Williams SM et al (2006) Serum 25-hydroxyvitamin D concentrations of New Zealanders aged 15 years and older.

Osteoporos Int 17:1382–1389

Lower atmospheric ozone concentrations over New Zealand because of the Antarctic ozone hole.

Less polluted air over New Zealand

Sun is slightly closer to the Earth in December than in June.

These contribute to high UV levels and warm climate

Which in turn => Increased skin cancer.

John Cannell and Bruce Hollis, Alternative Medicine Review Volume 13, Number 1 March 2008

HORMONEA messenger produced and secreted by

specific glands or cells within the body of animals.

Transported through the blood stream to designated target organs.

Binds to its specific receptor delivering its message to a specific set of cells.

VITAMINA substance regularly required by the body in

small amounts.The body cannot make vitamins.Must be supplied in diet.

Vitamin D : A Hormone & A Vitamin

Formation of Active Vitamin D

Holick, M.F., 2007. Vitamin D Deficiency. N Engl J Med 357 pp266-81

Season Geographic latitudeTime of dayCloud /fogSun screenAgeing skin Excess skin coverWindow glassIndoor life style

25(OH)D levels are: strongly related to measures of fat mass, moderately related to BMI or body weight, and not related to lean mass.

The inverse relationship between 25(OH)D and fat mass has been attributed to increased sequestration of fat-soluble vitamin D in adipose tissue in obese individuals

Other factors contributing to low levels

the month of blood sample, age, fat mass, and physical activity were significantly related to 25(OH)D in women

month of the blood sample, percentage body fat, serum albumin, and physical activity were significantly related to 25(OH)D

From New Zealand Surveys

Effect of fat Mass on Vitamin D

Research associated Vitamin D to All cause mortalityHeart diseaseDiabetesCancerOsteoporosisAthletic abilityDepression

Vitamin D and Osteoporosis

“Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture”

NIH Consensus Development Panel, JAMA 2001;285:785-795

Osteoporosis

Bone Mineral Density Over the Lifespan

Minimal in healthy young men and premenopausal women

Accelerates at menopause due to estrogen deficiency

Continues throughout life

Increases in old ageInfluenced by other

factors – nutrition Diseases Medications Activity etc

Adapted from Wasnich RD, et al. Osteoporosis: Critique and Practicum. Honolulu, Banyan Press, 1989:179-213Recker R, et al. J Bone Miner Res. 2000;15:1965-73

Vitamin D and Influenza

Vitamin D Effects immunityVitamin D modulates the macrophage response,

preventing the release of excessive inflammatory cytokines and chemokines Hewison M, et al. Molecular and Cellular Endocrinology 2004; 215: 31-38. Helming L, et al. Blood 2005; 106: 4351-4358.

Vitamin D promotes macrophage production of specific surface antigens, the lysosomal enzyme acid phosphatase, and the secretion of H2O2 (which is antimicrobial), but vitamin D deficiency decreases these functions.

Abu-Amer Y, Bar-Shavit Z. Cellular Immunology 1993; 151: 356-368. Cohen MS, et al. Journal of Immunology 1986; 136: 1049-1053.

Vitamin D stimulates genetic expression of antimicrobial peptides, which have broad-spectrum antimicrobial activity and inactivate influenza virus.

Wang TT, et al. Journal of Immunology 2004; 173: 2909-2912. Gombart AF et al, The FASEB Journal 2005; 19: 1067-1077.

Liu PT, et al. 2006; 311: 1770-1773. Reddy KV et al, International Journal of Antimicrobial Agents 2004; 24: 536-547.

Hiemstra PS, et al. Current Pharmaceutical Design 2004; 10: 2891-2905. Daher KA et al, Journal of Virology 1986; 60: 1068-1074.

Influenza is a seasonal illness

Weekly consultation rates for clinically diagnosed fluCannell JJ, Vieth R, Umhau JC,et al. Epidemiol Infect. 2006

(WHO Data)

Remember New Zealand latitude

34–47◦S

Historical studies with cod liver oilIn the 1930’s, Vitamin A was investigated for its

anti-infective properties using Cod liver oil, (which is also abundant in Vitamin D)

Five studies using cod liver oil, (involving over

7,000 subjects), showed that cod liver oil reduced respiratory infections

Cod liver oil given to 185 adults for four months reduced colds by 50%; Holmes AD, et al. Journal of Industrial and Engineering

Chemistry 1932; 24; 1058-1060.

In a five year study, cod liver reduced industrial absenteeism caused by colds and respiratory illness; days of missed work was reduced by 30%. (n=3031)

Homes AD, et al. Industrial Medicine 1936; 5: 359-361.

Vitamin D and Insulin response and Diabetes?

Low serum 25-hydroxyvitamin D (25(OH)D) concentrations have been shown to correlate with impaired glucose tolerance and an increased risk of type 2 diabetes

FoundInsulin sensitivity did improve in these insulin-

resistant women with vitamin D supplementation

Vitamin D and Cancer

Vitamin D sources, metabolites, and mechanisms of actionwith respect to carcinogenesis.

VDR: vitamin D receptor. VDRE: vitamin D response element. RXR: retinoid X receptor

Vitamin D and Cardiovascular disease

How much vitamin D results from sun exposure

Serum 25(OH)D levels indicate the average American gets between 50 and 1000 IU units

5 minutes in a bathing suit in the summer noon day sun provides about 3,000 IU.

Melanin in the skin reduces production of vitamin D by sunlight, and African Americans have much lower 25(OH)D levels than whites

90% of vitamin D is obtained from the sun.

New Zealand Dietary reccomendations

The recommended nutrient intakes or Adequate Intakes (AIs) for vitamin D, which assume minimal exposure to sunlight, are:

5 [micro]g/day (200IU) for infants, children and adults 50 years of age or less;

10 [micro]g/day (400IU) for adults 51-70 years of age

15 [micro]g/day (600IU) for adults >70 years of age

Ministry of Health (NZ), National Health and Medical Research Council. Nutrient Reference Values for Australia and New Zealand.2004

Vitamin D2 vs Vitamin D3

Time course of the rise in serum 25OHD after a single oral dose of 50,000 IU of either cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) to two groups of 10 normal men each

Armas, L. A. G. et al. J Clin Endocrinol Metab 2004;89:5387-5391

Use formulations with sufficient dose:

Ostelin (ergocalciferol 25 µg = D2 1000 IU)

Ostevit D, Blackmores Vitamin D (cholecalciferol =D3 1000 IU)

Ostelin Vitamin D & Calcium (cholecalciferol = D3 500 IU) Doses in calcium and multivitamin preparations too low

for treatment of deficiency Cod liver oil contains vitamin A, which may increase

fracture risk

Dosing Supplementation: 1000 IU per day Moderate-severe deficiency: 3000–5000 IU per day for

6–12 weeks then maintenance. Check blood level at 3 months

Costs approximately 24 cents/day for supplementationANZBMS Med J Aust 2005; 182: 281-285.

Vitamin D supplementation

ToxicityVitamin D is fat soluble, and accumulation

(from diet) in the body can be toxic.

The long-term safe dose of vitamin D is not known, however, 10,000 IU /day is safe in healthy adults

All known cases of vitamin D toxicity have involved intake of or over 40,000 IU/day.

The LD50 in man is unknown – there are no reported deaths from acute toxicity.

Questions/ Discussion

Hollick 2008 link

The 1903 Nobel prize was awarded for the discovery that vitamin D from sunlight could cure cutaneous TB….