Vitamin D Deficiency

Written by Dr. Steve Chaney on . Posted in Health Current Events, Healthy Living, Supplements and Health, Vitamins and Health

What Is The Real Vitamin D Story?

Author: Dr. Stephen Chaney

 

Vitamin DIf you are like most people, you probably don’t know what to believe about vitamin D deficiency. Some experts tout vitamin D as a miracle nutrient that will help you lead a longer, healthier life. They leave you with the impression that everyone should be supplementing with vitamin D.

Other experts tell you that the supposed benefits of vitamin D are all hype. They tell you not to waste your money on vitamin D supplements.

When you pull back the curtain and look at the clinical studies behind the headlines, a pattern begins to emerge.

Most of the studies that support a role for vitamin D in preventing heart disease, preventing cancer and extending life have been population studies. They have compared populations with low vitamin D intake with populations with adequate vitamin D intake. While population studies are good for suggesting associations, they have their limitations:

  • Population studies are good at suggesting associations, but they do not prove cause and effect.
  • With population studies it is also very difficult to eliminate what scientists call “confounding variables”. Let me give you an example. Suppose someone had low 25-hydroxyvitamin D levels in their blood because they sat around all day watching TV and never got out in the sun. If they got sick you wouldn’t really know whether it was due to low 25-hydroxyvitamin D levels or due to inactivity. In this case, inactivity would be a confounding variable.

On the other hand, most of the studies that fail to find any benefit of vitamin D are double blind, placebo-controlled intervention studies in which one group was given supplemental vitamin D and the other group was given a placebo. While these studies are considered the most reliable clinical studies, they have their limitations as well.

  • In the case of vitamin D many of these studies were done with a cross section of the population in which most of the participants already had adequate blood levels of 25-hydroxyvitamin D at the start of the study. Those studies are incapable of telling us whether correcting a vitamin D deficiency would have been beneficial.
  • Even when the intervention studies focus on participants with low vitamin D status at the start of the trial they have another significant limitation. They are all short term studies. Typically, the best of these studies last no more than a couple of years. Longer term studies are far too expensive. In contrast, diseases such as heart disease and cancer take decades to develop. A one or two year intervention with vitamin D simply may not be sufficient to correct the damage caused by decades of vitamin D deficiency

This is the current dilemma that is creating all of the confusion in the vitamin D story. For the most part, population studies and intervention studies are coming to very different conclusions. And both kinds of studies have inherent limitations that are difficult to overcome.

Fortunately, a new kind of clinical study has been developed in recent years that overcomes the limitations of both population studies and intervention studies.

A New Kind of Clinical Study

Bad GenesThe new approach is something called mendelian randomization. I apologize for the scientific jargon, but let me explain. In this case you are separating your population based on genetic variation rather than on the basis of biochemical or behavioral differences.

 

For example, in the clinical study I will describe in a minute the population was separated into groups based on genetic variations in the DHCR7 and CYP2R1 genes. The first gene is involved in the biosynthesis of cholesterol, which is a precursor of vitamin D, and the second gene converts vitamin D to 25-hydroxyvitamin D. Both genes affect blood levels of 25-hydroxyvitamin D.

This kind of study has several unique strengths:

  • Genetic variations are unaffected by confounding variables such as sun exposure, obesity, smoking, inactivity, and poor diet. If the study population is large enough, those confounding variables will be equally distributed among groups that are selected solely on the basis of genetic variations.
  • These studies are long term by definition. If someone has a genetic variant that lowers their 25-hydroxyvitamin D level, it will do so for their entire lifetime. They can increase their vitamin D status by sun exposure, for example, but their blood levels of 25 hydroxyvitamin D will always be less than someone with equal sun exposure who does not have that genetic variant.
  • Because these studies reflect lifelong exposure to 25-hydroxyvitamin D they are ideally suited for measuring the effect of vitamin D status on mortality and diseases that take decades to develop.

Do Vitamin D Genes Affect Mortality?

This study (S. Afzal et al, The British Medical Journal, 2014;p 349:g6330 doi: 10.1136/bmj.g6330) combined the data from three clinical studies conducted in Copenhagen between 1976 and 2013. The age of the participants ranged from 20 to 100 years and the follow-up was 6-19 years. 95,766 participants in these studies were genotyped for variants in the DHCR7 and CYP2R1 genes which were known to affect 25-hydroxyvitamin D levels. 35,334 of those participants also had blood 25-hydroxyvitamin D levels determined. By the end of the study 10,349 of the participants had died.

