July 6, 2016

Director's Letter

Carole Baggerly

Director, GrassrootsHealth

We CAN'T WAIT!

to Move Research into PRACTICE

There are many research projects going on with pregnant women using vitamin D supplementation that is TOO LOW to help them based on demonstrable evidence from randomized trial data. Protect our Children NOW! is a project based on research that shows conclusively that 40 ng/ml (100 nmol/L) is a minimum level needed to maximize the reduction in risk for preterm births, preeclampsia and many infections during pregnancy.

As I have approached a number of hospitals about doing this project with their pregnant women, I continue to hear:

"NO! It will interfere with our research projects." (They are giving what is now 'standard of care', 600 IU/day, to the pregnant women.) The research community has taken over public health! Can you imagine knowing that 600 IU/day could actually leave women at a higher risk of a preterm birth and, still defend the research? But, there is a dilemma - what do you do when you're in the middle of that research? With millions of dollars and knowledge in the pipeline ...This is truly a major, new dilemma and a terrible plight for these researchers.

How can we redesign research questions so that we are not harming a population by doing research?! What research questions can we ask that are beneficial? How can we MOVE faster in all fronts after we have seen a result?

There was a recent challenge as to whether vitamin D was good for you--ALL the research studies used in that paper came from the widely esteemed Cochrane Review. For a study to be included in the Cochrane Review however, there has to be a 'placebo' group with 0 (zero) intake. So, a number of the valid studies done with pregnancy were not allowed to be included! But, the bigger question is how can you ethically have a zero intake of a nutrient (any nutrient) for a trial?

We have major problems with the methodology of nutrient research at this time.

Question #1

Are there guidelines for how to do RCT's with nutrients?

Dr. Robert Heaney defined guidelines last year with his paper, Guidelines for optimizing design and analysis of clinical studies of nutrient effects.

The IMPLEMENTATION of these guidelines has not taken place. There are too many trials where, for example, there is no baseline measure of vitamin D. Further, there are many where the dosages are not large enough (based on prior research) to make a difference! Yet, the results of these trials get published and, generally come back with 'no benefit'. If you are familiar with the guidelines, this is not at all surprising.

Question #2

With vitamin D, the key biological measure is the serum level, 25(OH)D. How can we make sure analysis is done with respect to serum level, and not treatment groups?

The reporting methodology of most trials is by treatment group, i.e., how much someone is taking. Due to the widely varying response rate of vitamin D intake, you could have a "high dose" participant with low response to vitamin D skew the results. (We have shown that with our own D*action research.) Analyzing by treatment group hides the results from researchers and, from the health community. It's time for the reporting methods to change.

Question #3

When are RCT's appropriate with nutrients? Where/when
should we be using other methods?

RCTs have a place, as long as the control group is still maintaining the IOM's recommendation for vitamin D. Barring their long timeframe and costs and using Heaney's criteria they could show results.

But is an RCT the only way to demonstrate results that are scientifically credible? Two researchers this week say no, as you may read below.

Evidence and Action

This month's news will address these questions so that you can have the evidence YOU need to take appropriate action! We will be addressing

Evidence based medicine: what it is and what it isn't
The Heaney Criteria for nutrient clinical research--how can you use it to evaluate what you read
Cancer and Vitamin D--what type of evidence do we have, what actions are feasible
Evidence & Action--what do we need to move forward safely and, rapidly for public health benefit?

Onwards!

Carole

Carole Baggerly

Director, GrassrootsHealth

A Public Health Promotion & Research Organization

Moving Research into Practice NOW!

Are we Ready for Vitamin D?

Evidence Based Medicine

Evidence based medicine: what it is and what it isn't

David L. Sackett et al.

Research and Development Centre for Evidence Based Medicine, Oxford

British Medical Journal

January 1996

Read paper

About David L. Sackett

David Lawrence Sackett (November 17, 1934 - May 13, 2015) is known as the pioneer of evidence based medicine. A member of the Canadian Medical Hall of Fame, he has authored many papers and books included his best known textbooks - Clinical Epidemiology and Evidence Based Medicine. His well-known research included using aspirin to help at-risk stroke and heart-attack patients, surgery to repair hardened arteries for stroke prevention, and de-bunking a popular bypass surgery that was doing more harm than good for stroke-prone patients.

He was a Principal Investigator for many randomized clinical trials (RCTs), and even wrote and taught about how they should be designed, conducted, and reported. Sackett appreciated the importance of staying on top of the latest medical discoveries - even going back to complete a second residency 20 years after his first.

