Vitamin D supplementation of professionally active adults

Transcription

1 Vitamin D supplementation of professionally active adults VITAMIN D MINIMUM, MAXIMUM, OPTIMUM FRIDAY, SEPTEMBER 22 ND 2017 Samantha Kimball, PhD, MLT Research Director Pure North S Energy Foundation

2

3

4 The Pure North program Pure North is a not-for-profit organization seeking to help Canadians feel better and live longer. The Pure North program effectively works to prevent chronic disease through research-based nutrition and education and does so in a cost conscious manner. Simply put, we care about the health of Canadians and endeavour to help people access support and resources they need to live healthier lives. Since 2007 more than 50,000 Canadians have benefited from Pure North s support of a tailored and measured approach to improve their overall health and wellness.

5 Targeting serum 25(OH)D levels 1. Naturally achieved through sun exposure Mean = 115 nmol/l 2. Suppression of compensatory mechanism: PTH Mean = 120 nmol/l 3. Support of Lactation Mean = 120 nmol/l *also level associated with 60% reduced risk of preterm labour Heaney, Toward a physiological referent for the vitamin D requirement. J Endocrinol Invest 37(11): ; Luxwolda et al., Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l. Brit J Nutr 108: ; Ginde et al Defining vitamin D status by secondary hyperparathyroidism in the US population J Endocrinol Invest 35:42-8; Wagner et al., Post-hoc analysis of vitamin D status and reduced risk of preterm birth in 2 vitamin D pregnancy cohorts compared with South Carolina March of Dimes rates. J Steroid Biochem Mol Bio 155:

6 Vitamin D: An Absolute Requirement for Healthy Living < 25 nmol/l nmol/l nmol/l nmol/l > 250nmol/L SEVERELY DEFICIENT: Risk of rickets 75% greater risk of colon cancer DEFICIENT: Increased calcium loss from bones Poor wound healing Increased muscle, joint and back pain Increased inflammation Increased risk of diabetes, schizophrenia, migraines, depression, autoimmune disease, allergies, preterm labour, preeclampsia, SGA SUBOPTIMAL: Twice the risk of heart attack Increased incidence of hypertension 3-fold increased risk of MS OPTIMAL: 50% reduced risk breast cancer, risk of solid cancers Slowing of cancer growth in patients with cancer Reduced risk of osteoporosis, autoimmunity, inflammation, depression, CVD, cancers, etc. INCREASED RISK OF TOXICITY: >500 nmol/l Institute of Functional Medicine

7 Vitamin D dose-response is not linear Ekwaru, The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers. PLOS One 9(11):e

8 BMI-based dosing BMI Range Underweight Normal Overweight Obese Vitamin D required to achieve serum 25(OH)D of 150 nmol/l 5,000 9,000 IU/d 9,000-11,000 IU/d 12,000 14,000 IU/d 19,000 24,000 IU/d Ekwaru, The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers. PLOS One 9(11):e

9 Safety of High doses Not a single case of toxicity in 10 years! Kimball et al., Evaluation of vitamin D3 intakes up to 15,000 IU/d and serum 25-hydroxyvitamin D concentrations up to 300 nmol/l on calcium metabolism. Dermato- Endocrinology 9(1):e

10 Vitamin D & Health Outcomes EVIDENCE FROM THE PURE NORTH PROGRAM

11 Quality of Life Cross-sectional (Chao et al.) Vitamin D levels >125 nmol/l were associated with higher quality of life scores Participants with 25(OH)D >125 nmol/l were less likely to report problems with mobility (39%), usual activities (30%), pain and discomfort (26%) or any other problem (37%) Longitudinal analysis (Ekwaru et al.) Average 25(OH)D were raised from 95 nmol/l at baseline to 130 nmol/l at one year. Time in the program and increased 25(OH)D levels both positively influenced of QOL scores. Participants reported significant fewer problems with mobility, usual activities, pain/discomfort, depression/anxiety and any problem, after 6 months and at 1 year. For every 25 nmol/l increase in 25(OH)D, QOL increased by score units. Quality adjusted life years (QALY), the amount of time spent in full health, increased by units with each 25 nmol/l increase in 25(OH)D levels. Overall, QALY gain of years in full health of 4.4 days of full health gained. Chao et al., Vitamin D and health-related quality of life in a community sample of older Canadians. Qual Life Res 23(9): ; Ekwaru et al., The Effectiveness of a Preventive Health Program and Vitamin D Supplementation in Improving Quality of Life (QOL) of Older Canadians. Qual Life Res 25(3):