  • The individual genetic variants included in this study caused a relatively small (1.9 nmol/L) decrease in blood levels of 25-hydroxyvitamin D. However, because this was a very large study and the participants with those genetic variants were exposed to lower 25-hydroxyvitamin D levels for their entire lifespan, the decreased 25-vitamin D levels were associated with significant increases in all cause mortality and cancer mortality, but not with increased cardiovascular mortality.
  • When they extrapolated to a genetically caused 20 nmol/L decrease in 25-hydroxyvitamin D, the decrease in 25-hdroxyvitamin D was associated with a 30% increase in all cause mortality and a 30% increase in cancer mortality.

What Kind Of Studies Are Needed Next?

The authors noted that this is the first study of its kind, so it obviously needs to be confirmed by other large mendelian randomization studies that test the link between vitamin D status and mortality.

Ideally, it should also be verified by double blind, placebo controlled intervention studies, but that may not be possible. If one really wanted to verify this study, the intervention study should start with a population group with 25-hydroxyvitamin D levels at least 20 nmol/L below what is considered adequate and provide them with enough supplemental vitamin D to increase their 25-hydroxyvitamin D to the adequate range. That is difficult, but doable.

However, the intervention study would also need to be long enough (decades perhaps) to prevent cancer from developing. That kind of study will probably never be done.

 

The Bottom Line

  • The relationship between vitamin D status and mortality has been investigated with a new type of clinical study based on what is called mendelian randomization. Population groups were segregated based on genetic variations in two genes that affect blood 25-hydroxyvitamin D levels (a measure of vitamin D status).
  • This study concluded that a genetically determined decrease of 20 nmol/L in blood 25-hydroxyvitamin D was associated with a 30% increase in all cause mortality and a 30% increase in cancer mortality, but had no significant effect on cardiovascular mortality.
  • This kind of study is particularly strong because it measures the affect of lifelong exposure to 25-hydroxyvitamin D. This is important when assessing the effect of vitamin D status on mortality and diseases such as cancer that take decades to develop. In contrast, the double blind, placebo controlled intervention studies that are consider the “Gold Standard” for clinical studies may be too short term to adequately assess the effect of vitamin D status on cancer or all cause mortality.
  • This study supports the benefit of maintaining optimal vitamin D status, but it is the first clinical study of its kind and needs to be confirmed by other studies.
  • In the meantime, there is no harm to in maintaining your blood levels of 25-hydroxyvitamin D in the optimal range through diet, sun exposure and supplementation. This study suggests it just may help you live a longer, healthier life.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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Comments (1)

  • Doreen Harrison

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    Love your newsletter, Health Tips From The \professor. I am on you list and want to continue to be so. Thank you for the work you do. I would like to include some of your work in my monthly newsletters if that is OK with you,

    greetings from Canada

    Doreen

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Latest Article

Should We Use Supplements For Cardiovascular Health?

Posted July 10, 2018 by Dr. Steve Chaney

Are You Just Wasting Your Money On Supplements?

Author: Dr. Stephen Chaney

 

supplements for cardiovascular health wast moneyYou’ve seen the headlines. “Recent Study Finds Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.”  You are being told that supplements are of no benefit to you. They are a waste of money. You should follow a healthy diet instead. Is all of this true?

If I were like most bloggers, I would give you a simple yes or no answer that would be only partially correct. Instead, I am going to put the study behind these headlines into perspective. I am going to give you a deeper understanding of supplementation, so you can make better choices for your health.

 Should we use supplements for cardiovascular health?

In today’s article I will give you a brief overview of the subject. Here are the topics I will cover today:

  • Is this fake news?
  • Did the study ask the right questions?
  • Is this a question of “Garbage In – Garbage Out?
  • Reducing Heart Disease Risk. What you need to know.

All these topics are covered in much more detail (with references) in my book “Slaying The Supplement Myths”, which will be published this fall.

 

How Was This Study Done?

supplements for cardiovascular healthThis study (D.J.A. Jenkins et al, Journal of the American College Of Cardiology, 71: 2540-2584, 2018 ) was a meta-analysis. Simply put, that means the authors combined the results of many previous studies into a single database to increase the statistical power of their conclusions. This study included 127 randomized control trials published between 2012 and December 2017. These were all studies that included supplementation and looked at cardiovascular end points, cancer end points or overall mortality.

Before looking at the results, it is instructive to look at the strengths and weaknesses of the study. Rather than giving you my interpretation, let me summarize what the authors said about strengths and weaknesses of their own study.