What is evidence based medicine?

"Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients."

This means that practitioners make decisions or changes to their standard of care based on multiple sources of information/evidence including:

medical training
clinic/practice experience
reading relevant research

Sackett discusses the need to balance clinical expertise with external evidence. If doctors are too set in the ways of their medical training, they risk not providing the best care for their patients. If they change their methodologies too often and ignore experiences from their practice, they may not be applying new information optimally for their patients.

Do medical practitioners realistically have time to scour external sources? In 1996 Sackett estimated clinicians would need to read 19 articles per day (365 days/year) to keep up with medical advances, however the time available for reading medical journals, according to surveys of self-reported reading time, was less than one hour per week.

Evidence based medicine is not always based on RCTs

"Evidence based medicine is not restricted to

randomized trials and meta-analyses."

Sackett believes you should track down the best external evidence for the question at hand. Reading the editorial from Garland below, you can see that for public health initiatives, this is almost never achieved by RCTs. Sackett words it this way, "some questions about therapy do not require randomized trials... or cannot wait for the trials to be conducted."

How does this apply to vitamin D and overall health?

GrassrootsHealth now has five free CME courses available online for practitioners to gain valuable external information on vitamin D as quickly as possible. After applying this information to change the standard of care in their practice, clinicians have told us that they then gained additional insights into its effectiveness. Dr. Coimbra's practice in Brazil, where he treats his MS patients with high dose vitamin D, is a great example of this evidence based medicine. Last week, we reported on a VA center in the south that uses vitamin D to help patients with chronic pain. The Medical University of South Carolina has changed its standard of care for all pregnant women to include vitamin D testing and supplementation.

Read Sackett's comments

Scientist Editorial

Cedric Garland, Dr.P.H., FACE

Professor Emeritus - University of California San Diego Department of Preventive Medicine

Dr. Garland is a Principal Investigator for D*action. He is convinced that a world replete with vitamin D (from regular, moderate sun exposure and/or vitamin D3 supplementation) would see drastically reduced incidence of breast, colorectal, and 12 other cancers including brain tumors and adult forms of leukemia; and types 1 and 2 diabetes.

He has spent over 35 years researching vitamin D, cancer and diabetes using epidemiology. We asked him to comment on the recent news, using Cochrane Review data, that vitamin D was not effective.

Dr. Garland's editorial:

Most public health initiatives are not suited to randomized controlled trials (RCTs)

Cochrane reviews of RCTs are suitable for summarizing tests of drugs that act quickly, such as antibiotics. But they are usually worthless for confirming problems and solutions in public health. In this field, natural experiments and observational studies usually are the ONLY way to detect associations. There are only a few public health interventions in history that were tested in formal RCTs. RCTs are very expensive, costing at least 10X as much as observational studies. They waste time, potentially 10-20 years, while victims die. Observational studies usually can be done in 1-2 years, as nested case-control studies in cohorts.

Public health action # 1 - smoking in public

An RCT was NOT used as evidence to associate active smoking with (1) lung cancer, (2) ischemic heart disease, or (3) bladder cancer. Secondhand (passive) smoking was found to cause heart attacks (Garland et al. 1985) without an RCT. Discovery of the association between passive smoking with fatal heart attacks in Rancho Bernardo, California led to bans on smoking in restaurants and other public places. We couldn't have exposed people to tobacco smoke to see if they got heart attacks. So RCTs played no role in this public health advance, and could not. Bans on smoking in public places have become common worldwide since 1985. Rates of fatal ischemic heart disease have continued to drop.

Public health action # 2 - neonatal blindness

Most discoveries in preventive medicine and public health have been made by a process of observation and inference. The RCT is a last step, and is often skipped. It is not obligatory. At times RCTs even have been misleading.

Another example is detection of the cause of neonatal blindness in the US, which was due to incubators with too high a partial pressure of oxygen. When the oxygen pressure was too high, infants did not adequately vascularize their retinas enough to allow vision under the normal pressure of oxygen outside the incubator (about 160 mmHg or 2.2 pounds per square inch). When these babies left the incubator and its high partial pressures of oxygen, they could not see. Sadly the condition also caused scarring near the retina that blocked transmission of light, and was usually irreversible. This condition was named retrolental fibroplasia (RF).