12 25-OH vitamin D (pmol/l) Follow-up status Preventing & treating type 2 diabetes mellitus % of prediabetic reverted to normoglycemia at one year (total sample n=1,014) Diabetic Prediabetic Normal Normal Prediabetic Diabetic 48% at 2 years reverted to normoglycemia (n= 338) Baseline status Kimball et al. Effect of vitamin and mineral supplementation on glycemic status: results from a community-based program. Diab Res Care Pract (SUBMITTED)

13 Meta-analysis: Vitamin D treatment for type 2 diabetes 24 studies met inclusion criteria. Mean Effect: -0.3% for HbA1c, -4.9 mg/dl for FPG, for HOMA-IR with significant increase in 25(OH)D (overall 42 nmol/l increase). Vitamin D supplementation, a minimum dose of 4,000 IU/d, may significantly reduce HbA1c, FPG and HOMA-IR and help to control the glycemic response and improve insulin sensitivity in type 2 diabetic patients. Mirhosseini et al. Effect of improved 25(OH)D on glycemic control in type 2 diabetic patients: A meta-analysis JCEM 102(9):

14 Meta-analysis: Vitamin D in the prevention of type 2 diabetes 26 trials included (n= 3,935) Compared with controls vitamin D supplementation significantly reduced HbA1c level by %, FPG by mmol/l and HOMA-IR level by Vitamin D supplementation was found to improve glycemic measures and insulin sensitivity, and may be useful as a preventive strategy for Type 2 diabetes. Mirhosseini et al. The impact of vitamin D supplementation on glycemic control and insulin resistance in high risk populations for diabetes: A systematic review and meta-analysis of randomized control trials. British Journal of Nutrition (SUBMITTED)

15 Depression & Anxiety Baseline Level of Depression/Anxiety Change at One Year Number (%) Worse Improve No Change Total None 386 (7.1) (92.9) 5448 Slight 154 (4.1) 3017 (79.5) 625 (16.5) 3796 Moderate 36 (2) 1601 (87.8) 187 (10.3) 1824 Severe 3 (0.8) 342 (95.3) 14 (3.9) 359 Extreme (100) Total 579 (5) 5090 (44) 5888 (50.9) Chi-Square p<0.001 Of 11,557 participants, 52.9% were identified as having elevated levels of depression and anxiety at baseline as reported on the EQ-5D. After one year in the program, 44% (n=5,090) of participants who reported any level of depression or anxiety subsequently reported improvement. Of those who reported severe/extreme depression at baseline (n=489), 96.5% reported improvement after one year. At one year mean depression and anxiety scores were significantly improved with large effect sizes (2.2) when serum 25(OH)D levels were above 75 nmol/l. Kimball et al. Database analysis of depression and anxiety in a community sample response to a micronutrient intervention. BMC Psychiatry (SUBMITTED).

16 Thyroid Function & Autoimmunity Serum 25(OH)D >125 nmol/l was associated with 32% reduced risk of elevated anti-thyroid antibodies. Relative Risk (95% CI) based on Serum 25(OH)D, nmol/l [n=11,017] < 125 (n=9,796) 125 (n=1,226) P value* FT3 decrease 1.02 ( ) 0.88 ( ) 0.02 FT4 decrease 1.56 ( ) 0.95 ( ) 0.01 Anti-TPO increase 1.18 ( ) 0.32 ( ) < Anti-TG increase 1.15 ( ) 0.37 ( ) < TSH increase 1.07 ( ) 0.55 ( ) <0.001 TG increase 1.02 ( ) 0.89 ( ) 0.08 hs-crp increase 1.12 ( ) 0.43 ( ) < Follow-up N (%) Anti-TPO Anti-TG Both Baseline Positive Negative Positive Negative Positive Negative Positive 564 (66.8) 280 (33.2) 561 (25.5) 1,636 (74.5) 221 (50.2) 219 (49.8) Negative 27 (1.6) 1,710 (98.4) 44 (2.4) 1,768 (97.6) 3 (0.9) 327 (99.1) Mirhosseini et al. Physiological serum 25(OH)D concentrations are associated with improved thyroid function. Endocrine (SUBMITTED).

