Vitamin D and health – the facts

Screen Shot 2017-10-01 at 13.44.46Vitamin D is an oil soluble essential vitamin. Ingestible forms include vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). These are converted to 25-hydroxyvitamin D in the liver then to bioactive calciferol in the kidneys. Calciferol regulates absorption of calcium, magnesium and phosphate from the gut, it modulates the healthy growth and remodeling of bone and has effects on cell growth in other organs. It also has neuromuscular, immune functions and other biological processes which influence by degeneration and inflammation. The serum reference range of 25-hydroxyvitamin D is 75-200 nmol/l (30-80 microg/l).

 

Recommended Daily Amount:

Oral requirements are greater in the winter than the summer. The 2010 RDA is 600 IU for those 1-70 years of age and pregnant or breastfeeding women, and 800 IU (40 Microgram) for those over 71 years of age. There are some reports that overweight individuals require more vit-D as it can be broken down in the peripheral fat. Vitamin D has a half-life of 6 weeks so by 3 months of no sunlight exposure, unless there are high dietary intakes, blood levels will drop to one quarter. This explains the findings from the online micro-nutritional screening, published in the National Cancer Conference Liverpool 2013, that over 70% of people from the UK tested had suboptimal levels of vitamin D and even greater between December to March. Although Vitamin D2 is commonly used in oral supplement, a randomised trial published in 2017 in American Society of Nutrition Journal found that D3 was better at increasing serum 25-hydroxyvitamin D than D2 especially in Asian women. It is often to difficult to ask your doctor to measure blood levels of Vit-D but it is included in online micronutrient test (cancernet.co.uk) which includes all three D2, D3 and 25-hydroxyvitamin D isoforms.

Vitamin D and sunlight:

man-sunVit-D levels are higher amongst those who exercise outdoors regularly as UV-B radiation interacts with the skin to make cholecalciferol from cholesterol. It is estimated that almost 80% of the body’s required vitamin D is produced by the skin. Excess sunlight, particularly associated with sunburn, is the main cause of epithelial skin damage, premature aging and skin cancers and clearly should be avoided. On the other hand, regular sensible sun exposure is the best way to maintain adequate serum vitamin D levels. Epidemiological studies have reported that evaluation of men and women with jobs involving exposures to sunlight were less likely to develop a number of cancers including prostate, kidney and bowel cancer (Luscome, Schwartz). A study from Australia reported that people treated for the skin cancer melanoma who ignored the advice form their doctor to stay out of the sun, actually had a lower risk of the melanoma spreading to another part of the body because they prevented vit-D deficiency.

Vitamin D and health:

Deficiency in children leads to severe bone damage (rickets) and in adults, osteomalcia. These conditions were common amoung Asian communities in the early seventies, who came to the UK from sunnier climates, until supplementation and education programmes where initiated. Unfortunately, although rickets is rare, suboptimal vitamin D levels are still very common in Asian communities. More recently cases in middle class whites have also been reported. Most notably, a 10 year old girl from the Isle of White, who tripped on the pavement in 2012, broke both legs and was found to be profoundly vit-D deficient as her parents always applied total sunblock and protective clothing when outside since birth. Epidemiological studies have shown that 25OHD deficiency is closely associated with a number of common chronic diseases such as cardiovascular diseases, dementia, Parkinson’s disease, other neuropsychiatric disorders and autoimmune diseases (Wang). A recent study has also confirmed that individuals within populations with a lowest serum 25(OH)D concentrations had the highest all-cause mortality rates (Garland). This increased chance of death took into account other factors such as obesity and smoking.

Vitamin D and cancer:

Cancer cells exposed to calciferol in laboratory studies have been shown to slow cancer growth and spread by reducing proliferation, promoting differentiation, inhibiting invasion, preventing loss of adhesion and promoting apoptosis (Chiang). Vit-D has also be shown to interact with the androgen-signalling pathway in animals, inhibiting the production of factors which stimulate new blood vessels growing into cancers – stopping them growing (angiogenesis). The vit-D receptor is highly expressed in many epithelial cells known to be at risk of carcinogenesis, but particularly breast, skin and prostate (Pilz). In addition to the sunlight observations mentioned above, studies have also reported a strong link between low levels of Vitamin D with a high chance of melanoma spreading. It is not a surprise then that numerous epidemiological studies have linked lower vitamin D levels with more aggressive colorectal, breast and prostate cancers which are more likely to progress faster, respond less well to treatment, relapse after cancer treatments and be fatal (Lazzeroni, Gupta, Ng, Rose, Mondul, Giovannucci).

