Clinical experiences with Vitamin D in a UK hospital Dr David Grimes

good afternoon to all i'm a clinical doctor and i've been fully immersed in clinical medicine since i qualified in 1966. it was about 25 years later in 1990 that to realize the importance of vitamin d excuse me in the pattern in determining the pattern of disease that i was seeing in my patients i work as a physician a gastroenterologist and the hallmark is that there's often blood on the floor one of the main skills i've had to learn over the years is the ability to leak backwards very quickly like a mongoose to get out of the firing line work in east lancashire about 30 miles north of manchester um in the based in the royal blackburn hospital nice new building which replaced the old blackmon royal infirmary which was built in 1862. looking out to the window of the hospital i often see that it's raining but not always and sometimes we can see the interesting industrial scene looking west from blackburn the industrial scenery of northwest england was portrayed so well by ls lowry and here we can see his factories we can see the factories we can see a house we can see the chimneys we can see the smoke we can see the gray sky but what larry brought to our attention more than anything was the people and we can see many of them going to the mill as the title of the the painting and the people the scene gives us a feel for socioeconomic deprivation as we would call it today the poverty of the scene the people are thin they're often stooped i'm sure they're all vitamin d deficient many of them would have had rickets many would have osteomalacia and many would have tuberculosis this set the scene for the present day when we still have problems the population of black men has a standardized mortality ratio of 143 which means that the mortality rate is 43 43 higher than the national average this is a serious problem it's a feature geographical social and ethnic factors the geography is the northwest of britain the northwest of europe the gulf stream brings warm moist air from the tropics which rises when it reaches the land meeting the cold air from the arctic and the result is is is cloud and precipitation as shown previously by oliver ethnicity a lot of the population from southeast asia and sociology we're dealing with a poor population put these three factors together and we have a serious health problem standardized mortality ratio of 143 it's all underpinned by vitamin d deficiency we can see it all on this particular slide a view looking across blackburn in the summer a few years ago we can see the grey sky we can see the absence of significant shadow the sun was not strong enough to cast a shadow and it most certainly would not be strong enough to synthesize vitamin d we can see the housing quite good housing by international standards but on the other hand not very good for vitamin d synthesis there are no gardens at one time there might have been leisure activities in the street but today the streets are taken over by the motor car there's little outdoor activity and finally we see the two girls who may be mothers or may shortly become mothers and they're almost completely covered from whatever sun there might be the three factors the geography the sociology and the ethnicity so vitamin d in blackburn i think we can summarize by saying there's not a lot of it but let's look i'm going to look at a number of patients about two and a half thousand but mainly my patients and fed in by some of the gps locally i'm not in position to undertake a random population sample although i'd very much like to do so and here's the distribution um rufus showed you a similar curve from harrow shortly before each vertical line represents one person and we can see the blood levels of vitamin d for these individuals we'll put a dotted line on 40 nanograms per mil above which i would regard as being ideal we then divide the curve at its midpoint to create a median value and we can find the median value represents the vitamin d level of about 12 nanograms per mil 50 of this group of people 2 300 had a blood level of vitamin d less than 12 nanograms per ml if we break it down in ethnicity we found out that with british names the median value represents about 18 nanograms per mill if we look at south asian names we can find is half that and the median value represents about nine nanograms per mil serious problem of vitamin d deficiency the us study i'll come back to shortly gave a median value of 23.5 twice that we found in blackburn but this was a population study in the us it was not a hospital based study with a hospital study i must emphasize these are all outpatients not in patients a lot of clinical medicine i've learned from patients over the years and i'd like to share some of that learning with you let's take for example i'll listen she presented well she came with the husband and husband had was thought to have malignancy it turned out to have polymalterumatica he's done very well i saw him analysing just yesterday her husband's blood level of vitamin d was 11 which is what i expected with the type of illness he had but there was something about allison that made me wonder whether she might have osteomalacia she had her aches and pains and indeed she did have osteomalacia and here we see it we have a normal serum calcium and we have an elevated parathyroid hormone level pth in clinical practice this is how we diagnose osteomalacia ideally we should take bone biopsies for confirmation but that's not done in normal clinical practice allison had