Vitamin D3 supplemental intake as a ratio of bodyweight - for people of all ages.  (The suggestion of an electronic technician.)

Robin Whittle rw@firstpr.com.au  28th November 2020
(First established 2020-11-08.)

These ratios are intended to be authoritative recommendations, but they are not peer-reviewed or, yet, supported by any MDs or researchers

You are reading something written by an electronic technician, as a suggestion for what would be the best way of advising people on how much vitamin D to supplement, as a ratio of bodyweight.

This is a fundamentally different way of recommending vitamin D supplementation levels from the age-based frameworks normally employed by governments and professional organisations, such as the Endocrine Society.

This suggestion, or something along these lines - if accepted by nutritionists, MDs, researchers and health authorities -  would replace complex existing conventions with simple guidance which will work well for everyone, in all nations whose bodies are all shapes and sizes - from newborns to the elderly.

The text below is written as a draft of what I imagine an authoritative nutritional recommendation would be.   If you are a nutritionist, doctor, nurse or researcher and would like to fully or partially support what I suggest here, please let me know, since I would really appreciate this.

Until and unless some such qualified professionals state publicly that they partly or fully support what follows, please remember that you are reading the best efforts of an electronic technician in the important field of human nutrition.

The details of how I chose these ratios are on a separate page:

a-ratios/


#grh
There is a ratio-based vitamin D calculator at Grassroots Health:

https://www.grassrootshealth.net/project/dcalculator/

A second page here analyzes the output of this calculator:

b-grh/

The Grassroots Health calculator's base and upper ratios seem to be:

1.35 to 3.6 micrograms of D3 a day, per kilogram bodyweight.
with rounding up or down to the nearest 25 micrograms = 1000 IU
AND with maximum quantity = 0.25mg = 250 micrograms =  10,000 IU.

A Grassroots Health chart states that for a population of people with an unsupplemented 25OHD level of 20ng/ml, supplementary D3 of 69 IU per kg bodyweight will raise their 25OHD levels so that 90% of them attain at least 40ng/ml.  This is 1.725 micrograms of D3 a day, per kilogram bodyweight.

The next section contains my suggested ratios and the section which follows this contains some additional notes, including about how my suggestions differ from existing approaches to recommending vitamin D supplemental levels. 

A section below #iom is a discussion of how the Institute of Medicine (IOM) in 2010 and 2011, completely miscalculated the Recommended Daily Allowance of D3 for 25OHD levels of 20ng/ml, and how, despite this failure which has never been corrected, the IOM recommendations from those years are still the foundation for most government vitamin D supplementation recommendations.


The suggested ratios and the notes which go with them

My suggestion for the core recommendation text is in the box.  Some other notes and graphs follow.

There are two pairs of ratios, one for people with normal and overweight body types and a second pair for people suffering from obesity.  The first ratio of each pair is the base ratio and the second is the upper ratio.


For people with normal and overweight body types:

1.8 to 3.6 micrograms of D3 a day, per kilogram bodyweight.
(72 to 144 IU/kg.)

0.82 to 1.65 micrograms of D3 a day, per pound bodyweight.
(33 to 66 IU/lb.)

Thus, an average weight (70kg, 154lb) Caucasian adult's base supplemental intake is 0.125 milligrams (5000 IU) a day and their upper recommended intake is 0.25mg (10,000 IU) a day.  (The average bodyweight [WP] of Asians is generally less than this, so less vitamin D3 would be required for an average weight Asian adult.)


For people suffering from obesity:

2.5 to 5.0 micrograms of D3 a day, per kilogram bodyweight. (100 to 200 IU/kg.)

1.14 to 2.28 micrograms of D3 a day, per pound bodyweight.
(46 to 92 IU/lb.)


Morbidly obese people should seek medical care and probably supplement with higher ratios.

BMI is not the best indication of obesity, which it overestimates in tall people.  In order to correctly identify obesity in children, and to avoid wrongly classifying tall overweight people, obesity should be determined by medical examination, waist circumference or other recognized methods suitable for children and adolescents. 

The base and upper ratios provide a range of supplemental quantities which are all safe and beneficial. Since the ratios are based on observations of people who had some high elevation sun exposure, generally white skin and some level of vitamin D3 in food and multivitamins, people who have little or no high elevation sun exposure and/or who have dark skin and/or who not eat oily fish or take multivitamins would be well advised to choose a ratio somewhat above the base ratio.   The same applies to overweight people who border on an obese diagnosis: choose a base ratio closer to 2.5 micrograms/kg than 1.8ug/kg.