The strengths are obvious. Randomized control trials are considered the gold standard of evidence-based medicine, but they have their weaknesses. Here is what the authors said about the limitations of their study:

  • “Randomized control trials are of shorter duration, whereas longer duration studies might be required to fully capture chronic disease risk.”
  • “Dose-response data were not usually available [from the randomized control studies included in their analysis]. However, larger studies would allow the effect of dose to be assessed.”

There are some other limitations of this study, which I will point out below.

Is This Fake News?

supplements for cardiovascular health fake newsWhen I talk about “fake news” I am referring to the headlines, not to the study behind the headlines. The headlines were definitive: “Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.” However, when you read the study the reality is quite different:

  • In contrast to the negative headlines, the study reported:
    • Folic acid supplementation decreased stroke risk by 20% and overall heart disease risk by 17%.
    • B complex supplements containing folic acid, B6, and B12 decreased stroke risk by 10%.
    • That’s a big deal, but somehow the headlines forgot to mention it.
  • The supplements that had no significant effect on heart disease risk (multivitamins, vitamin D, calcium, and vitamin C) were ones that would not be expected to lower heart disease risk. There was little evidence from previous studies of decreased risk. Furthermore, there is no plausible mechanism for supposing they might decrease heart disease risk.
  • The study did not include vitamin E or omega-3 supplements, which are the ones most likely to prove effective in decreasing heart disease risk when the studies are done properly (see below).

Did The Study Ask The Right Question?

Most of the studies included in this meta-analysis were asking whether a supplement decreased heart disease risk or mortality for everyone. Simply put, the studies started with a group of generally healthy Americans and asked whether supplementation had a significant effect on disease risk for everyone in that population.

That is the wrong question. We should not expect supplementation to benefit everyone equally. Instead, we should be asking who is most likely to benefit from supplementation and design our clinical studies to test whether those people benefit from supplementation.

supplements for cardiovascular health diagramI have created the graphic on the right as a guide to help answer the question of “Who is most likely to benefit from supplementation?”. Let me summarize each of the points using folic acid as the example.

 

Poor Diet: It only makes sense that those people who are deficient in folate from foods are the most likely to benefit from folic acid supplementation. Think about it for a minute. Would you really expect people who are already getting plenty of folate from their diet to obtain additional benefits from folic acid supplementation?

The NIH estimates that around 20% of US women of childbearing age are deficient in folic acid. For other segments of our population, dietary folate insufficiency ranges from 5-10%. Yet, most studies of folic acid supplementation lump everyone together – even though 80-95% of the US population is already getting enough folate through foods, food fortification, and supplementation. It is no wonder most studies fail to find a beneficial effect of folic acid supplementation.

The authors of the meta-analysis I discussed above said that the beneficial effects of folic acid they saw might have been influenced by a very large Chinese study, because a much higher percentage of Chinese are deficient in folic acid. They went on to say that the Chinese study needed to be repeated in this country.

In fact, the US study has already been done. A large study called “The Heart Outcomes Prevention Evaluation (HOPE)” study reported that folic acid supplementation did not reduce heart disease risk in the whole population. However, when the study focused on the subgroup of subjects who were folate-deficient at the beginning of the study, folic acid supplementation significantly decreased their risk of heart attack and cardiovascular death.  This would seem to suggest using supplements for cardiovascular health is a good idea.

Increased Need: There are many factors that increase the need for certain nutrients. However, for the sake of simplicity, let’s only focus on medications. Medications that interfere with folic acid metabolism include anticonvulsants, metformin (used to treat diabetes), methotrexate and sulfasalazine (used to treat severe inflammation), birth control pills, and some diuretics. Use of these medications is not a concern when the diet is adequate. However, when you combine medication use with a folate-deficient diet, health risks are increased and supplementation with folic acid is more likely to be beneficial.

Genetic Predisposition: The best known genetic defect affecting folic acid metabolism is MTHFR. MTHFR deficiency does not mean you have a specific need for methylfolate. However, it does increase your need for folic acid. Again, this is not a concern when the diet is adequate. However, when you combine MTHFR deficiency with a folate-deficient diet, health risks are increased and supplementation with folic acid is more likely to be beneficial. I cover this topic in great detail in my upcoming book, “Slaying The Supplement Myths”. In the meantime, you might wish to view my video, “The Truth About Methyl Folate.”

Diseases: An underlying disease or predisposition to disease often increases the need for one or more nutrients that help reduce disease risk. The best examples of this are two major studies on the effect of vitamin E on heart disease risk in women. Both studies found no effect of vitamin E on heart disease risk in the whole population. However, one study reported that vitamin E reduced heart disease risk in the subgroup of women who were post-menopausal (when the risk of heart disease skyrockets). The other study found that vitamin E reduced heart attack risk in the subgroup of women who had pre-existing heart disease at the beginning of the study.