osteomalacia and she had a blood level of vitamin d at 4.2 the cause of it was two factors first is geography living in blackman but secondly she's a strict vegetarian and it was this when she told me this i realized that austrian malaysia might be present it's not very safe being a street vegetarian in the northwest of england or indeed in scotland now this i don't know who this is but it's not alison alison does not sunbathe she's been warned to keep out of the sun by various media and she's frightened of going into the sun and this particular girl was a worker in um doville in in in brittany in normandy and she just came out to top up the vitamin d levels during a lunch break from work but alison or anybody else couldn't do this in blackburn we don't have a beach of course we're inland but people would don't lie in the sun at least not very often alison would not have kippers for her breakfast i don't very often i must say it because my wife finds them activate the house smell but occasionally in the summer i can cut them on the barbecue outside allison doesn't eat fish doesn't eat any meat she won't even take she told me yesterday after afternoon she won't even take the vitamin d that i've given her she won't or advise her to take she won't have the capsules because they come from contained gelatin she won't take vitamin d itself because she thinks she comes from an animal or fish product so she's a bit stuck she won't go in the sun and she won't take vitamin d by mouth i'll have to keep trying to persuade it to do one or the other alan on the other hand is an omnivore he'll eat anything and he presented to the clinic with reflux esophagitis which i see very frequently simple condition no problem but i noted that he had a good time a healthy tan as olive would describe it quite rightly and i asked him how that came about what sort of holidays it had he said well not much the way of holidays but i lie on a sunbed two or three times a week so i asked him if he'd mind if i checked his blood level of vitamin d out of curiosity he was very happy to do so and he's 56.8 nanograms so i wrote in with this news congratulating him on his achievement and advising him to carry on is his doing this was obviously a very good pattern of life for him mrs ahmed came to this country in 1958 from bangladesh or east pakistan as it was called them and she'd been in this country for 30 years and she presented with aches and pains all over now i've seen enough asian ladies to know that aches and pains all over equals osteomalacia does she have osteomalacia and i was quite confident she would have but no all the metabolic measures were perfectly normal and the vitamin d level was 37.8 well i couldn't believe this i thought how on earth does she have a vitamin d level of 37.8 so when she came to the clinic for follow-up i asked her about this and it appears that she eats fish from bangladesh three times a day how the fish gets from bangladesh to blackbird i have no idea but it's obviously very effective and it shows what can be done by diet but is a very enthusiastic diet eating fish three times a day anne was born in 1980 and found at birth to have spina bifida it was corrected surgically soon after birth with a very good result not perfect restoration and she was left with some disability she's got some deformity of her back walks with some difficulty but at least she can walk she was referred she went to see a gp because of my tiredness and mild diarrhea the gp did the following blood tests which i'll run through with you is because of this she was referred to the clinic these are inflammatory markers the hemoglobin should be about 13. he was suppressed at 10.9 the esr the sedimentation rate should be about 20 it was increased at 79. the crp the c-reactive protein should be less than 562. the albumin should be about 44 suppressed at 34. this syndrome with these inflammatory markers suggested she had crohn's disease and that proved to be the case it affected her terminal island the last part of the small intestine and here we see it the ct scan identifies two loops of small intestine with its characteristic thickened wall and narrow lumen characteristic of crohn's disease and we see it again on the coronal view that thickened uh segment of small intestine in the lower part of the abdomen a vitamin d level was 2.1 staggeringly low treatment was with vitamin d 20 000 units each week and after six months of vitamin d level was checked was 53.8 at that time she was feeling very well her weight had increased and the inflammatory markers had settled hemoglobin had risen esr had fallen crp had fallen and out may have risen a very satisfactory result but the point is why was um so vitamin d deficient once again a large part of the answer is geography and lives in rottendale in lancashire which is north of berry um this is a typical part of the scene the industrial revolution started here to a major extent the textile industry is close to the source of the river erwell which flows through manchester and into the manchester ship canal so the geography was one of the reasons why anne was so deficient in vitamin d but the other thing which must not forget is a disability people it's been known for many many years have a tendency for vitamin d deficiency they have less outdoor activity and al would be unlikely to take a clothes off in public due to scarring on her back from previous surgery and the deformities let's move a little further north from rossendale over the hills we're seeing the background into burnley burnley looks quite