People with reduced fat absorption - such as resulting from Roux-en-Y gastric bypass surgery or other conditions - should initially double the D3 supplemental intakes specified above and seek medical advice based on blood tests to ensure their long-term vitamin D sufficiency.

People whose ultraviolet B skin exposure generates significant vitamin D may require less than these intakes.  However, these upper recommended intakes, even with high levels of sun exposure, are a third or less of quantities which might, after many months, lead to risk of toxicity.

These recommendations apply to all people without acute medical conditions – newborns to the elderly – except that infants substantially breastfed by vitamin D replete mothers need no supplements.

People with a variety of immune system diseases may benefit from vitamin D intakes in excess of those suggested above, including intakes which would cause toxicity in some people.  This should be done under medical guidance, such according to the The Coimbra Protocol for multiple sclerosis.

Vitamin D3 interacts minimally with other nutrients.  Taking D3 supplements towards the end of a meal may be a good approach, since this maximises the time the D3 spends in the upper small intestine, where fat absorption is most effective.

Vitamin D supplementation may be contraindicated in some rare lymphomas and in granulomatous illnesses such as sarcoidosis.    Medical supervision and guidance on vitamin D supplementation is necessary for both conditions, perhaps with supplemental vitamin K2 and with reference to research which indicates that sarcoidosis patients do better with vitamin D and calcium supplements: 

Calcium and Vitamin D in Sarcoidosis: Is Supplementation Safe?
Lieke S Kamphuis, Femke Bonte-Mineur, Jan A van Laar, P Martin van Hagen, Paul L van Daele
Journal of Bone and Mineral Research 2014-04-18
https://doi.org/10.1002/jbmr.2262  (Paywalled.)
https://sci-hub.tw/https://doi.org/10.1002/jbmr.2262


According to my interpretation of the Ekwaru et al. 2014 article from which I derived these ratios, a  population supplementing with base intake quantities will raise their 25OHD levels to an average of about 50ng/ml, with half the people having levels below this.  The upper supplementation levels will achieve average levels of about 60ng/ml, with only a small proportion of people having levels below 30ng/ml.

The subjects of the Ekwaru research all, to some degree or other, gained D3 from UVB skin exposure, food and probably multivitamins which were not included in the formal supplemental values reported.  These intakes were not calculated by the researchers, but were presumably typical of the Canadian adult population.  Strictly speaking, the ratios I derived are applicable only to people who also have similar such sources of D3.   However, these intakes are small compared to the intakes the ratios recommend.  So the ratios should work well even for people who have very little other sources of D3.

Today, many governments are contemplating COVID-19 vaccinations for the majority of their populations, with lockdowns, social distancing and other unsustainable suppression measures continuing well into 2021.

Similarly comprehensive, voluntary, vitamin D repletion using these ratios will be far less expensive and much safer than vaccination, with no need for medical staff, complex administration or visits to remote areas.  It will also be far more effective against COVID-19 and have numerous other health benefits.  This is nutritional support, not a drug or medical intervention.

COVID-19 severity, viral shedding and transmission

Please see the main page  for infographics and links to research on vitamin D and COVID19.

Vitamin D replete individuals - those with 40ng/ml or more 25OHD - have a somewhat reduced chance of coronavirus infection for any given viral insult. 

If infected, their symptoms will be greatly reduced and the risk of lasting harm and death will be a small fraction of what would be with unsupplemented 25OHD levels.  More importantly still, vitamin D replete people who are infected will shed viruses for fewer days, and in much smaller quantities than those who are not




(Adapted from Figure 1 of https://www.jci.org/articles/view/138759 .)

This last effect is the most significant for ending the pandemic, and the most important in terms of personal responsibility.

Population-wide vitamin D repletion aiming at average vitamin D 25OHD levels of around 50ng/ml (125nmol/L) will quell COVID-19 transmission and end the pandemic, in all seasons, without lockdowns, social distancing or masks.  

The summer average 25OHD levels of UK white people is around 24ng/ml.  This is sufficient to greatly suppress the transmission and symptom severity of both COVID-19 and influenza.   So it is reasonable to assume that population-wide supplementation to achieve average 25OHD levels twice this will result in very low rates of transmission all year round, and similarly low risk of severe symptoms for those few who are affected - for both COVID-19 and influenza.

Furthermore, this approximately 50ng/ml average level of 25OHD will suppress transmission no matter how the current hundreds of strains of SARS-CoV-2 and influenza continue to mutate. 