17 Hypertension Of 8,155 participants with relevant data, there were 592 participants (7.3%) at baseline considered hypertensive. Of those, 71% were no longer in the hypertensive range at follow-up (12 ± 3 months later). There was a significant negative association between blood pressure and serum 25(OH)D level (systolic BP: coefficient=-0.07, p<0.001, diastolic BP: coefficient=-0.09, p<0.001). In a nested case-control study we compared vitamin D treatment to vitamin D treatment with blood pressure-lowering medications. There was no significant difference between groups. Reduced mean systolic (-18.3 vs mmhg) and diastolic (-12.5 vs mmhg) blood pressure, pulse pressure (-5.8 vs mmhg) and mean arterial pressure (-14.4 vs mmhg) was not significantly different between hypertensive participants who did and did not take BP-lowering medication. Mirhosseini et al. The association between serum 25(OH)D status and blood pressure in participants of a community-based program taking vitamin D supplements. BMC Nutrition (SUBMITTED).

18 Cardiovascular Disease Risk Included 7,393 participants. Improvements were found for all CVD risk factors as well as Framingham and Reynold s risk scores. Regression models revealed a significant impact of vitamin D status, serum 25- hydroxyvitamin D [25(OH)D], on reducing the majority of CVD risk factors whereas vitamin B12 and arachidonic acid: eicosapentaenoic acid [AA:EPA] only influenced HOMA-IR. Optimal 25(OH)D >100 nmol/l was associated with improvements. Kimball et al. Longitudinal analysis of cardiovascular disease risk factors in participants of a preventive health program. Cardiovascular disease risk factor Abdominal Obesity Hypertriglyceridemia Low HDL cholesterol Hyperglycemia Hypertension Metabolic Syndrome Insulin Resistance Prediabetes Diabetes Inflammation (hs-crp 2mg/L) Intermediate Risk - Framingham (10-20%) High Risk - Framingham (>20%) High Risk - Reynold s (>10%) Present at baseline? Present at follow-up? (N (%)) Yes No Yes 1,130 (85.1) 198 (14.9) No 196 (11.6) 1,494 (88.4) Yes 403 (68.3) 187 (31.7) No 322 (13.3) 2,106 (86.7) Yes 314 (66.4) 159 (33.6) No 197 (7.8) 2,348 (92.2) Yes 315 (71.6) 125 (28.4) No 304 (11.8) 2,274 (88.2) Yes 253 (51.6) 237 (48.4) No 211 (8.4) 2,317 (91.6) Yes 270 (66.1) 138 (33.9) No 227 (8.7) 2,383 (91.3) Yes 306 (65.0) 165 (35.0) No 190 (9.7) 1,764 (90.3) Yes 437 (42.6) 589 (57.4) No 170 (8.8) 1,763 (91.2) Yes 139 (68.5) 64 (31.5) No 37 (1.3) 2,719 (98.7) Yes 684 (69.7) 297 (30.3) No 287 (14.1) 1,750 (85.9) Yes 483 (51.5) 455 (48.5) No 448 (21.9) 1,601 (78.1) Yes 420 (71.7) 166 (28.3) No 251 (10.5) 2,150 (89.5) Yes 438 (76.0) 138 (24.0) No 170 (7.4) 2,114 (92.6)

19 Conclusions Vitamin D influences many health outcomes. Targeting 25(OH)D levels is most consistent with biology and may explain inconsistencies in the literature. Optimal levels of 25(OH)D may differ based on those outcomes. CVD: >100 nmol/l HTN: >100 nmol/l Thyroid antibodies: >125 nmol/l Depression: >75 nmol/l HbA1c: >100 nmol/l Quality of Life: >125 nmol/l Optimal levels are higher than 50 nmol/l!