to d or not to d that is the question? vitamin d deficiency in australia

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Vitamin D:To D or not to D that is the

question?

Military Health Symposium 2013Steven Boyages and Kellie Bilinski

The University of Sydney



Overview

• Vitamin D status, recommendations and disease prevention

• Aims• Methods• Results • Outcome and signifance



Health benefits of vitamin D

• Low 25(OH)D levels linked to – Osteoporosis and osteopenia– Cancer– Diabetes– Cardiovascular disease– Autoimmune disease– Multiple sclerosis– Respiratory Illness– Mental Health



Optimal serum 25(OH)D Serum 25(OH)D, nmol/L 15 20 25 28 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145

Adapted from Garland CF, Baggerly CA. www.grassrootshealth.org



Vitamin D intake recommendations

*Recommendations based on maintaining serum vitamin D > 75 nmol/L (30ng/ml)

Recognition that individuals who are obese or on certain medications be give 2-3 times more vitamin D

40 IU = 1 µg

Age NHMRC IOM US Endo Society*

0-1 200 400 10001-18 200 600 100019-49 200 600 1500-200050-69 400 600 1500-200070 and over 600 800 1500-2000



Aims of study

1. Investigate vitamin D status in a large cohort of individuals residing in NSW

2. Determine the effect of patient setting, gender, season, remoteness, socioeconomic status, latitude and longitude on vitamin D level



Adequate vitamin D statusVitamin D (nmol/L*)Conventional guidelines

Newer recommendations+

Severe Deficiency <12.5

Moderate deficiency 12.5-25

Mild deficiency 25-50 <50

Insufficiency 50-75

Sufficiency >50 >75

*2.5 nmol/L = 1 ng/ml

+Bischoff Ferrari, AJCN 2006



Australian StudiesNo. of subjects

Latitude (0S) Mean 25(OH)D

Prevalence (%) Ref.

<28 nmol/L <50 nmol/L

Overall

VIC 861 38 - 7.2 30.0 Pasco 2001

SE QLD 414 28 69.1 8.0 23.4 McGrath 2001

Winter

SE QLD 28 - 40.5 McGrath 2001

VIC 861 38 59.1 11.3 43.2 Pasco 2001

VIC 287 38 17.6 60.3 Pasco 2004

TAS 404 43 36.2 ~7.4 50.7 Van der Mei 2007

QLD/VIC/TAS

1669 28-43 67.0/75.5/ 51.1

7.1/7.9/ 13.0

40.5/37.4/ 67.3

Van der Mei 2007 b (pooled analysis)



Season and vitamin D status• Previously assumed enough vitamin D

synthesised and stored for winter requirements • Half life of vitamin D 1-2 months• Submariner study showed mean 25(OH)D levels

declined from 78nmol/L to 48 nmol/L in 2 months in absence of sunlight (P < 0.0001). Diet included fortified milk and bread

• Other studies show between 40% and 80% reduction

Dlugos 1995; Veith 1999



4697

31131 25(OH)D assays1 July 2008 and 30 July 2010

Primary test, complete data available for gender, age, patient setting, date of test, postcode**, known breast cancer case, 25(OH)D ≤400 nmol/L

Sample type

10839 13979

Diagnostic referralOutpatientPrivate outpatientEmergency

InpatientPrivate hospital patientPublic hospital patientPrivate patient

29516

24819Yes

680618012Female Male

62016251Summer Winter

61216245Autumn Spring

1615

QC sampleResearchMiscellaneousUnknown

* *Matched to ARIA, SEIFA, Latitude, Longitude



DemographicsPatient setting No. (%)Outpatient 13979 (56.3)Inpatient 10839 (43.7)Gender

Female 18012 (72.5)Male 6806 (27.4)Season

Summer 6251 (25.2) Autumn 6245(25.2)Winter 6201 (25.0)Spring 6121 (24.7)

Rural and remoteness index No. (%)

Major city 16101 (67.3)

Inner regional 3363 (14.1)Outer regional 3730 (15.6)Remote 446 (1.9)Very remote 281 (1.2)IRSD*

Quintile 1 7507 (31.4)

Quintile 2 4659 (19.9)

Quintile 3 6152 (27.2)

Quintile 4 1944 (8.1)

Quintile 5 3296 (13.8)*Index of relative socioeconomic disadvantage



Mean 25(OH)D by gender

January

February

March AprilMay

JuneJuly

AugustSept

October

November

December

40.0

45.0

50.0

55.0

60.0

65.0

70.0

75.0 74.0

45.1

65.5

43.2

Male

Female

45% re-duction

by June

P<.001

37% reduction

by June



Mean 25(OH)D by patient setting

January

February

March

AprilMay

JuneJuly

August

Sept

October

November

Decem

berTo

tal40.0

45.0

50.0

55.0

60.0

65.0

70.0 70.2

44.9

63.4

42.9

Ambulatory sub-ject

Inpatient

P<.001



January

February

March AprilMay

JuneJuly

AugustSept

October

November

December

40.0

45.0

50.0

55.0

60.0

65.0

70.0

75.0

80.0 79.1

48.6

60.4

42.6

Ambulatory MaleAmbulatory FemaleInpatient MaleInpatient Female

Supporting Women with Breast Cancer Today and Every Day

Mean 25(OH)D by gender and patient setting



Mean 25(OH)D by age group

January

Febr...

Marc

hApril

May

June

July

August

Sept

Oct

Nove...

Dece...