nice from a distance on a nice summer's day but on not so nice today when we get close to we can see once again a scene of social economic disadvantage and he was into this environment that abdul was born 34 years ago he presented to the clinic with abnormal liver function tests a common problem which i see and again we don't need to worry too much about the detail but we'll see that these are three liver enzymes all of which are slightly elevated we don't need to be too alarmed as with viral hepatitis for example the alt would go up to ten thousand and it was only 135 but these are characteristic abnormalities which represent some form of liver disease the hepatitis virology was negative but i noticed that his weight was 95 kilograms he was a big lad and the ultrasound scan showed features of fatty liver the reason why amble went to the doctor in the first place was because he was worried about his future most of his family members seemed to have diabetes many had corary heart disease and many had died young abdul wanted to know if his was if this was his future and what he could do about it to try and improve things he had affected the metabolic syndrome which we saw briefly earlier fatty liver diabetes coronary heart disease and early death and once again we see the family risk is underpinned by the geography the ethnicity and the social factors the environment at which abdul was born i expected his vitamin d level to be less than 10 and it was indeed 4.5 nanograms per ml his pth level was normal so i did not classify him as having osteomalacia even though he might have had osteomalacia on bone biopsy treated him with vitamin d 20 000 units per week and after six months he was feeling well of himself and his liver function tests were normal whether or not this will lead him to have a longer healthier life assuming i don't know i hope it will and i've told him he must take this this vitamin d for the rest of his life and not stop if he does stop the blood level will go down very quickly now clivero is fairly close to where i live it's a middle-class sort of place and the standardized mortality ratio is not the 145 in blackburn but it's 94. it was integrated andrew was born 35 years ago he presented to me in 1993 very ill once again with crohn's disease affecting his small intestine and we can see it here each of the yellow arrows indicates a small eroded ulcerated area in his intestine and that would have gone right through his intestine the biopsy showed characteristic features of crohn's disease nasty disease responded quite well to treatment and is he's done very well but he's still not perfect which has puzzled me i noticed over the years that he got an alkaline phosphatase level in his blood slightly elevated i thought he probably had low grade pericolangitis and inflammation of the liver which may complicate interstellar inflammation but another test the gamma gt was normal now alkaline phosphates can come from bone or from liver and when the gamma gt is normal it indicates the alkaline phosphatase is coming from bone andrew had a bone disease what might it have been well his serum calcium was normal i wonder if he might have padgett's disease but he's too young for it really i wondered about osteomalacia there was no good reason why andrew should have had osteomalacia but he did have osteomalacia normal serum calcium and elevated pth now why on earth should andrew had osteomalacia within his blood vitamin d level was 38.5 gets more curious he has what's called vitamin d resistant osteomalacia he has plenty of vitamin d but he's not working within his body and the reason is he has mutations or polymorphisms inherited from his parents of the vitamin d receptor which has been found which is found in all cells and research from oxford about 10 years ago indicates about 40 percent of patients with crohn's disease have vitamin d receptor mutations or polymorphisms it's a mutation when it's a new genetic abnormality a polymorphism when it's established within a few generations so we've looked at crohn's disease fatty liver and metabolic syndrome in individual patients let's just look at groups of patients for a moment and here we have a group of patients of mine with crohn's disease again each vertical line represents one individual patient it's not spectacularly different from the overall hospital population i thought the crohn's disease levels of vitamin d might be lower than that than they might be the higher proportion below 20. but let's remember that a lot of these people will have genetic abnormalities of vitamin d receptors fatty liver on the other hand shows a very great tendency to very low vitamin d levels virtually all have levels about 20 or below chronic liver disease and most of these will be autoimmune liver disease chronic active hepatitis primability cirrhosis and these again most of them are below 20. we've heard a little earlier on about autoimmune disease so these are autoimmune liver diseases and is there a problem with vitamin d which is leading to the disease these are people who are carriers of hepatitis c virus again most of them levels of 20 and below i thought they might be even lower because hepatitis c virus is often associated with socio-economic deprivation in the drug addiction hepatitis b virus carriers almost all who were born in eastern in the far east and we might expect therefore that they have very low levels of vitamin d perhaps that's why the virus has not been inactivated normally we develop a viral infection and our immune system inactivates the virus