OVERVIEW
· Bone health is just the start of the vitamin D story. We unravel this nutrient’s profound and far-reaching consequences for our health.
· Studies show that vitamin D influences our risk of virtually every modern-day health problem, including cancer, heart disease, diabetes and more.
· The breaking story is that the epidemic of vitamin D deficiency is leaving a vast burden of economic and health consequences trailing in its wake.
· Could vitamin D be one of the greatest medical breakthroughs of our times?
Nearly all the early research on vitamin D was dedicated to establishing its importance for bone health. There’s a whole other side to this story, though, which has recently burst to the fore, with an explosion of research showing that vitamin D is crucial to many aspects of our health. We’re not talking about a few minor health issues here, but some of THE most pressing health issues of our times. As a result, there’s an almighty buzz about vitamin D.
Here’s why. Low vitamin D levels are now associated with the risk of different cancers, diabetes, cardiovascular disease, multiple sclerosis, rheumatoid arthritis, osteoarthritis, pre-eclampsia, caesarean delivery, depression, Alzheimer’s disease, infectious diseases and neurocognitive dysfunction. That’s quite some list! Let’s forget all the high-tech medical treatments for a minute: is it possible that a deficiency of a simple vitamin could be at the heart of our modern-day health problems?
It’s a pretty mind-blowing thought, and one that’s even captured the attention of the bureaucrats. During a parliamentary questions session of the EU Commission in 2010, it was announced that the ‘economic burden attributed to insufficient vitamin D consumption is estimated at 187,000 million euros (260 billion dollars) per year’1. That’s serious money. Disease, be gone. Financial crisis, be gone. Welcome to a vitamin D-driven utopia!
With all this going on, it’s not hard to see why vitamin D is often described as the ‘vitamin of the decade’. However, is this all too good to be true? After all, we all know how easy it is to get swept away with the fervour of something exciting, and before we know it we’ve lost all sense of perspective (just look at the whole antioxidants fiasco). So, without further ado, we’re going to give you the real story.
Bring me sunshine
It all started with some intriguing observations during the 1930s, when a study of the highly sun-exposed US Navy found that their death rate from non-skin cancer was 60% less than in the civilian population2. Since then, it’s been observed that simply living at higher latitudes (which means less sun exposure) is linked with increased risk of cancers such as colon, breast, prostate and several others3. Indeed, if you are diagnosed with breast, colon, prostate cancer or Hodgkin’s lymphoma in summer or autumn (the times of year when vitamin D levels are at their highest), you have a much improved three-year survival rate than if you were diagnosed in winter or spring4,5.
We can draw the very same comparisons for cardiovascular disease too – a greater incidence occurs in populations living at higher latitudes, with greater increases found during the winter months6. And the list just grows from there. When it comes to a host of autoimmune diseases, such as Crohn’s disease, type 1 diabetes, rheumatoid arthritis and multiple sclerosis, a similar trend between greater sun exposure and a reduced risk of these diseases has been documented7,8,9,10. With the discovery of vitamin D receptors on almost all tissues in the body, the sheer breadth and range of diseases that vitamin D deficiency has now been implicated in is simply stunning.
We could go on and on, so we decided to pin our focus on the big three – cancer, heart disease and diabetes.
Collectively, cardiovascular disease (including stroke), cancer and diabetes account for 1.4 million of the 2.4 million deaths in the USA each year11. Figures from 2004 show that these conditions were costing the economy an estimated $700 billion annually12, and this has only increased since.
‘D’ and the big ‘C’
When it comes to investigating the influence of sunlight exposure, the USA offers a unique case study. It’s a country where UV exposure can vary considerably by region, even at the same latitudes. Of interest is the observation that there is a distinct east–west difference in cancer mortality rates across the USA, even though diets are broadly similar13. West of the Rocky Mountains, land elevations are higher and the stratospheric ozone layer is thinner, which allows greater UVB penetration and enhanced ability to synthesize vitamin D13,14. Could something as simple as vitamin-D boosting sunshine explain the geographical variation in cancer mortality rates across the US? Let’s see if we can get some answers.