40.0

45.0

50.0

55.0

60.0

65.0

70.0

75.0

80.0

*77.0

65.6

40.7

*61.2

<2020-3940-5960-79≥80

*P<.001



Mean 25(OH)D by remoteness

Majo

r cities

Inner Regio

nal

Outer Regio

nal

Remote Australi

a

Very Remote Austr

alia

01020304050607080

50

*71*66

Ambulatory MaleAmbulatory FemaleInpatient maleInpatient Female

*P<.05



Vitamin D status by gender and season

10%26%

34%

31%

Female Summer

7%21%

32%

40%

Male Summer

18%

37%27%

18%Male Spring

55%

21%

37%27%

15%

Female Spring

Severely Deficient

Deficient

Insufficient

Sufficient

58%

35%

28%



18%

35%30%

16%

Ambulatory subject Spring

12%

27%

30%

30%

Inpatients Summer

23%

39%

24%

14%

Inpatients Spring

Vitamin D status by patient setting by season

6%22%

36%

36%

Ambulatory subject Summer

Severely Deficient

Deficient

Insufficient

Sufficient

54%

62%

39%

28%



Vitamin D status forfemales from a major city by age

group in spring

Inpatient aged ≥80

Severely De-ficiency

Deficient Insufficient Sufficient0%

5%

10%

15%

20%

25%

30%

35%

40%

Ambulatory Subject

Deficient

Severely De-ficiency

Deficient Insufficient Sufficient

Inpatient

20-29 years 30-49 years 80 years and over

68.8%62.5%

Deficient



Vitamin D status in ambulatory females by

socioeconomic status (IRSD)

*Index of relative socioeconomic disadvantage

Severely De-ficient


5%

10%

15%

20%

25%

30%

35%

40%

SummerIRSD 1,2

IRSD 9,10

Severely De-ficient


5%

10%

15%

20%

25%

30%

35%

40%

Spring

38.6 vs 21.2

63.0 vs 51.8



Regression Model• Serum 25(OH)D controlled for gender, patient

setting, season, age category, remoteness from capital city, socioeconomic disadvantage.

• Overall regression model explained 31.8% of the variance (p<0.001)

• Models stratified by gender and patient setting explained between 26.3 (inpatient females and 33.1% (ambulatory females) of variance

• No effect of latitude or longitude



Regression model (overall) 95% CIInpatient -7.1 -8.0-(-6.3)Female -3.9 -4.7-(-3.1)

Season

Summer 15.6 14.6-16.6Autumn 13.9 13.0-15.0Winter 3.8 2.8-4.9

Age category

<20 7.7 6.1-9.340-59 3.0 1.8-4.260-79 2.7 1.6-3.8≥80 1.3 0.1-2.5

ARIA 95% CIInner regional 5.2 4.0-6.3Outer regional 8.8 7.4-10.2Remote 13.1 8.8-17.5Very remote 17.4 13.3-21.6

IRSD

3,4 5.9 4.7-7.25,6 4.8 3.8-5.87,8 5.1 3.6-6.69,10 7.9 6.6-9.1

*all P<.001



Strengths & Limitations

• Size of study, diverse population, ability to control for month of blood draw, age, ARIA, IRSD, latitude and longitude

• Non-random sample, inability to control for other factors that effect vitamin D such as skin pigmentation, body weight, sunlight exposure, sun protection habits



Conclusion

• High prevalence of deficiency in all seasons but highest in spring

• There is a marked seasonal reduction that continues into spring

• Particular groups are more at risk of vitamin D deficiency – young women residing in major city from lower SES

• Protective factors include living in rural areas, being male and from a higher SES



Health Implications• Public health messages required to

address high prevalence of vitamin D deficiency

• Australians are not adequately supplementing - suitable guidelines are required

• Implications regarding frequency and timing of testing



AcknowledgementsWestmead Breast Cancer Institute Vitamin D Research Group

John Boyages, (Supervisor, Oncologist, BCI)

Steven Boyages (Supervisor, Endocrinologist, CETI)

Colin Dunstan (Animal Biologist, ANZAC)

Rebecca Mason (Physiologist, Sydney University)

Peter Talbot (Dietitian, Westmead Hospital)

Elisabeth Black (Director of Research, BCI)

Institute of Clinical Pathology and Medical Research

Gary Ma (ICPMR)

Table 1. Mean plasma 25(OH)D levels and baseline characteristics for cases and controls.

Umhau JC, George DT, Heaney RP, Lewis MD, et al. (2013) Low Vitamin D Status and Suicide: A Case-Control Study of Active Duty Military Service Members. PLoS ONE 8(1): e51543. doi:10.1371/journal.pone.0051543http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051543

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051543

Table 2. Results of the conditional logistic regression analysis including covariates.



Figure 1. Plot of the computed odds ratios (OR) for the 8 octiles of 25(OH)D concentration, locating each at the mid-point of the respective octiles.



Figure 2. Plot of the odds ratio for suicide for the top seven octiles, relative to the lowest octile.



The subjects with serum concentrations of 25-hydroxyvitamin D [25(OH)D] < 40 nmol/L (n = 24) had significantly (P = 0.004) more days of absence from duty due to respiratory infections

(median: 4; quartile 1–quartile 3: 2–6) than did controls (2; 0–4; incide...

Laaksi I et al. Am J Clin Nutr 2007;86:714-717

©2007 by American Society for Nutrition

to d or not to d that is the question? vitamin d deficiency in australia

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