in these people who've got hepatitis c and b viruses the virus has not been inactivated it's still active and perhaps it's the low vitamin d levels which are responsible there have been studies of hepatitis c virus which we treat with antiviral drugs and a study from israel show that the conversion rate um to normal is much greater than vitamin d supplements are given now alcoholic disease alcoholic liver disease once again very low levels of vitamin d now how do we explain this it's worthy of further research but we might be optimistic i suppose and think that perhaps a good levels of vitamin d protect our livers from alcohol damage i hope so celiac disease i think that um the levels of vitamin d tend to be low i thought they might be lower in celiac disease chronic pancreatitis a chronic inflammatory disease effectively a pre-malignant condition once again we see that two-thirds have particularly low vitamin d levels this was reported also from manchester a couple of years ago we've heard about copd earlier chronic obstructive pulmonary disease what we used to call chronic bronchitis and what the french used to call the english disease that was just to get their own back on the english who used to call syphilis the french disease copd is a major cause of hospital admission a major cause of absence from work chronic ill health early death and general morbidity here we have low levels of vitamin d against a chronic inflammatory disease is vitamin d deficiency a major factor in the creation of copd i did not expect ulcerative colitis to be associated with vitamin d deficiency particularly and it isn't abdominal pain no pathology these are people to see we can't find out what's the matter with these people but they've got pain low levels of vitamin d very low levels indeed now this is interesting because there seems to be nothing to matter with with the abdomen of these people the problem is pain and vitamin d deficiency has been linked to pain syndromes in other situations adolescence mainly center with low weight for height very thin poor vitamin d levels again part of malnutrition perhaps and this is a particularly interesting group iron deficiency anemia and saw another four yesterday and people present with iron deficiency anemia sometimes because of obvious blood loss and sometimes with worry that they might have cancer of the stomach or colon causing occult blood loss those are sorted out and we have the ones left like this group who have iron deficiency anemia for no obvious reason and these very low vitamin d levels well is vitamin d concerned with iron metabolism there's certainly room for more research here would restoration of the vitamin d levels encourage eye metabolism i don't know the answer but it's certainly worth looking at at some stage i expected diabetes to be associated with low levels of vitamin d i don't see many people with diabetes but it confirms what we already think i thought people with cancer see quite a lot of people with cancers the esophagus stomach pancreas colon i thought that these might have lower levels of vitamin d but that turns out not to be the case again none of them has a particularly good level of vitamin d but there's no spectacular low level i see also a lot of people with chronic fatigue syndrome and this is just a subgroup of them lowest levels of vitamin d but nothing particularly outstanding but there is with chronic renal failure chronic kidney disease we see here this is another chronic inflammatory disease where vitamin d deficiency seems to be a major player again room for research this vitamin d supplement is not given in the early stages of chronic renal failure so vitamin d deficiency and the significance um is becoming fairly obvious we look at this paper from the united states this is the population study where the median level was 24.35 the standardization is on the left standardized to one is the mortality risk for people with good levels of vitamin d above 32 and as we go down we can see the three other quartiles with lower levels of vitamin d and we can see all causes of death in blue green is cardiovascular disease yellow is cancer and pink is infectious disease and all of them the risk of mortality goes up as the vitamin d level goes down arguably when an individual dies it's not of immense importance what's put on the on the death certificate as far as the individual is concerned the important thing is death and so if we take out the others we can just look at death from all causes and we can see that in those with the lowest quartile of vitamin d the mortality risk is 80 percent higher than in those with the highest vitamin d level the scale hasn't come out on here i'm afraid but the mid is one and the top line is two so it's 1.8 times 80 percent increase in mortality risk with the lowest levels of vitamin d now that's 17.8 and that is higher than the median level in the population sample in the hospital sample which i showed you earlier in blackburn if the levels of vitamin d are less than 10 i wouldn't i wouldn't know what the vitamin what the mortality risk was but it'd be very interesting to find out vitamin d supplement 20 000 units per week which we give at the hospital because we can get hold of it to crystal and this is the response to it in 172 patients the blue is before and the pink is after and the target is 40 nanograms per mil and we can see we're achieving pretty good response many are going above 40 many more above 30. it's very satisfactory these are three months after onset of treatment the response to vitamin d by