A large US ecological study carried out between 1950 and 1969 and 1970 and 1994 found that those people living in areas with the greatest UVB exposure had significantly reduced levels of 15 different cancers14. This was true even after accounting for potential confounders, such as smoking, ethnicity, alcohol consumption, affluence and urban residence. So strong was the observed effect of higher levels of UVB exposure that the authors calculated it would equate to saving up to 60,000 lives each year – a staggering 10% of the US death toll due to cancer. (It’s an interesting aside that in the 1980s the strength of this association decreased, corresponding with the introduction of anti-skin cancer campaigns to limit sun exposure, and the recommended use of sun block.)
As exciting as all this sounds, we should curb the enthusiasm just a bit by saying that these are all ecological studies, from which we shouldn’t be jumping to any definitive conclusions. It begs the important question: how plausible is all this information? Could vitamin D really stop something as deadly as cancer in its tracks? If we look at what vitamin D actually does in the tissues of the body, then we begin to see how this could work.
We can think of vitamin D as being on sentry duty at checkpoints in a cell. If the cell is attacked (e.g. causing DNA damage), or if there’s any reason that it’s not functioning properly, vitamin D helps sound the alarm, as well as enabling cell defence mechanisms to kick in. Unwanted cell growth is halted and damaged cells are destroyed. Without this early guard duty, corrupted cells are allowed to grow and replicate in an uncontrolled manner. By the time our body’s defences are alerted and mobilized, it’s too late. They are quickly overwhelmed and cancer gains the upper hand.
Amazingly, there are more than 1,000 human genes with vitamin D response elements15, with many involved in making important proteins that help to regulate essential functions such as cell proliferation, differentiation and apoptosis, all of which need to be tightly controlled to stave off cancer.
Every two minutes, someone in the UK is diagnosed with cancer16.
So far, evidence for a cancer-protective effect of vitamin D looks strongest for colorectal cancer and breast cancer. The National Health and Nutrition Examination Survey in the USA found that those with vitamin D levels greater than 32ng/ml had 72% fewer deaths from colorectal cancer compared to those with levels less than 20ng/ml17. This impressive effect was still seen even after accounting for BMI (body mass index) and physical activity levels – two factors which not only affect vitamin D levels, but also directly affect the risk of colorectal cancer. Rather than just being a one-off, these exciting findings have been borne out by other observational studies. In a meta-analysis of studies, which prospectively examined vitamin D levels in relation to colorectal cancer, having levels of 33ng/ml or more was associated with a 50% lower incidence of colorectal cancer compared with having levels of 12ng/ml or less18.
When it comes to breast cancer, a meta-analysis of seven trials examining circulating vitamin D levels found that those with the highest levels had a 45% reduced occurrence of breast cancer compared to those with the lowest levels19. In a second meta-analysis of nine observational trials, raising vitamin D levels by 20ng/ml was associated with a 27% reduction in breast cancer occurrence20.
In 2007, there were 345,636 cases of breast and colorectal cancer in the USA, with 93,817 people dying that year from these two diseases21.
As we know, the evidence from observational studies is just a teaser, highly suggestive but never definitive. True evidence of cause and effect can only come from rigorously performed RCTs. Unfortunately, when it comes to vitamin D these are still very thin on the ground. In fact, there is not a single large-scale RCT of vitamin D where cancer has been pre-specified as the primary outcome of the study22. So, where RCTs do exist, we have to ask how relevant are they?
We’ll take the Women’s Health Initiative trial as our example. This found no effects of vitamin D after seven years on risk of colorectal cancer or breast cancer23,24. But before you think this blows the whole vitamin D story out of the water, you have to realize that this study was designed in the early 1990s, before the big surge of interest in vitamin D as a cancer protective nutrient had gathered pace. The dosage used was a mere 400IU per day (and if you take the poor adherence of the participants into account, it would be much lower). This is virtually a meaningless amount and far below the higher levels that have been observed to have a protective effect against cancer.