Vitamin D supplementation:

screen-shot-2017-02-07-at-16-28-30Despite the direct causational links between sunlight, vit-D and cancer, there are some academics that believe more evidence is needed to conclude that correcting a low vitamin D with supplements directly prevents cancer and improves cancer outcomes. Indeed there are other benefits of sunlight exposure which are important for health, such as an improvement in the circadian rhythm, which in turn improves the immune system or that people working outdoor are likely to be more physically active (van der Rhee). To support their skepticism, one recent large USA appeared to report no benefit in reducing cancer risk in a randomized trial of vitamin D versus placebo. This trial however did not answer the fundamental question of whether correcting a low vit-D would be beneficial because the 2303 postmenopausal women evaluated actually had adequate to high levels of serum vitamin D at the start of the intervention (Lappe). It is therefore, logical to speculate that the trial results would be very different if researchers compared cancer levels among those who had their vitamin D levels corrected with supplements against those who continued with deficiencies. To support this speculation, a previous randomized study from Nebraska, who included 1179 women more likely to be Vit-D deficient because of their northern latitude, did report a significantly lower cancer incidence in the group who had taken Vitamin D3 (Lappe). Another multi-center involving previously untreated patient with metastatic bowel cancer looked at whether vit-D could enhance the benefits of cancer treatments. Participants were randomized to short-term high dose Vit-D or low dose Vitamin D in a double blind design. Both received standard chemotherapy treatment with mFOLFOX6 plus the biological agent bevacizumab. Although response to treatment was the same in both groups, the time it took for disease to start progressing again was significantly longer in the higher dose Vit-D group (Zgaga).

 Sources of Vitamin D.

The most important way to increase vit-D levels is to try and get regular but controlled exposure to sun although it is important not to burn and take extra precautions. Other the winter months, unless you can get a one or two holidays in the sun it would be sensible to take a vitamin D3 supplement at a dose around 1000IU (50 micrograms) per day. Otherwise the following foods contain some vitamin D:

  • Screen Shot 2017-04-22 at 00.01.24Oily fish and fish oils
  • Fresh green leafy vegetables
  • Gains and some cereals especially if fortified
  • Nuts
  • Yeast products
  • Sun dried mushrooms (their skin make vit-D just like human skin)
  • Vitamin D is commonly fortified foods

Vitamin D excess:

Vitamin D toxicity is rare and it is caused by excessive supplementation rather than sunlight. A safe upper limit of supplement dose has not been established as this depends on the underlying serum levels, dietary and sun exposure. High intake (>4000IU) for short periods of time may be needed to correct a significant deficiency but this dose is likely to create excess levels and possible toxicity if taken over several months. In general, the safe level is around 1000IU / day but up to 4000IU are likely to be safe albeit probably un-necessary. It is recommended that anyone taking over 1000IU a day should have their vitamin D and calcium levels checked for time to time.

In conclusion:

Vitamin D deficiency is common in Northern climates and this is associated with a wide number of medical conditions, an increased risk of cancer relapse and overall lower chances of survival. Further trials are required to confirm the magnitude of benefit for correcting vitamin D levels with sunlight, diet and supplements. In the mean time, the general consensus is that preventing deficiency, particularly over the winter months, is a very sensible strategy either by taking one or two holidays in the winter or regular oral supplementation. There is no evidence greater than normal vitamin D provides additional benefits and made effect calcium levels so measuring blood levels may be helpful (see micronutrient testing ).


References:

  1. Lazzeroni M et al. Vitamin D and cancer: review of RCT’s. Anticancer Agents Med Chem 2013;13(1):118.
  2. Gupta P et al. Vitamin D and prostate cancer risk. Prostate Cancer Prostatic Dis. 2009;12(3):215
  3. Vitamin D, sunlight and prostate cancer. Anti-Cancer Agent Me 2013;13(1):45-57.
  4. Chiang et al. The Anti-cancer Actions of Vitamin D. Anticancer Agents Med Chem 2013;13(1):126-39.
  5. Zgaga L et al. Vitamin D Influences Survival After Colorectal Cancer. JCO2014;32(23):2430-2439.
  6. Ng K et al. Vit-D Levels and Survival in Patients with Colorectal Cancer. JCO 2008;26(18):2984-2991.
  7. Rose et al. Vitamin D and early stage breast cancer prognosis: a meta-analysis. BJC 2001;85(10):1504.
  8. Mondul et al. Vitamin D and Prostate Cancer. Cancer Epidemiol Biomarkers Prev 2016; 25(4):665.
  9. Pilz et al. Vitamin D and cancer mortality: systematic review. Anti-Cancer Agent Me 2013;13(1):107-117.
  10. Giovannucci et al. Vitamin D and colorectal cancer. Anticancer Agents Med Chem 2013;13(1):11-19.
  11. Luscome et al. Prostate cancer associations with sunlight. Breast Cancer Res Treat 2013;141(3):331.
  12. van der Rhee et al Prevention of cancer by sunlight is more than just a vitamin D? EJC 2013; 49(6):1422.
  13. Garland et al. Meta-analysis of All-Cause Mortality According to Vit-D. A J Pub Health 2014; 104(8): e43.
  14. Wang et al. Vit-D and Chronic diseases. 2017 Aging Diseases. 2017; 8(3): 346.
  15. Lappe et al. Effect of Vit-D on cancer incidence in older women. 2007 Am Society clin Nut 2007; 85. 6,1586
  16. Lapppe et al . A RCT of vt-D versus placebo to prevent cancer. JAMA, 2017; 317 (12), 1234.