RF was more common in black infants, who were more likely than white infants be premature. Kate Campbell, MD, a pediatrician from Australia reported that they did not hook oxygen tanks to incubators in Australia, and they had no epidemic of infant blindness. She thought these two facts probably were related. Two British doctors proposed an association, noticing that blind babies were more commonly born in the highest tech hospitals, and there were many fewer blind babies per 100 births in low-tech hospitals. High-tech hospitals used oxygen in their incubators while low tech hospitals often did not.

An RCT was eventually done in an effort to prove that Australian's and British doctor's hunch was wrong. The RCT totally missed the association, apparently due to procedural problems. The authors claimed that the associations noticed by the doctors from outside the US were wrong, and that high-pressure oxygen should continue to be used. It became a rather bitter fight. At some point later, an RCT conducted with more careful procedural safeguards eventually confirmed the association.

After a time of uncertainty, some hospitals reduced the partial pressure of oxygen in their incubators, and the neonatal blindness epidemic in those hospitals virtually disappeared.

In retrospect, the natural experiment that resulted from some US hospitals using too much oxygen and Australian hospitals using none was for years the only correct source information about oxygen toxicity as the cause of RF. The first RCT yielded bogus information. At its high point of incidence in 1949, RF accounted for half the blindness of US babies. One of the most famous of the 12,000 estimated cases of RF during 1941-1951 in the US and Britain was soul singer Stevie Wonder.

There are many such examples.

- Cedric Garland

Editor's Letter

Susan Siljander

Marketing Director, GrassrootsHealth

Both the editorials from Sackett and Garland are well-thought out, interesting points of view by brilliant and passionate scientists. Both want what is best for the public. Both are pioneers in their field. Both want to shake the world into pragmatism. Could we just make a sensible decision here?

There is enough evidence about vitamin D. Vitamin D is not costly. Vitamin D can be measured and monitored for safety.

Meanwhile...

The world is in a health crisis with cancer, diabetes, preterm birth, etc..

Anyone see the connection? We know you do and hope you forward this news onto your healthcare providers, print it out for your lunch rooms at work, pin it to your church cork board, just don't litter it on the beaches.

Have a great week!

Susan Siljander

Marketing Director, GrassrootsHealth

A Public Health Promotion & Research Organization

Moving Research Into Practice NOW!

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Your participation in this project provides information for your answers to D questions and helps fund the GrassrootsHealth projects.

Understanding the Heaney Nutrient Guidelines

Interpretations on controversial research

View web page

Interested in other at-home nutrient testing?

Interested in providing more detailed health information - to provide more detailed research?

We want to hear from you!

We will be sending you a short questionnaire very soon about some new research within the GrassrootsHealth cohort with other nutrients, offering additional blood tests. We'd like to know what you're interested in, why, how we can help you have an informed experience!

Stay tuned...

Evidence based medicine: what it is and what it isn't

David L. Sackett et al.

Research and Development Centre for Evidence Based Medicine, Oxford

British Medical Journal

January 1996

Read paper

Evidence based medicine: does it make a difference?

Bejamin Druss et al.

Emory University

British Medical Journal

January 2005

Read paper

David Sackett: The father of evidence based medicine

The Globe and Mail

May 25, 2015

Read Story

Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study

Sharon L. McDonnell, et al.

PLOS One

April 2016

Read Paper

Post-hoc analysis of vitamin D status and reduced risk of preterm birth in two vitamin D pregnancy cohorts compared with South Carolina March of Dimes 2009-2011 rates

Carol L. Wagner, et al.

The Journal of Steroid Biochemistry and Molecular Biology

October 2015

Read Paper

Incidence rate of type 2 diabetes is >50% lower in GrassrootsHealth cohort with median serum 25-hydroxy-vitamin D of 41 ng/ml than in NHANES cohort with median of 22 ng/ml

Sharon L. McDonnell, et al.

The Journal of Steroid Biochemistry and Molecular Biology

July, 2015

Read Paper

Post-hoc comparison of vitamin D status at three timepoints during pregnancy demonstrates lower risk of preterm birth with higher vitamin D closer to delivery

Carol L. Wagner, et al.

The Journal of Steroid Biochemistry and Molecular Biology

April 2015

Read Paper

Letter to Veugelers, P.J. and Ekwaru, J.P., A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D.

Robert Heaney, et al.

Nutrients

March 2015

Read Paper

Quantifying the food (and non-food) sources of basal vitamin D input

Sharon L. McDonnell, et al.

Journal of Steroid Biochemistry and Molecular Biology