The second RCT used a more meaningful vitamin D dose of 1,100IU per day. This raised the participant’s vitamin D levels from an already very respectable 28ng/ml to an even higher level of 38ng/ml. This 10ng/ml rise in vitamin D levels was associated with a 35% reduction in total cancer risk25. Unfortunately, what seemed an extremely promising finding was tempered by considerable criticism of the study’s methodology26,27,28 including the fact that there were unexpectedly high rates of cancer in the placebo group, which may have artificially skewed the results in favour of vitamin D28,29.
So, we still need to await the results from more rigorous RCTs to truly prove the cancer link. But all in all, things look quite promising, and if there really is no smoke without fire, it looks like vitamin D is essential to ensure incineration of those malignant cells.
Cardiovascular ‘D’-sease
Look up any list of cardiovascular disease risk factors and broadly speaking, they’re always the same. You’ll see the usual suspects, such as obesity, smoking, lack of exercise, elevated cholesterol, triglycerides and homocysteine, eating a lot of salt and so on. We’re pretty sure that you won’t see vitamin D listed anywhere. Yet evidence is mounting to demonstrate the necessity of sufficient vitamin D levels for heart health too.
While deaths from heart disease are falling, it still remains the Western world’s biggest killer. More than 616,000 people die from heart disease in the USA each year30. Heart disease carries with it an annual economic cost of over $445 billion in the USA alone31.
Results from the Health Professionals Follow-up Study support this idea. They showed that men deficient in vitamin D (<15ng/ml) had more than double the risk of a heart attack compared with men with higher vitamin D levels (>30ng/ml)6. In 1,739 participants from the Framingham Offspring Study, those with a vitamin D level less than 15ng/ml had 62% more cardiovascular events compared to those with a vitamin D level above 15ng/ml32. Another study indicated that the risk of being diagnosed with hypertension over a four-year period was more than three times greater in those with vitamin D levels below 15ng/ml, compared with those who had a level of 30ng/ml or above33. Having low levels of vitamin D has additionally been linked to increased risk of fatal strokes34, heart failure and sudden cardiac death35.
Vitamin D has quite some litany of benefits, but does it all stack up? How does it work its magic? Are these observations biologically plausible?
It appears so, as vitamin D works in a number of ways to protect the cardiovascular system – affecting the proliferation of smooth muscle cells, reducing inflammation, helping to control calcification of blood vessels, improving endothelial function, and even reducing blood pressure, all things that can affect the risk of heart disease6,36
But once again, show us the well-designed RCTs? There’s the Women’s Health Initiative study again, but as with cancer, it’s pretty useless and the lack of benefit observed was hardly surprising given the small dose of vitamin D and the low adherence of the participants actually taking the supplements. There have been a couple of studies which tentatively suggest that higher doses of vitamin D supplements (820IU37 and 1,000IU38 daily) reduce cardiovascular disease. But the results were not strong enough, nor the trials well enough designed to draw any firm conclusions, underlining the need for better studies to be conducted.
‘D’ for diabetes
As if protection against cancer and heart disease wasn’t enough, evidence is growing that vitamin D may also prevent one of the other major diseases of our times, diabetes. It makes sense too, when you consider that vitamin D appears to be involved in the functioning of beta cells (the cells that make and release insulin), insulin sensitivity and levels of inflammation in the body, all of which influence how well we can handle glucose and, ultimately, the risk of type 2 diabetes39.
Worldwide, the number of people with diabetes is expected to rise from 171 million in 2000 to a staggering 366 million by 203040.
Type 2 diabetes has serious long-term health consequences (it affects the kidneys, eyesight, gums, heart and nervous system), and simple ways of preventing it, such as getting enough vitamin D, are desperately needed.
In the USA, in 2006 alone, 65,700 diabetics had to have a lower limb amputated41.
These fancy ‘mechanisms’ are all well and good, but what happens in the real world? A review of observational studies found that intakes of vitamin D greater than 500IU daily decreased type 2 diabetes risk by 13%, compared with vitamin D intakes of less than 200IU per day42. According to vitamin D status, those with the highest vitamin D levels (>25ng/ml) had a 43% lower risk of getting type 2 diabetes compared to those with the lowest levels (<14ng/ml)42. This is similar to another review, which found that having higher vitamin D levels (25–38ng/ ml) was associated with a 64% reduction in the prevalence of type 2 diabetes, compared with those who had lower levels (10–23ng/ml)43, although this link was only clearly demonstrated once data on non-Hispanic blacks was excluded from the analysis.
