So, to what extent should you be considering the vitamin D levels of your clients? What’s the evidence for the vitamin’s involvement in reducing the risk of named medical conditions? And should you be worried about potential toxicity?
Why is vitamin D important?
Most of us are well aware of the importance of vitamin D in bone health – and especially its ability to ward off the childhood bone disease rickets.
But did you know that vitamin D, (which, strictly speaking, is a steroid hormone), is involved in the expression of more than 1,000 genes (2)?This means it acts on cells in every organ of the body and has extremely farreaching effects on human health. Here are some of its key roles:
- Regulates calcium homeostasis for bone health, nerve transmission and to prevent calcium deposition in soft tissue. (Vascular calcification is a known risk factor for cardiovascular disease (3)).Vitamin D’s mechanisms here involve regulating parathyroid hormone and bone demineralisation; and controlling the extent to which calcium is absorbed from the intestine and excreted in the urine.
- Controls cell proliferation and differentiation, which may reduce the risk of cancer (4)
- Enables the immune system to be more ‘tolerant’, which may reduce the risk of auto-immune diseases (5)
- Helps to control microbes, by producing antibiotic substances, such as cathelicidin (5, 6)
- Is necessary for insulin secretion, which may be helpful in people at risk of impaired glucose tolerance and diabetes (7)
- Regulates the action of renin, which is important in controlling blood pressure (7,8).
Do your clients have optimal vitamin D levels?
According to many experts, the answer is, ‘probably not’!
Vitamin D status is assessed by measuring serum levels of 25- hydroxyvitamin D (25(OH)D3. ‘Normal’ reference ranges vary but in the UK it is approximately 40-140nmol/L. In the US the Institute of Medicine has set the threshold at 50nmol/L(9) (see note at end of article.) However, many otherwise ‘healthy’ people who get their serum levels checked are surprised to find that they are only at the bottom end of this range.
Moreover, many doctors and scientists believe that 40nmol/L is far too low for good health and that the minimum level to aim for is 75nmol/L(10,11). One argument is that the reference ranges for serum 25(OH)D are set at the level observed in people who are considered ‘normal’ only because they do not have rickets; and that the prevention of longer-latency diseases, such as cancer, requires far higher serum levels(12,13).Some experts even believe that we should be looking to reach levels as high as 100-150nmol/L if we want to reduce the risk of chronic diseases(1,13, 14).
Given that the average serum level of vitamin D is estimated to be 54nmol/L(15), it is not surprising that so many experts are concerned about a global insufficiency(1,16, 17). It has even been proposed that if the worldwide average was increased to 105nmol/L, all-cause mortality would drop by 21%, life expectancy would increase by 2 years and healthcare costs could reduce by 20%(17).
Sources of vitamin D
If Heaney and others are correct and we are indeed low in vitamin D, why might this be the case? One reason could be that it is hard to get what we need from food. In the UK, the only significant food source is oily fish. Most of our vitamin D comes from the sun. The chart below shows how it is synthesized.
But there is a problem: many people in the UK never get what they need from sunlight alone because sunlight’s ability to help us produce vitamin D is hampered by season (it only works in the summer), latitude (the UK is pretty far north), time of day (needs to be between 11am and 3pm), cloud cover (complete cloud cover reduces vitamin D synthesis by 50%), smog/pollution (most of us live in cities), skin melanin content (the darker skinned you are, the less vitamin D you’ll get from the sun) and sunscreen (SPF of 8 and above).
Even in summer, when vitamin D is most available, it is estimated that 45% of the English population have vitamin D levels of less than 40nmol/L (deficient) and that 75% fail to reach the ‘optimal’ level of 75nmol/L. Levels are worse in winter; and worse in Scotland, where people are twice as likely as the Southern English to have low serum vitamin D levels and are far more likely to suffer chronic diseases(10,11).
This situation is causing such concern to some experts that they are calling for vitamin D deficiency to be classified as a major ‘lifestyle’ risk, like smoking, alcohol, obesity and being sedentary (10, 11).
Vitamin D insufficiency and chronic disease
And indeed, vitamin D insufficiency has been implicated in many different chronic diseases, such as:
- Osteoporosis: There is a well-established link between vitamin D deficiency and osteoporosis, due to its effect on calcium metabolism. Large-scale studies in the 1990s indicated a reduction in hip fractures with calcium and vitamin D supplementation at 800 iu but not at 400 iu (7) . A more recent meta-analysis of randomized controlled trials (RCTs) found supplementing 700 to 800 iu vitamin D led to a 26% reduced risk of hip fracture versus supplementing with calcium alone or placebo (18) .