#25plusD3

25plusD3 - my suggestion for a D3 & 25OHD calcifediol combination supplementation treatment for COVID-19, severe influenza and sepsis

This is a terse account of the fuller proposal at https://aminotheory.com/cv19/#25plusD3 , for immediate adoption in the current COVID-19 crisis, and also for severe or potentially severe influenza as well as for sepsis.   Here I discuss my suggested 25plusD3 protocol in the future context of the population generally robustly supplementing D3 to attain healthy, ca. 50ng/ml 25OHD vitamin D levels.

This is a suggestion for treating severe or potentially severe COVID-19 in light of the resounding success of the Cordoba 0.532mg oral 25OHD calcifediol trial (Castillo et al. 2020 - see links and discussion at my other website: https://aminotheory.com/cv19/#2020-Castillo and the link and discussion below) and in the light of the success of earlier trials of bolus oral D3.

In the generally high (average 50ng/ml 25OHD) vitamin D future I propose, those few people who suffer serious COVID-19 symptoms can be treated with the MATH+ protocol [https://covid19criticalcare.com], plus a loading dose (bolus dose) of D3 and 0.5mg to 1.0mg so of 25OHD calcifediol to achieve much more rapid and complete recoveries than are achieved in many hospitals today. 

https://patents.google.com/patent/WO2016124724A1/

Effect of Calcifediol Treatment and best Available Therapy versus best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical study
Marta Entrenas Castillo et al. Journal of Steroid Biochemistry and Molecular Biology 
https://www.sciencedirect.com/science/article/pii/S0960076020302764

Of the Cordoba trial's  26 control patients, 13 (50%) needed intensive care and 2 (7.7%) died.  Of the 50 patients who received 25OHD calcifediol, 1 (2%) required intensive care and none died.

A bolus dose of, for instance 12.5mg (500,000 IU) D3 over 5 days would take several days to to a week to  raise 25OHD levels on its own, but will sustain these levels for a few weeks at least.  So an initial 0.5mg 25OHD calcifediol dose and a bolus D3 dose, both at the earliest opportunity, will raise 25OHD within hours and for the next few weeks.  The D3 itself, without conversion in the liver to 25OHD, directly stabilises the endothelial cells which line the blood vessels  [Gibson et al. 2015] - the destruction of which in severe COVID-19 causes the hypercoagulative state of the blood, which causes microembolisms and larger blood clots in all organs. 



https://patents.google.com/patent/WO2016124724A1/

My 25plusD3 suggestion will only be a bona-fide protocol after some MDs adopt it. 

There is an urgent need for better treatment of severe or potentially severe COVID-1.  There is no time or need for RCTs etc.  People are being harmed and are dying all over the world right now, and one doesn't have to do a lot of research reading to conclude reliably that both components of what I propose: ~0.5mg to 1.0mg 25OHD AND a robust bolus dose of D3, both at the earliest opportunity are safe and beneficial.  The two complement each other very well, as I discuss in the abovementioned section at my other website.

As of mid-November 2020, Cordoba-style Co25OHD dosing OR bolus D3 are part of the MATH+ protocol.  I believe they should both be used together, but this is a most welcome development.  Full details at https://aminotheory.com/cv19/#25plusD3 .

More on severity, shedding, transmission and other similarities between COVID-19 and influenza

The same principles of reduced severity, shedding and transmission apply also to influenza: with average 25OHD levels of 50ng/ml, the flu virus will hardly spread at any time of year due to low viral shedding -  and would rarely cause serious harm.  Those few with severe symptoms could be treated much better than at present with the D3 and 25OHD (combination cholecalciferol and calcifediol therapy) as just described.  There would be no need for flu vaccines.

SARS-CoV-2 / COVID-19 and influenza share a striking similarity in the degree to which their symptom severity and transmission rate (presumably largely due to viral shedding rates) rise in the winter and spring period for countries far from the equator.  In India, the hot, wet, cloudy monsoon [WP], keeps most people indoors and out of direct sunshine.  Vitamin D levels drop, COVID-19 surges and with the end of the approximately June to September monsoon this year, new COVID-19 case numbers which had been rising to mid-September, have since (to early November) been dropping just as rapidly as they rose:  https://ourworldindata.org/coronavirus/country/india?country=~IND(See also:  Implications of Monsoon Season & UVB Radiation for COVID-19 in India Rahul KM, Lennart Kraft  medRxiv .)