injection that 300 or using the 600 000 units is rather disappointing and we very rarely hit the 40 nanogram per ml so that's three months after the vitamin d is given and it's clearly not staying around for very long so we've effectively stopped giving the intramuscular vitamin d now and we've just gone on to the oral which we can get hold of rather more easily vitamin d deficiency one other aspect of it is at what level does osteomalacia occur is there much bone disease musculoskeletal disease associated with it should should we be looking for vitamin d analogues that don't have an effect on bone or is the bone disease still important osteomalacia is the adult form of childhood rickets now this is a scattergram of vitamin d against pth and michael showed us a similar sort of thing earlier on the yellow vertical line indicates the the normal range of pth at 65. so anything to the right of the of the vertical yellow line is abnormally high and anything to the left of it is normal in all of these people the serum calcium was normal i must add by the way in all the follow-up of vitamin d um treatment which was shown the vitamin d the calcium level remained normal so all these have normal serum calcium and therefore we can say that all those to the right of the line had osteomalacia that's a lot of people with osteomalacia an awful lot of people those where the vitamin d level was above 20 we can classify as having vitamin d resistant osteomalacia some people would argue that even if the blood level of vitamin d was between 10 and 20 nanograms per mil they would also be classified as having vitamin d resistance but it's not an all or nothing thing there's a very people's vitamin d receptor efficiency varies enormously from person to person but there's a big problem with osteomalacia as you can see in the bottom left corner we can see a group of people who have very low levels of vitamin d below 20 but they have a normal pth in other words by clinical definition if not by bone biopsy they do not have osteomalacia and that is because they have very efficient vitamin d receptors now that is vitamin d receptors in bone but i'm not quite sure if we can extrapolate the vitamin d receptors in other parts of the body so the osteomalacia is seen quite commonly when the vitamin d level is less than 20 nanograms smear less than 50 nanomoles per liter the vitamin d receptor i'll just touch on again vitamin d is activated to the hormone calcium trial which enters the cells and joins with a vitamin d receptor if it's functioning to form a dimer and that dimer then enters the nucleus and in the nucleus on the genome are vitamin d responsive elements these make these switch on the genes vitamin d is actively involved in gene control but that's another lecture for now i'll leave you with the sunshine clinic which is part of our health scene until about 1960. perhaps we need the sunshine clinic to be revived thank you for your attention very nice david um one suggestion for allison since she is a strict vegetarian is to buy mushrooms take them outside in the sun it's a great way for them to get their vitamin d i shall tell her that thank you michael any other questions or comments um right at the back while you're running up there um david has written a book called vitamin d and cholesterol the importance of the sun and we have a couple of copies of people would like to come and have a look at them um the most interesting chapter in here is chapter 58 which is advice to women who would like to get pregnant and what is what david says is go away on a holiday in the sun before you want to conceive so i i commend this book thank you um julie julie griez from the army recruiting training division just a quick question you mentioned about the case where low vitamin d and normal pth and the efficiency of the vitamin d receptor would you recommend supplementation in that case well yes i think it's important to bring the vitamin d level up to the ideal range i'm afraid we can't do anything as far as i'm aware we can't do anything about people of genetically abnormal vitamin d receptors they pose it is a health problem for them at the present time we cannot investigate it it's a research tool i cannot get vitamin d receptor genetics undertaken one day i hope i will be able to so at least we can identify these people so might might those individuals be susceptible to the types of mobility that we've seen or you know we've heard about today so they've got low vitamin d but they have efficient receptors might they be susceptible to the illnesses that we've heard about well i i think that's probably true i think if people are very i don't really know if people with very efficient vitamin d receptors do have a range of illnesses or are resistant to a range of illnesses the research as far as where those researchers hasn't been done yet it's all very much a very small research project as a vitamin d receptor we don't know enough about it thank you for your your talk um i wonder if you could answer a couple of uh questions i'm from uh very close where where you're working uh uh even both we have a very high population of uh um people from the um asian southeast and asian continent who actually have very low levels of vitamin d um this this unfortunately has caused some problems with the pct because our costs have gone very high we've been told not to test and not to treat one of the problems has been that the cost of the crystal varies um and because it's a special the pharmacists can actually charge whatever they like so that's