- Muscle weakness and falls: Skeletal muscle cells contain vitamin D receptors and there is reportedly a significant incidence of low serum vitamin D in people with muscle weakness, aches and pains (7) . A 2007 RCT found that nursing home residents who took 800 iu vitamin D over 5 months had a 72% reduction in the risk of falls compared with placebo (19) .
- Cancer: As early as the 1980s, it was observed that colon cancer rates were higher in areas of the US with the lowest levels of annual solar radiation (7, 17) . Since then, various different cancer cell lines have been shown to respond to vitamin D in a laboratory setting; and meta-analyses of dose-responses to vitamin D have shown a strong association between serum 25(OH)D and breast cancer risk reduction and the prevention of re-occurrence in breast cancer patients (13) . Experts predict significant risk reductions for various types of cancer, at daily intakes and serum levels higher than the current average (4, 20) . Possible mechanisms for vitamin D’s effect on cancer include reducing cell proliferation, increasing cell differentiation, increasing apoptosis of mutant cells and inhibiting angiogenesis. Thus vitamin D may affect all stages of cancer, from initiation, to progression, to metastasis (4, 7) .
- Cognitive disorders :Vitamin D receptors and vitamin D metabolic enzymes are widely distributed in the fetal and adult brain, suggesting that vitamin D is important for brain development and function (7) . Observational studies identify a link between low vitamin D and dementia, particularly Alzheimer’s Disease (AD) (21) . A recent mechanism study concluded that vitamin D may have a role in AD, when it found that a D3- enriched diet correlated with a reduction in the number of amyloid plaques and brain inflammation and an increase in nerve growth factor in the brains of transgenic mice (22) . A human study found that vitamin D added to the effect of curcumin in stimulating macrophages to clear amyloid plaques in AD patients (23) .
- Seasonal affective disorder (SAD): Broad spectrum light therapy includes wavelengths that allow the skin to produce vitamin D and this has led to the hypothesis that part of the beneficial effect from light therapy may be due to vitamin D. In a 2008 review of six mood disorder studies that measured serum vitamin D, four of them showed a significant correlation between low 25(OH)D and higher incidences of mood disorders, including SAD (24) . Some small-scale intervention studies also support the hypothesis that vitamin D may help to improve mood (25, 26) , although the overall body of evidence is still somewhat contradictory.
- Immune system problems: Epidemiologically, vitamin D deficiency is linked with chronic immune problems. Innate and adaptive immune system cells have been shown to be direct targets for vitamin D metabolites and to express enzymes to locally convert 25(OH) to its active form (27, 28) .
- Infectious immune disorders: Vitamin D has been found to stimulate pathogen elimination through a variety of mechanisms, including up-regulating the synthesis of antimicrobial proteins like defensins and cathelicidin in the mucous membranes (5, 29) . These improve resistance against bacterial infections, including periodontal disease, tuberculosis, pneumonia and sepsis. Additionally, maintaining serum 25(OH)D3 at 95nmol/L and above has been shown to reduce the risk of acute viral respiratory tract infections (30) .
- Autoimmune conditions: There is preliminary evidence that vitamin D may have the potential to help in rheumatoid arthritis, psoriasis, type 1 diabetes, chron’s, multiple sclerosis and auto-immune hypothyroidism (5, 7, 8, 31). A key mechanism is thought to be vitamin D’s ability to improve immune tolerance, by up-regulating T-regulatory cell synthesis and reducing antigen presentation by dendritic cells to T-helper cells. Both such mechanisms lead to a reduction in the proliferation of pro-inflammatory cytokines (5, 32)
- Cardiovascular disease: Observational studies indicate that individuals with lower serum 25(OH)D have a higher risk of cardiovascular disease (CVD) incidence, including heart attack, stroke and heart failure (8) Proposed mechanisms in CVD include reducing the tendency for calcium to accumulate in soft tissue, reducing LDL- and increasing HDL-cholesterol (partly through its reduction in the risk of developing type 2 diabetes), reducing the proliferation of vascular smooth muscle, improving immune tolerance, which leads to better control of inflammation, and controlling renin, which affects blood pressure (7, 8) Reduced blood pressure has been shown in hypertensive patients taking oral vitamin D and in people exposed to regular controlled UVB (8). (A 2005 observational study did not show such an effect but its inclusion of healthy people (possibly with good pre-study vitamin D levels) may have impacted on the results) (7) .