Concrete evidence from RCTs is required to establish proof. In just such a trial, diabetics were given vitamin D-fortified yoghurts providing 1,000IU per day for 12 weeks44. The baseline vitamin D levels at the start of the study were, on average, 18ng/ml, with 70% having levels less than 20ng/ml, and rose to an average of 30ng/ml with the intervention. The increase in vitamin D status corresponded to a significantly lower weight (2kg loss) and waist size (2.5cm / 1in / 2.5% reduction) compared to the placebo group, as well as improvements in measures of blood sugar control.
Vitamin D’s anti-diabetes credentials are not just limited to type 2 diabetes, but extend to type 1 diabetes too. This is a very different condition, in which the body’s immune system attacks and destroys the insulin-producing beta cells of the pancreas. In contrast to type 2 diabetes, which typically affects older people, type 1 diabetes is usually diagnosed in childhood. A low number of sunshine hours has been shown to correlate with the incidence of type 1 diabetes45, as too has seasonal variations in diagnosis (higher in late autumn and winter, lower in summer)8,46. Vitamin D levels have also been found to be lower in people at the time of diagnosis of type 1 diabetes compared with controls47.
Although type 1 and type 2 diabetes are very different diseases, vitamin D appears to help prevent both.
Vitamin D intake during pregnancy, lactation and infancy appears to reduce the risk of going on to develop type 1 diabetes. The immunomodulatory effects of vitamin D are well documented and it is by these actions that the risk of type 1 diabetes is believed to be reduced. A recent meta-analysis concluded that supplementation with vitamin D in infancy was associated with a 29% reduced risk of type 1 diabetes48. In Finnish infants aged one year, the reduction in the incidence of type 1 diabetes in those who regularly received very high dose vitamin D supplementation was 88%49. Tellingly, in those infants suspected of having rickets, suggesting extreme vitamin D deficiency, there was a threefold increased risk of developing diabetes.
THE PARTING SHOT
It’s now crystal clear that vitamin D plays a far more complex role in the body than simply being important for healthy bones. With the vitamin D receptor expressed in most tissues of the body, it’s hardly surprising that a lack of vitamin D has multiple adverse health consequences. It is linked not just to cancer, heart disease and diabetes, but also multiple sclerosis, rheumatoid arthritis, dementia, pre-eclampsia, and even infectious diseases such as influenza50 It therefore comes as no surprise that taking vitamin D supplements is associated with a lower mortality rate51.
Vitamin D is undoubtedly the ‘in’ supplement, but with so much of the evidence coming from observational and lab research, it remains a cliffhanger that leaves us dangling until the final chapter is written. We need properly conducted RCTs, and the conclusion to the vitamin D story looks likely to come from the VITAL study. This is a large RCT investigating the effects of vitamin D supplementation at 2,000IU per day in the prevention of cancer, heart disease and stroke in US adults over 50, as well as exploring whether there are any effects on the other health outcomes that we’ve discussed in this chapter. Unfortunately, with the trial just getting started, it will be at least five to six years before we start to get some real answers. In the meantime, we can only side with the inescapable conclusion that having a low vitamin D level won’t do you or your health any favours.
With the stakes this high, in the next chapter we’ll show you how to stay ahead of the curve when it comes to your health, with our guide to achieving optimal vitamin D levels.
SUMMARY AND RECOMMENDATIONS
· Low levels of vitamin D are widespread and likely to increase the risk of many chronic and life-threatening health problems.
· Evidence suggests that rates of cancer, heart disease, diabetes and autoimmune disease could be lowered significantly if we have adequate vitamin D levels.
· The good news is that the levels needed to realize this benefit are the same as for bone health, which is above a minimum of 20ng/ml, and nearer to 30ng/ml.
· We still need concrete evidence from well-conducted randomized controlled intervention trials.
· Until more results come to light, the weight of evidence to date supports the use of an appropriate regime to safely raise your vitamin D levels. This is laid out for you in the next chapter.