introduced some problems i'm actually uh i'm getting a visit in a couple of weeks time from the medicines management management team to emphasize this point so we have a bit of a problem um i have a couple of specific clinical questions and i wonder if you could answer them one male infertility is a problem in individuals who also happen to have very severe vitamin d deficiency and there was a mention of vitamin d deficiency in females with fertility problems i wonder whether these relevance there and whether correcting the severe deficiency might improve sperm count in males that's the first question second one is with regards to or obese patients what is it that accounts for a high incidence of vitamin d deficiency and i have a specific chap who had sleeve gastrectomy a letter came through last week that we should be supplementing him for vitamin b b12 for the rest of his life he also happened to be vitamin d deficient i wonder whether i should be uh doing the same thing for him he's improving his bmi has come down post surgery but he showed evidence of vitamin d deficiency so you're working cross-shore boolean which is part of rossendale of course now as far as the cost of decrystal 20 000 unit capsule is concerned the hospital in blackburn pays 12 pounds for 50 capsules now the it can be sold and i know rufus knows a lot about this it can be sold for 100 pounds 50 capsules it's not standardized so you need to get onto the pct about that and the other thing is you mentioned about the obesity issue well perhaps vitamin d deficiency leads to obesity i i don't know some people suggest that the relationship to obesity is one of dilution that the total body vitamin d is normal but because it's more of that body you know the vitamin d is diluted into a larger volume and therefore it goes down per mil it's less per mil i'm not quite sure michael might know more about that but it's an interesting observation the male fertility i don't know about male fertility the only thing i know is that fertility tends to be better in the spring and certainly ivf success is better in the um in the summer than in the winter this is reported from chester hospital about five years ago i don't know about male fertility i'm afraid could i pick up on something that dr beamer has just said because you are now the third doctor in this room who said something about the problem of pct looking at prescribing our vitamin d of testing and prescribing and if there's anybody else in the room who's aware of this and has some suggestions let's talk about this at the end of the day because i see this as a common theme across a number of pcts and i don't know where it's coming from and let's let's explore this together yeah in terms of obesity we had shown that if you're a bmi of greater than 30 yeah the vitamin d basically gets depot in your body fat as you only raise your blood level by about 45 so that's why they need about three to four times more vitamin d maybe from general practice i just wanted to comment as another clinician you know thanks very much for your presentation it's nice to see a breadth of medicine not just gastroenterology because i think this is one of the problems you know during my career in your career we've seen increasing specialization so we've got doctors who know more and more and more about less and less i think this is one of the issues where we are lacking champions because everybody is in their own little tiny pigeon hole i've long suspected but didn't know that uh crohn's was a vitamin d response disease is it a high response rate about a 50 response rate in my anecdotal experience this is with regard to low vitamin d levels there's been a suggestion made by perhaps well the controversial doctor dr trevor marshall who has put forward the marshall protocol for autoimmune diseases suggesting that you may have high levels of 125 hydrox hydroxyl vitamin d but suppressed levels of 25 hydroxy vitamin d you've got any comments about that basically if we're wanting to if we're interested in whether people have adequate supplies of vitamin d we need the 25 measurement the 125 tells us about the activation of vitamin d to calcium trial but i don't think it's a useful measure in standard clinical practice our our assay measures both um 25 and 125 simultaneously but of course 25 is nanograms per mill and uh 125 is picograms per ml so it's tiny tiny tiny amounts in comparison but i don't think it's a very useful clinical test yeah and i'll i'll concur that 125 levels are normal or elevated in a vitamin d deficient state because you have secondary hyperparathyroidism and regarding dr marshall i think he epitomizes the concept a little knowledge is a dangerous thing and the reason is that what he's doing he's looking only at the effect of active vitamin d and reducing immune function concluding therefore you're going to increase risk of autoimmune diseases what he doesn't appreciate is that really vitamin d plays a critical role in immunomodulation so it helps you fight infection and actually decreases your risk for autoimmune diseases

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Keywords: vitamin D, vit D, skin, cancer, sun, screen, tan, burn, lotion, block, spf, safety, UVA, UVB, UKCR, cancer research, slip, slap, slop, melanoma, multiple sclerosis, rickets, epidemic, health, medicine, UK, government, policy, department of health, news, politics, current affairs, vitamin D association, david grimes, consultant, gastroenterologist

Id: y_mCewkvoFc

Length: 42min 44sec (2564 seconds)

Published: Fri May 13 2011