Public policy on vitamin D
In setting public policy on vitamin D, the UK and the US governments have focused primarily on bone health. They appear not to have take into account vitamin D’s many other roles, due to a lack of RCTs. (The RCT is the only study type that is generally considered to constitute true ‘evidence’. This, itself, is a cause for concern amongst advocates of integrative, person-centred healthcare.)
In the UK, there is no RNI for vitamin D, except for the elderly (400 iu or 10µg), babies (8.5µg) and young children (7µg) (33) Vitamin D testingis not usually undertaken unless there are exceptional circumstances, such as having a bone disease, being pregnant or breastfeeding, or being covered up or housebound for long periods. Moreover, The NHS advises caution with regard to sun exposure, (due to the risk of skin cancer), and vitamin D supplementation, (due to potential toxicity) (34) .
This type of guidance has been heavily criticized by doctors and scientists in the US and the UK (11, 17, 35) . They are concerned that it could lead GPs and patients to assume that, unless they fall into one of the special categories listed above, there is no need to be concerned about vitamin D status. How many of your clients, for example, are aware of the crucial importance of getting an adequate amount on a regular basis?
The concern around toxicity is due to the potential for hypercalcaemia at excessive vitamin D levels. However, recent studies have indicated that we would need to supplement extraordinarily high doses in order to reach the ‘toxic’ threshold. For example, a 2007 review of 15 human intervention trials showed that up to 10,000 iu/day is safe (36) and a 5-year 2011 study indicated that even a dose of 40,000 iu/day is unlikely to be toxic (37). The UK’s Expert Group on Vitamins and Minerals acknowledges that supplementing as much as 4000iu/day is unlikely to have any effect on blood calcium levels (33, 38).
In the US, public health messages stress that serum levels of more tan 125nmol/L can cause ‘adverse effects’ (9). However, critics claim that this cautious stance is based on the results of a study that used a single, annual mega-dose of 500,000 iu, which would have led to a sharp but transient rise in serum levels, followed, two months later, by ten months of pre-dosing (i.e. inadequate) levels (39, 40) . This is because the half-life of vitamin D is only 60 days. By implication, even if your clients are able to get enough vitamin D from sun exposure in the summer months, they are likely to be deficient in the winter unless they can obtain it from other sources.
Vitamin D Supplementation
So, should we supplement, and, if so, how much? Vitamin D supplements come in two forms: D2 (ergocalciferol) and D3 (cholecalciferol). D3 is the natural form and is thus considered to be more bioavailable than D2. Most multi-vitamin supplements contain low enough levels (typically 200 to 400 iu) to take daily without issue but if you are going to prescribe therapeutic doses, the most sensible course of action would be to test serum levels first, preferably via the client’s GP.
If serum levels are found to be lower than optimal (75nmols/L as a base; 100-1 50nmols/L according to some experts), encourage more intake from food and sensible sun exposure. This means exposing skin daily, in the middle of the day, without sunscreen. Start with 2 to 3 minutes only, and build up gradually to a maximum of 30 minutes, taking care not to burn. Seven major UK health charities, including Cancer Research UK and Diabetes UK, have now developed a new joint position statement on vitamin D and sun exposure: ‘Enjoying the sun safely, while taking care not to burn, can help to provide the benefits of vitamin D without unduly raising the risk of skin cancer.’
If necessary, consider vitamin D supplementation at a level according to baseline serum levels, the skin type and the client’s diet and lifestyle going forward. The rate at which serum levels rise tends to vary between individuals. A re-test in 3 to 6 months will enable you to monitor and control the dose to the best effect.
Vitamin D has long been known as an important nutrient for skeletal health. But there is now emerging evidence that links vitamin D inadequacy with the development of many other long-term, chronic illnesses. There is still significant disagreement on the extent of vitamin D deficiency and the extent to which increasing levels may reduce the burden of chronic disease. We hope that this information on vitamin D has helped to explain some of the key issues surrounding vitamin D in human health and that it will help you in educating your clients, enabling them to make informed choices with regard to diet, lifestyle and supplementation.
Note: Some UK labs have now moved to µg/L, with values approx 25% of nmol/L values. To convert µg to nmol, multiply µg by 2.5
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