Both of these observations can be reliably assumed to be due mainly or wholly due to the decline in vitamin D levels caused by reduced direct high-elevation sun exposure.  There is little evidence linking seasonality of influenza or COVID-19 to temperature, humidity or behavioural changes, though these and numerous other factors including lockdown, social distancing and masks surely affect the spread of the diseases to some extent.

On this basis it is reasonable to assume that the symptom severity of both diseases depends very much on the weakened and/or dysregulated immune responses which naturally occur in all people when they 25OHD levels are low, well below the 40ng/ml or higher range now recognised as being essential for immune system health.

Another striking similarly between the two diseases is how influenza severity - and presumably total viral shedding - is driven to a high degree by obesity, which is now well known (see my page https://aminotheory.com/cv19/obesity/ which lists risks including lower D3 conversion to 25OHD, and ectopic ACE2-expressing adipocytes in the alveolar tissue)  to be a high risk condition for those suffering from COVID-19:

Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic
Livio Luzi and Maria Grazia Radaelli, Acta Diabetologica 2020-04-05
https://dx.doi.org/10.1007%2Fs00592-020-01522-8

Incidence of the extreme immune dysregulation disorder sepsis - which according to the following analysis causes 20% of all deaths worldwide - will be significantly reduced when most of the population supplements with sufficient vitamin D3 to raise average levels by a factor of three or four to about 40ng/ml.

Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study
Kristina E Rudd et al. The Lancet  2020-01-18

https://doi.org/10.1016/S0140-6736(19)32989-7

Sepsis, severe COVID-19 and severe influenza all involve extreme levels of immune dysregulation.  Likewise the childhood and adolescent conditions Kawasaki disease and Multisystem Inflammatory Syndrome: https://aminotheory.com/cv19/#2015-Stagi .)

The success of the Cordoba calcifediol trial can reasonably be extrapolated to the prospect of treating sepsis, KD and MIS patients with similar oral calcifediol amounts to raise their 25OHD and so improve autocrine signaling and immune system regulation within a few hours.  

Evidence for the effectiveness of substantial bolus D3 doses in sepsis comes from a 2015 RCT in which a 12.5mg (500,000 IU) D3 bolus dose over five days halved the average length of hospital stay from 36 days for the control group to 18 days for this supplementation group.  This supplementation raised the average baseline 25OHD level from 20 to 53ng/ml on day 7.   Half the amount of D3 over five days reduced the average hospital stay to 24 days:

High dose vitamin D administration in ventilated intensive care unit patients: A pilot double blind randomized controlled trial
Jenny E Han et al. Journal of Clinical & Translational Endocrinology  2016-05-05

https://doi.org/10.1016/j.jcte.2016.04.004


Numerous other chronic and acute diseases are caused, at least in part, by chronic inflammation.  These conditions include both types of diabetes, auto-immune conditions and neurodegenerative disorders including Alzheimer's and Parkinson's diseases.  These and other diseases involving chronic inflammation can be expected to become less prevalent with the end of the Vitamin D Deficiency Pandemic.

Vitamin D need not be taken every day, so larger supplemental intakes every 5, 7 or 10 days are as effective as daily intakes.  As mentioned above, D3 itself, without conversion to 25OHD, stabilizes endothelial cells throughout the body.  This relatively recent discovery implies that the interval between D3 capsules should be no longer than a week or so.  Longer intervals between supplemental intakes would probably allow liver conversion of D3 to to substantially deplete the circulating D3 which endothelial cells depend upon.

Dietary Vitamin D and Its Metabolites Non-Genomically Stabilize the Endothelium
Christopher C. Gibson et al. PLoS One, 2015-10-15 
https://doi.org/10.1371/journal.pone.0140370

Prioritizing those most in need in a time of crisis and the urgent need for new vitamin D3 cholecalciferol factories

Engineers do not debate the merits of fully charged batteries, or of tanks filled with uncontaminated fuel.  It is standard practice to supplement indoor-housed agricultural animals with nutrients, including vitamin D3.

Arnold L. Hirsch describes vitamin D3 production in his 2011 book chapter Industrial Aspects of Vitamin D. 

Industrial Aspects of Vitamin D
Arnold L. Hirsch Chapter 6, Vitamin D, 3rd Edition, 2011, ISBN: 9780123819789 
https://sci-hub.se/10.1016/B978-0-12-381978-9.10006-X

In 2010, 77 tonnes of less refined D3 was manufactured for agricultural feed and 20 tonnes in a highly purified form for human consumption.  Today, pharma-grade D3 costs about USD$2,500 per kilogram ex-factory, for instance this AliBaba seller.  In November 2020 I learned, from an interview with Satish Verma, MD of Fermenta Biotech in India, that approximately 35 tonnes of pharmaceutical grade D3 is produced per year, for human food fortification and for supplements such as capsules and drops for infants.  Approximately 4 times this D3 is also produced, in a less refined form, for agricultural animal feed.

