Articles
Year 2019
August 2019
07 August 2019

Vitamin D and Longevity... Revelation and Relevance in 2019 and Beyond

In the last 5 years, there has been many advances in the understanding of the roles and importance of Vitamin D. This invited article serves as a brief update and review and provides a platform for awareness of the Vitamin D adequacy for our personal and patients’ well being as physicians practising in the 21st century.

Vitamin D is not only important for calcium and bone metabolism but also increasingly recognized to play a part in the severity and pathogenetic risk of developing non skeletal pathologies like Rheumatoid Arthritis (RA), Osteoarthritis (OA), cardiovascular diseases and diabetes. In recent years, a growing body of evidence has proposed a broad range of potential extra-skeletal effects of vitamin D. For example, a higher circulating 25(OH)D concentration may facilitate synthesis of cathelicidin, a peptide capable of destroying infectious agents. It also has been suggested that monocytes and/or macrophages are prevented from initiating an innate immune response when serum 25(OH)D concentrations are low. Further, a higher circulating serum 25(OH)D concentration may offer protection against the development of cancer. Taken together, these studies suggest that vitamin D may play a wide role in the pathogenesis of many disorders such as cardiovascular diseases, infectious diseases, autoimmune diseases, and cancer, all of which are important contributors to all-cause mortality.

Vitamin D Deficiency in Sunny Singapore

Vitamin D deficiency is common in Singapore and has been reported in 5 previous studies since 2009, but none have reported the disease associations and treatment outcomes.1-5 We did our own study in 2016 and reported the prevalence, clinical demographics and treatment of 173 patients who underwent Vitamin D testing in our community rheumatology clinic.6

The Results are summarised as below:            

A total of 220 Vitamin D assays were done from August 2015 to Feb 2016 in our clinic. 71% of the tests showed deficient /insufficient Vitamin D levels. 173 patient’s records were retrievable and reviewed. Age Range: 15-87 years. 73.4% were female and 75.6% are Chinese. Percentage of Vitamin D deficiency/ insufficiency by race:  Chinese 68.7%, Malay 87.5%, Indian 72.4%, Others 60%.  Percentage of Vitamin D insufficiency/deficiency by sex: Male – 72.3%; Female 69%.

70% of the patients had Vitamin D levels below normal (<29.9ng/mL). 6 had deficiency (Vitamin D <10ng/mL), the lowest level being 2.5ng/mL. 65.3% of patients with low Vitamin D levels had associated either OA or RA or both.

81% of Vitamin D deficient/insufficiency patients had treatment: 71 had intramuscular Vitamin D3 200,000- 300,000iu followed by oral D3 2000iu/day; 19 received intramuscular Vitamin D3 alone; 18 had oral D3 supplements.

44 patients reviewed had serial Vitamin D levels recorded. 28  showed improvement in Vitamin D levels after treatment from 16.5-35.2ng/mL range to 17.4- 45.4ng/mL.

16 patients had decrease in Vitamin D levels from 19-65.2 ng/mL range to 17.6-45.2ng/mL when they defaulted on vitamin D treatment and supplements.

Conclusions of our study were:

  1. Vitamin D deficiency/insufficiency is still highly prevalent among community patients in Singapore, among all races and age groups.
  2. Vitamin D deficiency/insufficiency is associated with rheumatological conditions like OA and RA.
  3. Treatment of Vitamin D deficiency/insufficiency is advocated and effective.

Association of Vitamin D Deficiency and Mortality

Several large cohort studies have shown that serum 25(OH)D concentrations were inversely associated with all-cause and cause-specific mortality. In particular, vitamin D deficiency [25(OH)D concentration <30 nmol/L] was strongly associated with mortality from all causes, cardiovascular diseases, cancer, and respiratory diseases. In the ESTHER study involving nearly 10,000 German patients, Vitamin D deficiency (serum 25(OH)D concentration <30 nmol/L) was associated with a 40% increased risk of cancer and cardiovascular death.7 In a meta-analysis of 8 cohort studies conducted in Europe and the United States by Schottker et al., they found that compared with the top quintile of serum 25(OH)D concentration, the bottom quintile had HRs for all-cause mortality of 1.54 (95% CI: 1.27, 1.86) and 1.57 (95% CI: 1.26, 1.95) for those aged 60–69 y and 70–79 y, respectively.8

Vitamin D Adequacy and Benefits

High concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations.

A interesting study just published this month involving 2185 Chinese older adults (692 centenarians, 724 nonagenarians, 769 octogenarians with median age: 93 yr) looked at the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ≥80 yr. 38.6% of participants manifested vitamin D deficiency (<30 nmol/L) and 24.9% showed severe deficiency (<25 nmol/L).9

Compared with the lowest age-specific quartile of plasma 25(OH)D, the adjusted HRs for mortality for the second, third, and fourth age-specific quartiles were 0.72 (95% CI: 0.57, 0.90), 0.73 (95% CI: 0.58, 0.93), and 0.61 (95% CI: 0.47, 0.81), respectively. See the figure below: (AQ 1   3.26–29.2 nmol/L; AQ 2 :21.1–39.8 nmol/L; AQ 3:29.3–53.3 nmol/L; AQ4: 41.5–90.7 nmol/L .)

These results are consistent with the data from several cohort studies in which serum 25(OH)D concentration was inversely associated with all-cause mortality independent of frailty, physical activity, and chronic diseases. This study provides convincing evidence that a higher plasma 25-hydroxyvitamin D concentration was associated with a reduced risk of all-cause mortality among Chinese adults aged ≥80 yr! Those with serum Vit D levels above 40nmol/l had the a 40% improved survivor rate at 5 years follow-up! Definitely we can draw some applications into our practice by treating our vitamin D deficient elderly Singaporeans!