Finally, if you look at the diagram closely, you will notice a red circle in the middle. When two or three of these factors overlap, that is the “sweet spot” where supplementation is almost certain to make a difference and it may be a good idea to use supplements for cardiovascular health.

Is This A Question Of “Garbage In, Garbage Out”?

supplements for cardiovascular health garbage in outUnfortunately, most clinical studies focus on the “Does everyone benefit from supplementation question?” rather than the “Who benefits from supplementation?” question.

In addition, most clinical studies of supplementation are based on the drug model. They are studying supplementation with a single vitamin or mineral, as if it were a drug. That’s unfortunate, because vitamins and minerals work together synergistically. What we need are more studies of holistic supplementation approaches.

Until these two things change, most supplement studies are doomed to failure. They are doomed to give negative results. In addition, meta-analyses based on these faulty supplement studies will fall victim to what computer programmers refer to as “Garbage In, Garbage Out”. If the data going into the analysis is faulty, the data coming out of the study will be equally faulty. It won’t be worth the paper it is written on. If you are looking for personal guidance on supplementation, this study falls into that category.

 

Should We Use Supplements For Cardiovascular Health?

 

If you want to know whether supplements decrease heart disease risk for everyone, this meta-analysis is clear. Folic acid may decrease the risk of stroke and heart disease. A B complex supplement may decrease the risk of stroke. All the other supplements they included in their analysis did not decrease heart disease risk, but the analysis did not include vitamin E and/or omega-3s.

However, if you want to know whether supplements decrease heart disease risk for you, this study provides no guidance. It did not ask the right questions.

I would be remiss, however, if I failed to point out that we know healthy diets can decrease heart disease risk. In the words of the authors: “The recent science-based report of the U.S. Dietary Guidelines Advisory Committee, also concerned with [heart disease] risk reduction, recommended 3 dietary patterns: 1) a healthy American diet low in saturated fat, trans fat, and meat, but high in fruits and vegetables; 2) a Mediterranean diet; and 3) a vegetarian diet. These diets, with their accompanying recommendations, continue the move towards more plant-based diets…” I cover the effect of diet on heart disease risk in detail in my book, “Slaying The Food Myths”.

 

The Bottom Line

 

You have probably seen the recent headlines proclaiming: “Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.” The study behind the headlines was a meta-analysis of 127 randomized control trials looking at the effect of supplementation on heart disease risk and mortality.

  • The headlines qualify as “fake news” because:
    • The study found that folic acid decreased stroke and heart disease risk, and B vitamins decreased stroke risk. Somehow the headlines forgot to mention that.
    • The study found that multivitamins, vitamin D, calcium, and vitamin C had no effect on heart disease risk. These are nutrients that were unlikely to decrease heart disease risk to begin with.
    • The study did not include vitamin E and omega-3s. These are nutrients that are likely to decrease heart disease risk when the studies are done properly.
  • The authors of the study stated that a major weakness of their study was that that randomized control studies included in their analysis were short term, whereas longer duration studies might be required to fully capture chronic disease risk.
  • The study behind the headlines is of little use for you as an individual because it asked the wrong question.
  • Most clinical studies focus on the “Does everyone benefit from supplementation question?” That is the wrong question. Instead we need more clinical studies focused on the “Who benefits from supplementation?” question. I discuss that question in more detail in the article above.
  • In addition, most clinical studies of supplementation are based on the drug model. They are studying supplementation with a single vitamin or mineral, as if it were a drug. That’s unfortunate, because vitamins and minerals work together synergistically. What we need are more studies of holistic supplementation approaches.
  • Until these two things change, most supplement studies are doomed to failure. They are doomed to give negative results. In addition, meta-analyses based on these faulty supplement studies will fall victim to what computer programmers refer to as “Garbage In, Garbage Out”. If the data going into the analysis is faulty, the data coming out of the study will be equally faulty. It won’t be worth the paper it is written on. If you are looking for personal guidance on supplementation, this study falls into that category.
  • If you want to know whether supplements decrease heart disease risk for everyone, this study is clear. Folic acid may decrease the risk of stroke and heart disease. A B-complex supplement may decrease the risk of stroke. All the other supplements they included in their analysis did not decrease heart disease risk, but they did not include vitamin E and/or omega-3s in their analysis.
  • If you want to know whether supplements decrease heart disease risk for you, this study provides no guidance. It did not ask the right questions.
  • However, we do know that healthy, plant-based diets can decrease heart disease risk. I cover heart healthy diets in detail in my book, “Slaying The Food Myths.”

 

For more details, read the article above.

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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