Depending on levels of obesity, full adoption of the above recommended D3 intakes would lead to average daily intakes of about 1/6000 of a gram per person per day.   This is about 60kg per million people per annum, reflecting the fact that humans need about one part per million body weight of D3 per year.  At current prices the required pharma grade D3 would cost USD$150,000 per annum per million people.   Since this would save hundreds of millions or perhaps billions of dollars worth of health costs per year, this represents an astronomically high return on investment.

Most D3 production is in China and India.  The output of those factories is insufficient for the needs of these countries' people.  So all countries with the capacity to do so should build D3 factories with utmost haste.   I can't rule out innovative techniques, but unfortunately it probably takes at least a year to build a D3 cholecalciferol factory using established techniques.   So I think that for the northern winter of late 2020 and early 2021, we are going to have to draw down stocks of human D3 and use some animal feed D3, which is generally made into a spray dried powder form with 1.25% D3.   I assume that this is perfectly fine for humans, since it is fine for the animals we eat.

The starting compound is cholesterol, extracted from wool fat.  This is converted in several steps to high purity 7-dehydrocholesterol, which is then dissolved in a hydrocarbon solvent.

Special kilowatt sized mercury vapor lamps with iron doping are required to produce the precise ~297nm UVB wavelengths which are required.  The hydrocarbon solvents used for the reaction and purification steps are largely recycled but the process is onerous, since the solvents are volatile, highly inflammable and there are multiple stages of distillation to recover the D3 from the other compounds present.

In the initial stages of the country-wide programs which would eliminate most or all of the serious threats posed by both COVID-19 and influenza, vitamin D3 will be in short supply, so the recommended intakes will not be achieved for all people until new factories are operational.

During this time it would be best to recommend full daily intakes and perhaps loading doses up to 60 days equivalent for the people in greatest need, starting with all hospital patients and healthcare workers.  These people include residents and staff of aged care homes and of correctional facilities, police, emergency service workers and the armed forces.  Transport workers and those whose work is most critical to governments and utilities would come next.  The elderly and those with black or brown skin should also be prioritized since they are most likely to have low levels of D3 production in their skin.

These recommended D3 intake ratios are easily applied to all people, of all countries, without reliance on medical resources.  They supersede existing guidelines, which typically set a particular intake for broad groups of people, such as those aged 1 to 17.  Production and distribution of D3 capsules and drops for infants, with clear multi-lingual guidance on correct dosage, should be left to the private sector so people can choose the products which most suit them.

Governments should support D3 repletion with multilingual information for the public, healthcare workers and pharmacists.  Limits on per-capsule quantities, such as 0.025mg (1000IU) in Australia, should be lifted so average weight people can purchase capsules which match the weekly quantities recommended above, such as for a 90kg person using 2.7ug/kg per day: 1.7mg (68,000IU). 

With mass production of smaller numbers of higher capacity capsules, there is great scope for reducing the annual cost per person of D3 supplements.   For instance, at present, in Australia, with five 1000IU capsules a day, the annual cost for an average weight adult using the base ratio, using the least expensive capsules available is ( (365 * 5) / 400) = 4.6 bottles @ AUD$14 each = AUD$64.40 per annum.   This is good value, but involves five capsules a day, when one a week would be more convenient and less expensive.  The total amount of D3 in this year's supply at 0.125mg (5000 IU) a day is 0.046 grams, which has an ex-factory cost of about US 12 cents, or AUD$0.17.

The public should be informed and reassured that the recommended intakes are safe and beneficial and that there is no reason to exceed these intakes except under medical advice. 

25OHD testing is unavailable in many parts of the world.  There is no need to test the blood vitamin D levels of healthy people in any country.  The cost and medical effort such tests involve would be better directed to other health and nutrition needs.  The supplemental D3 quantities described above support the levels of an essential nutrient which is very well researched and known to have large safety margin between the amounts required for good health and those higher amounts which might, for some people, result in toxicity.   

The above is a suggested way of specifying nutritional support, which involves no medical supervision or testing, because it it is not medicine, and does not involve drugs or their risks.

There are other common nutritional deficiencies which deserve concerted government effort to correct.  Zinc deficiency has been implicated as a causal factor in severe COVID-19: https://www.medscape.com/viewarticle/938793 .