Positive Results from Intervention Studies

The analysis of several observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D3 supplementation and 1.04 (0.97 to 1.11) for vitamin D2 supplementation.10

Using prostate cancer as an illustrative example, studies have shown the positive effects of Vitamin D supplementation on prostate specific antigen (PSA) (p < .05), on median survival (p < .05) and showed a significant reduction of vitamin D receptor (VDR) expression (p < .05). Current evidence suggests that vitamin D supplementation should be added in conjunction with standard oncology care. 11

Factors that contribute to Vitamin D Deficiency

Medical conditions like liver and kidney disease, obesity, gastric bypass surgery, age, dark-colored skin, home-bound or indoors work are factors that contribute to vitamin D deficiency. Medications like laxatives, steroids, proton pump inhibitors, cholesterol-lowering drugs, anti-epileptic drugs and anti-TB drugs can contribute to low vitamin levels.

Optimal Vitmain D Levels and Vitamin Supplmentation and Replacement Therapy

I routinely check my patients for serum 25(OH) D levels. Whereas the sufficient Vitamin D level is defined as > 30ng/ml, the optimal 25(OH)D concentrations is defined as >50 nmol/L. As most people are deficient or insufficient in Vitamin D, supplementation and treatment is essential,

  1. By IM injections of Vitamin D3 100,000 iu -200,000iu to boost the levels more quickly as shown our study.6
  2. Weekly liquid Vit D 25,000iu ( D-Cure)
  3. Oral Vit D3 daily – 1000-3000iu/day.
CURRENT VIT D LEVELS TO ACHIEVE THIS LEVEL OF VIT D HOW MUCH SUPPLEMENT PER DAY
0-10 NG/ML 30NG/ML 2000IU
10-20 NG/ML 40NG/ML 3000IU
20-30 NG/ML 40NG/ML 2000IU
30-40 NG/ML 50NG/ML 2500IU

Conclusion:

Given the benefits of optimal Vitamin D levels for bone health, disease prevention and even mortality reduction even in the elderly, it behoves us as physicians to check our patient’s vitamin D levels and initiate treatment and supplementation and patient education and lifestyle changes to bring the patient’s vitamin levels to optimal levels for optimal health!

References:

  1. Hawkins RC. 25-OH Vitamin D3 concentrations in Chinese, Malays, and Indians. Clin Chem 2009;55: 1749-1751.
  2. Zhong YL et al. Clin Kidney J 2012; 5 (4): 303-308
  3. Hawkins R, MD. Total 25-OH Vitamin D Concentrations in Chinese, Malays and Indians. Ann Lab Med. 2013 Mar; 33(2): 156-158.
  4. Ramason R et al. Prevalence of Vitamin D Deficiency in Patients With Hip Fracture Seen in an Orthogeriatric Service in Sunny Singapore. Geriatr Orthop Surg Rehabil.2014 Jun; 5(2): 82-86.
  5. Bi X et al. Prevalence of Vitamin D Deficiency in Singapore: Its Implications to Cardiovascular Risk Factors. PloS ONE 11(1): e0147616.doi:10.1371/journal.pone.0147616
  6. YOON KH, NAVA IMK, CHEONG SK, LIM ML. Medlab Asia 2016 Poster Presentation:High Prevalence of Vitamin D Deficiency among 173 Patients attending a Community Rheumatology Clinic: A Profile of Demographics and Treatment
  7. Ben Schöttker et al.Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study.  The American Journal of Clinical Nutrition, Volume 97, Issue 4, April 2013, Pages 782–793
  8. Schottker et al. Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States.BMJ. 2014 Jun 17;348:g3656. doi: 10.1136/bmj.g3656.
  9. Chen Mao et al.25-Hydroxyvitamin D Concentrations Are Inversely Associated with All-Cause Mortality among a Prospective Cohort of Chinese Adults Aged ≥80 Years . The Journal of Nutrition, Volume 149, Issue 6, June 2019, Pages 1056–1064,https://doi.org/10.1093/jn/nxz041
  10. Chowdhury R et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014 Apr 1;348:g1903. doi: 10.1136/bmj.g1903.
  11. Petrou S et al.Effect of Vitamin D Supplementation in Prostate Cancer: A Systematic Review of Randomized Control Trials.Int J Vitam Nutr Res. 2018 Feb;88(1-2):100-112. doi: 10.1024/0300-9831/a000494. Epub 2019 Apr 30.

A Specialist’s Point of View – Written by Dr Yoon Kam Hon

Dr Yoon Kam Hon is a consultant rheumatologist at El Shaddai Arthritis and Rheumatism Specialist Medical Centre and at Changi General Hospital, Singapore. He has been a clinical teacher in the Faculty of Medicine since 2004.

Dr Yoon completed his Bachelor of Medicine, Bachelor of Surgery in 1991 and subsequently obtained a Master of Medicine (Internal Medicine), Specialist Accreditation in Internal Medicine and Specialist Accreditation in Rheumatology. He is a fellow of the Academy of Medicine, Singapore.

Dr Yoon is a member of the National Arthritis Foundation and a member of the Singapore Society of Immunology, Allergy and Rheumatology. In 2011, he was awarded with the Singapore Health Quality Service Award – Silver Award from SingHealth. Dr Yoon has presented at international conferences and his work has been published in numerous international peer-reviewed journals. His interest includes viscosupplementation for osteoarthritis, use of biologics in autoimmune rheumatic diseases and advance supplements.

El Shaddai Arthritis and Rheumatism Specialist Medical Centre
Tel: 6396 6965
Email: elshaddaiclinic@gmail.com

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