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Vitamin D and Cancer

by Angus Dalgleish(more info)

listed in cancer, originally published in issue 255 - June 2019


Vitamin D has long since been recognised as crucially important to health and its first association was with Ricketts, in that supplementation with Vitamin D in children with Ricketts could reverse the disease and prevent further recurrence.  Indeed, this association is so well known that even today many doctors think this is the sole association.  Over the years it has become very clear that Vitamin D deficiency is associated with many of the health problems associated with Western lifestyle, including heart attacks, strokes, diabetes, multiple sclerosis, etc., as well as cancer.

Vitamin D  

The best review of all these associations and their improvement with Vitamin D supplementation is a book called Vitamin D and Cholesterol: The Importance of the Sun by Dr David Grimes, published by Tennyson Publishing in 2009.  Dr Grimes is a Gastroenterologist working in Lancaster who was  conducting clinics in Blackpool and a town several miles inland, where he couldn’t help but notice that patients in Blackpool did very much better than their inland counterparts, whatever condition he was treating.  This led to his discovery that Vitamin D was the ‘Occam’s razer’, i.e. the one thing that could explain everything, as patients in Blackpool were more likely to have healthy levels of Vitamin D than the inland region very low levels of Vitamin D as it was notorious for always raining and having very few hours of sunshine.

One of the unexpected findings uncovered in this book is the fact that hypertension is often associated with low Vitamin D levels and this can be corrected by supplementation. 

It has been known for several years that Vitamin D is very important for immune function, especially T-cell killing and this includes tumours, as well as having an anti-proliferative effect on tumour cell lines.  However, it was the unexpected finding that patients with thick melanomas were more likely to have lower levels of Vitamin D than patients with thin melanomas, first reported by Professor Newton-Bishop’s group in Leeds.


Vitamin D3 - Cholecalciferol-3d

There is now much evidence that a low Vitamin D3 level is indicative of a poor outcome in many cancer types, including breast, prostate, colorectal and even pancreatic cancer.  The most likely explanation for this global impact is that it is important in several aspects of controlling cancer, including having a direct anti-proliferative effect, as well as being vital for an effective immune response.  It is required so dendritic cells can efficiently present antigen, as well as modulating this activity to prevent autoimmunity.  Primed killer cells are not efficient in the absence of Vitamin D3, so it is important therefore both the input and output of the immune response against cancer cells.  Its overall effect on the immune system has been known for decades, as prior to the effective treatment of tuberculosis, the only hope of a cure was to go to south of France or Italy and spend six months in the sun.  The fact that this was the only effective treatment likely to have a positive outcome (but not guaranteed!) suggests that improving Vitamin D status in cancer patients could also be therapeutic.

Critics have suggested that the association does not necessarily mean that correcting it will have any benefit and we need randomized studies of Vitamin D3 supplementation to prove this.  However, given the overwhelming benefit seen with correcting low levels of Vitamin D3 with supplementation, either synthetic analogues or cod liver oil, with the improvement in rickets and tuberculosis, etc., many would argue that this is unnecessary and anyone with a low level should have it corrected, especially as the beneficial effects have been shown to apply to so many other conditions.  There are some papers suggesting that supplementation is not helpful, but in retrospect this only goes to highlight the importance of having the right Vitamin D3.  Cholecalciferol or Vitamin D3 is the only one that is active.  Previous studies have included Vitamin D2 which has no therapeutic effect when given orally and the doses given would be regarded to correct significant deficiency.

Professor Angus Dalgleish

Professor Angus Dalgleish – The Institute for Cancer Vaccines and Immunotherapy

In a recent study at St. George’s Hospital in south west London it was found that 85% of all patients tested sequentially in a melanoma clinic had Vitamin D3 levels below the lower limit of normal.  A third of these were extremely low and several of those who were in the normal range were taking Vitamin D supplements, sometimes in the form of cod liver oil!  A major question has to be asked why such an important agent is so low across the population.  It is clearly associated with a lack of sunshine and the levels are much worse in winter than at the height of summer.  Moreover, those areas with a large Asian or African population are even worse, as melanin pigmentation has evolved to protect from sun rays and therefore in a non-tropical environment it greatly inhibits the sunshine synthesis in the skin.  There are also many other reasons, including the bizarre and complex absorption and availability of the active ingredient of the Vitamin D pathway.  Following absorption it requires processing in the liver and kidney, as well as in the skin, with sunshine, and it is estimated that there are over three hundred genes which are involved and if any of these have a slight mutation the efficiency is reduced.

Another feature relevant to cancer, which has been researched in depth, is the polymorphism of the Vitamin D receptors of different cells.  From a practical point of view, it is evident from retrospective research that patients who have low Vitamin D3 levels respond poorly to immunotherapy, whether it be cancer vaccination or the newer agents.  Patients with low Vitamin D who are supplemented and brought into the higher level clearly do much better and there are many anecdotes of patients with progressive recurring disease that go into remission upon correcting low Vitamin D levels and adding in anti-inflammatory agents, such as Aspirin and through dietary modification. 

Recent detailed studies looking at the inflammatory and immune status of patients receiving immunotherapies of various descriptions have shown that those who have an inflammatory state respond poorly and this is likely to be associated with lower Vitamin D levels.  In this regard it is important to note that Vitamin D is a powerful anti-inflammatory agent, as well as enhancing the immune response against various antigens and this is probably why it is so important in multiple sclerosis.

There are many reasons why its effect on the immune system could have such a marked impact on response to immunotherapy in patients, but it is much less appreciated that patients who respond poorly to chemotherapy also have low Vitamin D levels and this has been particularly shown for patients receiving chemotherapy for pancreatic cancer, whereas the only patients that respond well are the only ones with normal Vitamin D levels.  This is thought to be due to its very important effect on transcription factors in the microenvironment around the tumour, as well as on the immune response. 

Overall, the body of evidence on the importance of Vitamin D in preventing and delaying cancer, across all different types, is overwhelming and it is surprising that a greater initiative has not been made of this with regards to cancer prevention programmes and improving cancer outcomes.  Vitamin D3 supplementation is incredibly cheap, especially compared to the cost of even normal, non-expensive medicine, such as those used to treat hypertension and diabetes, both conditions that would improve with supplementation and reduce the need to take drugs that currently cost the NHS billions.  It is also likely that the impact on cancer management would be even greater now that most tumours can be treated with new drugs that cost between £5,000 and £10,000 a month.

From a cancer doctor’s point of view, whether a surgeon, medical oncologist or radiotherapist, the easiest and quickest part of this plan is to measure the Vitamin D3 level and correct it before doing anything else.


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About Angus Dalgleish

Professor Angus Dalgleish is Professor of Oncology at St George’s University of London and Principal of the Institute for Cancer Vaccines and Immunotherapy. He may be contacted on Tel: 020 8725 0809;  St George’s University London  and The Institute for Cancer Vaccines and Immunotherapy

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