Omega 3 fatty acids, vitamin C, B vitamins (especially B12 for older people) and iron all deserve such attention.  Please see Hira Shakoor et al. 2020-08-14: Be well: A potential role for vitamin B in COVID-19.  Vitamin K2 is found in many foods, but its deficiency has been implicated in COVID-19 severity (Simon Goddek 2020-08-04).  It is vital for calcium-bone metabolism and coagulation regulation.  Adequate vitamin K2 is thought to reduce the risks of hypercalcemia from greatly excessive D3 supplementation. 

These other nutrients are worthy of investment regarding research, education and population-scale repletion.  However, none of them come close to vitamin D, which is needed by so many cell types, in such small quantities, and for which global repletion would constitute a profound revolution in human health.

How these bodyweight ratio D3 supplemental suggestions differ from conventional ways of recommending vitamin D supplementation

Governments and other organisations which make recommendations for vitamin D supplemental intake quantities do not, as far as I know, define those quantities as a ratio of bodyweight - even though this is the simplest form such recommendations could take while remaining applicable to all people.   An exception is Grassroots Health, who use ratios in their calculator and in an intake recommendation chart mentioned above #grh.

As far as I know, all these government recommendations make specific quantity recommendations, such as for a basic intake and a maximum safe intake, according to classes of people in which the population is divided into categories by age and other characteristics.

This is exemplified by the following table which attempts to generalize the divisions and quantities used by most developed nations.



This table is from:

Official recommendations for vitamin D through the life stages in developed countries
Samantha Kimball and Michael Holick  2020-08-20
Eur J Clin Nutr (2020).

https://doi.org/10.1038/s41430-020-00706-3 (Paywalled.)

https://sci-hub.se/10.1038/s41430-020-00706-3

Many countries base their guidelines on the fatally flawed 2011 work of the US IOM (as discussed below #iom).  The IOM's calculated RDA for vitamin D was less a tenth of the correct figure.  Their RDA figure of 0.125mg (600 IU) is all through their recommendation table, and is used by the USA and many other countries.






The UK government recommends only 0.01mg (400IU for adults).  This tiny quantity is approximately the mass of 2mm of human hair - a gram every 274 years - less than one UK pence worth of vitamin D per year

These conventional approaches (now referring to the generalised table above the IOM one) are inferior to the ratio of bodyweight approach I suggest above in  several ways:

  1. The quantities are generally too low - and at times disastrously low, such as for 17 year olds, and worse still for obese 17 year olds.

  2. Age is used as a proxy for body weight.

  3. People are binned into broad categories according to age, despite the great range of body weights in each category.

  4. The 16 first and second column categories plus 8 upper level columns are overly fussy and not needed.

  5. The maximum level takes no account of obesity.

The suggestions above explicitly state that D3 supplementation is nutritional support, not a medical intervention or anything to do with medicine at all.

The suggestions above also specifically state that 25OHD testing is not required for the general population and furthermore, even when it might be possible to test a significant proportion of the population, that this not be done so that the resources can be used for a better purpose.

This no mass testing aspect of the suggestions above are are, as far as I know, novel.  This may seem radical considering that many doctors today prefer to regularly test their patient's 25OHD, and that a number of new vitamin D promotion schemes, developed or revamped this year due to the COVID-19 crisis, explicitly require initial and perhaps regular testing.   These include:
In order to achieve a very high degree or success in repleting vitamin D all round the world, the arrangements need to be lightweight, applicable to all people, and not rely on expensive infrastructure such as pathology labs which are not available in many countries.


#iom

The IOM's great blunder in calculating the 20ng/ml RDA for vitamin D3 - and why I believe a D3 RDA for achieving 40ng/ml is undesirable

There are a variety of factors holding back official D3 supplemental quantity recommendations from according with our current knowledge of the immune system and the role adequate vitamin D plays in its proper function.

One major problem is that most committees who control such recommendation documents rely on now-discredited guidance from the US Institute of Medicine's 1133 page report.  A central feature of this report, and all the other recommendations which arise from it is that the RDA (Recommended Daily Allowance) for D3 to achieve 20ng/ml (in at least 97.5% of the population, which is the definition of RDA) is 0.015mg (600IU).

The fault in the IOM's calculations was first reported by P. J. Veuglers and J. P. Ekwaru in 2014: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210929/ .

The IOM's blunder was simple and devastating.

In order to find the RDA it is necessary to use the statistical distribution pattern of numerous individual 25OHD levels which result from one or more different supplementation quantities.  By finding a supplemental intake in which the mean and the standard deviation ensured that two standard deviations below the mean resulted in the desired 25OHD level, this ensures that 95% of the subjects' 25OHD levels were within the +/- 2 SD range of the mean, with 2.5% of the individual levels above the +2SD line and 2.5% below the -2SD line.  

Instead of analysing the individual 25OHD levels and supplemental intakes of the individual subjects in all the research studies they were using, the IOM instead analysed the statistics of the averages of each such study!  This distribution of points on the intake vs. 25OHD graph tells us nothing about the 25OHD levels of the individuals in these studies.  So it is impossible to calculate the RDA in this way.  The IOM used the distribution of average levels of trials as if they were the individual levels of a small number of actual people.

In March 2015 Robert Heaney and colleagues revisited the IOM's mistake and performed a proper analysis on their own data set of individual 25OHD values, for subjects taking a variety of supplemental D3 quantities:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377874/ 

Robert Heaney, who was born in 1927, died in 2016 after six decades of research into osteoporosis and other illnesses: https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbmr.2981

They estimated the true 20ng/ml RDA for the cohort on which their dataset was based as:

. . . must be close to 0.175mg 7000 IU per day. . . .

So the IOM's RDA was a factor of 10 or 11 too low.

Robert Heaney and colleague's result was partly due to them correcting for their subject's D3 inputs from UVB exposure, food and any supplements not counted by the research study.   This was done by extrapolating the somewhat curved mean line to the horizontal axis which represents zero 25OHD.  This correction, which the IOM did not attempt, is perfectly valid since the definition of the RDA involves all D3 inputs, including supplements, food and from UVB exposure.

The IOM's work has never been corrected - and to this day forms the basis of vitamin D supplementation guidelines in most countries.

So the IOM's RDA still is a factor of 10 or 11 too low.

This one, simple, statistical error has arguably had extraordinarily destructive repercussions - though by rights it should have been acknowledged in 2014/15 and the whole of the IOM's report revised according to the new knowledge about the 20ng/ml RDA really being about 0.175mg 7000 IU.  

If this error had never been made, of if it had been promptly corrected four years ago, then the IOM's guidance on vitamin D supplementation would have been very different.

In its 2010 and 2011 deliberations the IOM rebuffed submissions to set its target 25OHD level higher than 20ng/ml on account of the demonstrated importance such higher levels have for immune function and other "extra skeletal" (not concerning calcium and bone) aspects of health.   The IOM argued against such evidence and decided to aim for 20ng/ml 25OHD which they, probably correctly, asserted was sufficient to enable the kidneys to produce the very much lower levels (a factor of 1,000 or so) of circulating 1,25OHD calcitriol, which functions as a hormone to regulate calcium and bone metabolism.

Had they chosen a higher target, most likely 30ng/ml, then even with their conceptual error, they would have arrived at a higher RDA than 0.015mg (600 IU).

If the IOM had correctly calculated the 20ng/ml RDA at about 0.175mg 7000 IU,  it is reasonable to imagine that by now the resulting official guidelines in many countries would have lead to much greater general levels of supplementation, and the creation of new factories to meet the few hundred tonnes per year demand for D3 which this would create.

To the extent that this was actually adopted by most people in a given country, we would have seen a revolutionary transformation in general health, with the most dramatic changes including that influenza was hardly transmitted in any season, with few of those infected being harmed.   Before long the IOM's work would come to the top of the pile for consideration for the Nobel Prize for Medicine!

Note that this correct RDA, even though it is only for 20ng/ml, would involve daily D3 intakes much the same as would result from the base ratio I suggest above.   The incidence of sepsis would by now be greatly reduced.  Furthermore, SARS-CoV-2 would not spread very much and would rarely cause serious harm.

Can anyone think of a comparable blunder with such far-reaching consequences?

Instead we now have:

I want to highlight this extraordinary blunder because it is not widely enough known.   I only learned about it in October 2020 and I have been devouring vitamin D research for a year or so.

If anyone thinks my suggested ratios of 1.8 to 3.6ug/kg bodyweight are too high, they should remember that the resulting amounts for a 70kg adult: 0.125mg 5000 IU to 0.25ug 10,000 IU are very close to the 20ug/ml RDA which the IOM should have calculated in 2011.


This raises the question of what the RDA would be for what we now regard as a good 25OHD level: 40ng/ml.

Here is my attempt to calculate not exactly the RDA, but something like it - without the correction for the subjects' non-supplemental D3 inputs from food and UVB exposure.  I did this after deriving the ratios above from the work of Ekwaru et al.  With careful Photoshop measurements of Heaney et al.'s graph, I found that the figure was about 0.278mg (9110 IU) - to which 0.0781mg (3125 IU) for food and other sources should be added to create the true 40ng/ml RDA (0.356 mg = 14,244 IU) for the subjects whose 25OHD levels are represented in this dataset.



When contemplating this potential 0.278mg (9110 IU) amount as if it was the amount "all adults" are told to take, I looked at the top red curve for this intake which is at 110.7ng/ml, predicting that 2.5% of the population would be above this.  This looks borderline problematic to me, for 70kg adults because I guess a few of them would have levels above 150ng/ml, which we are keen to avoid, since it is generally considered the level above which toxicity may become a problem. 

I assume that quite a lot of the high 25OHD distribution is for people with lower than average bodyweights - so I don't think we can advocate anything like "adults" taking this RDA.

Also, the average at this 0.278mg (9110IU) point in the graphs is 75.5ng/ml, which is significantly higher than the 46ng/ml average level of Luxwolda et al. found for traditionally living Maasai pastoralists and Hadzabe hunter gatherers.

This line of enquiry lead me to the conclusion that the RDA concept is fundamentally flawed, at least for vitamin D's 25OHD levels, which exhibit a great deal of scatter.

The RDA idea is noble.  However, with this degree of scatter, the RDA is forced to be so high that the average 25OHD significantly exceeds what we observe in populations in which we believe the 25OHD levels are generally: 46ng/ml.

Part of the scatter is due to the wide bodyweight variation among adults.  This is the primary reason for the RDA concept being fundamentally broken.   There are also questions of body morphology where excess adipocytes in obese people, from all accounts, soak up a lot of the 25OHD and never return it to the bloodstream - and where the 25-hydroxylase enzyme in the liver is downregulated, reducing the rate at which D3 is converted to 25OHD.  There are numerous other causes of scatter as well, such as differences in absorption - but researchers have not yet characterised the various sources of scatter to a satisfactory degree.

I now regard RDA as the wrong approach to nutrition, at least for vitamin D.  Like many concepts whose initial attraction is their apparent simplicity - such as the BMI formula - the results are a mess because reality is complex and bad things happen when an unsubtle, inappropriate, overly-simple rule is applied which would only make sense if reality was much more constrained than it actually is.  The same thing would happen if it was assumed that multiple clothing sizes were silly and that what we really need is one size of shirts to fit everyone, or at least all adults, the world over - or even in one country.

An RDA calculation ignores 97.5% of the people.  It sets an intake for all people based solely on the 1/40th of the population with the lowest 25OHD levels.   There are numerous reasons for this variation - body weight is just the most obvious.

So I do not advocate pursuing the RDA for vitamin D.

The ratios I propose will not cause everyone to achieve 40ng/ml.   I think we should be happy with what it will achieve - double to four times the currently parlous 250HD levels of many people worldwide, with no risk of toxicity.

The Grassroots Health chart referred to above is produced by some of the world's foremost vitamin D researchers.   This states that for a population of people not taking D3 supplements other than multivitamins, who through UVB exposure, food and any multivitamins attain 25OHD levels of 20ng/ml, then D3 at 1.725 ug/kg bodyweight (69 IU/kg) per day 90% will attain at least 40ng/ml,   This is for a whole population, including an unspecified proportion of obese people.  Many of those who attain less than 40ng/ml will be obese. 

The experimental subjects of Ewaku et al. had an unspecified average unsupplemented 25OHD level, I guess in the order of 20ng/ml and my non-obese base ratio of 1.8 ug/kg bodyweight (72 IU/kg) per day should get more such people over 40ng/ml than the Grassroots Health ratio, partly because it specifies 4.3% more D3, but mainly because it applies to people who are not obese.  

The notes in the grey box above, below the ratios themselves, urges people whose unsupplemented 25OHD levels are likely to be lower than 20ng/ml to choose a ratio somewhat above the base ratio.   A particular concern is people with pigmented skin living far from the equator, especially in winter, especially if they cover their bodies whenever outside.  

Even in sunny Israel, at 32° north, we see that women who avoid sun exposure for cultural reasons (Arab - mainly Muslim - women, green on the bottom), frequently have disastrously low 25OHD levels.   Consider such women living in England, Scotland or Sweden - and their children.

Vitamin D blood levels in Israel for men and women of the main, Orthodox and Arab populations - adapted to show a healthy range of levels up to 60ng/ml.


© 2020 Robin Whittle   Daylesford, Victoria, Australia