Fat Soluble Vitamin D

By Cat, June 2007; Updated May 2019

It is difficult to talk about Vitamin D without also discussing Vitamin A, as they are so intricately linked, metabolically, and are both fat soluble. Unfortunately, combining them in one article made it too long, so Vitamin D now has its own article. Also the topics: Vitamin A:D Ratio for Optimum Intake, and the Cod Liver Oil Debate, are included in the Vitamin A article. Note that vitamins A and D work together, especially with the help of vitamin E.

Vitamin D was discovered as result of research on prevention of rickets (faulty mineralization of bones and teeth in children), and osteomalacia (progressive loss of calcium and phosphorus from the bones in adults). Although they knew that vitamin D is produced by the sun’s radiation on exposed skin, researchers tried to find food sources as well.

NOTE:  Consult with your health practitioner before taking any supplements.   Overuse of supplements, just as overuse of drugs, can lead to other health problems, and some supplements can interact negatively with other supplements or drugs.

Remember that the best way to get your vitamins, minerals and other nutrients is from fresh whole foods.

See Vitamins: Intro for

  • Introduction: Vitamins
  • Vitamin Supplementation vs Whole Foods

Vitamin D

Some history of Vitamin D

The first to be discovered, ergocalciferol, was termed D2. It is made by irradiating ergosterol produced by yeasts and fungi. This was followed by discovery of cholecalciferol, termed D3, which is present in animal tissues including human, and is quite abundant in certain fish like salmon, and cod liver oil.

D2 was cheaper to produce so was the dominant form added to pasteurized dairy products (pasteurization destroys milk’s natural vitamin D3) and other foods with reduced/depleted vitamin D content due to processing. But then it was discovered that not only was it NOT a very effective vitamin for humans, it could be toxic at doses above 400 IU/day. This lead to replacing D2 with D3 in processed foods and most supplements, because D3 is more effective and has a higher upper limit for safe dosing. However, D2 is still used in vegan supplement formulas.

Effect of vitamin D deficiency and toxicity

Once thought of as only playing a role in certain diseases (rickets, osteoporosis and increased risk of bone fracture), “researchers now realize that vitamin D affects virtually every cell and tissue in your body. And it affects numerous vitamin D receptors located throughout your body and nearly 3,000 genes.” (7I) A deficiency can also weaken our immune systems. See also Chemistry of Vitamin D section, below.

Your cells need the active form of vitamin D (to unlock the genetic blueprints stored inside the cell; without these, many aspects of your health would be at risk; here’s a sampling from the long list in Mercola’s article (7I):

  • Digestion and absorption of nutrients;
  • Heart and/or blood pressure health;
  • Neurological and cognitive health;
  • Muscular function;
  • Pancreatic function;
  • Carb and fat metabolism;
  • Hearing and vision.

Toxicity

Excessive exposure to sunlight does not lead to overproduction of vitamin D. Vitamin D toxicity is inevitably the result of overdosing on vitamin D supplements. (17C)

Symptoms of toxicity include weakness, loss of appetite, nausea, vomiting, diarrhea, excessive thirst, and weight loss. (12B) Another symptom is hardening of the arteries due to excessive calcification; this is a sign that you are deficient in Vitamin K2, which directs calcium to areas where it is needed, and keeps it away from areas  where it shouldn’t be, including your soft tissues and arteries. (7J)

Dietary Sources of Vitamin D

See also Worlds Healthiest Foods: Vitamin D (15A) for a great discussion of food sources of this vitamin, its forms (vitamins D2 and D3), its metabolism, function, supplemental dosage, etc.

Primary source:

You guessed it, “sunshine,” provides the best form of vitamin D. It doesn’t do so directly; rather its UVB rays interact with the cholesterol in your skin to make two forms of vitamin D3: cholecalciferol and cholecalciferol sulfate). The sulfated version is important since much of the body, including your blood stream, is watery fluid, so the sulfated version, which is water soluble, doesn’t need a carrier to transport it in the blood. On the other hand, the non-sulfated version is not water-solutble, so must be carried through the blood via LDL cholesterol. Plant and animal sources of D3 do not include the sulfate version. (7C)

It can be stored in the body until it is needed, so get lots of sunshine in the summer, allowing your body to store extra for the cloudy winter days. The best time to spend in the sun, to maximize the best rays, is mid-day, when the sun is at its apex.

Sunshine activates cholesterol in the skin to oil-soluble Vitamin-D and also water-soluble Vitamin-D Sulfate. The sulfated version is important since much of the body, including your blood stream, is watery fluid. The non-sulfated version must be carried through the blood via LDL cholesterol. Plant and animal sources of D3 (cholecalciferol) do not include the sulfate version. (7C)

D3 is a natural form of D3 (created by sunshine acting on cholesterol in your skin), but it is not the most active form; that would be 1,25-dihydroxycholecalciferol which is converted from D3 in 2 steps, the first in the liver and the second in the kidneys. (7C) See a Colorado State article on Vitamin D, for illustrations and discussion of conversion of D3 (from sunlight or a D3 supplement) to the more active forms. (17D)

An alternative to sunshine is a safe tanning bed. But since it’s hard to know if the bed is safe, sunshine is still your best bet – mid-day sun.

Food sources:

D3 is found in certain animal foods, such as raw milk, liver and cod liver oil. NOTE: pasteurizing milk destroys the D3, so a synthetic form, D2 (ergocalciferol) is usually added, though some dairies have changed to adding D3.

Raw Milk, especially from goats (15A): This is my favorite source; however, here in Montana, you have to get it from your own goat because purchasing it is illegal here (as of 2019).

Cod Liver Oil (CLO):  Traditional societies obtained vitamin D from the oils of fermented cod liver during winter months, but of course, they didn’t know it was vitamin D they were getting (along with essential fatty acids and vitamin A); they just knew it kept them healthy through the cold months.  In the early 1920s, the most recommended food to prevent rickets was fermented cod liver oil. (see also ncbi:  “Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective” (3K)).

Most other forms of cod liver oil (not from fermented livers) are very low in vitamin D because it is destroyed in the deodorizing process. Some brands add D3 back (along with vitamin A) after the processing is finished, but that may not be as active as the original vitamins.  

However, Green Pasture’s Blue Ice Fermented Cod Liver Oil (20A) is not deodorized and still retains all the original vitamins with an A:D ratio of 10:1. Or try the Fermented Cod Liver Oil and Butter Oil blend (20B) These products are available in capsules, or with added flavors, so you can avoid the awful flavor. I add the unflavored liquid form to my smoothie.

See also “The Cod Liver Oil Debate” in my Fat Soluble Vitamin A article.

Salmon and sardines (wild caught) (15A) These are high is Omega-e fats and also vitamin A.

Supplements:

Vitamin D supplements are available, but be sure to get the D3 version (cholecalciferol), not D2 (ergocalciferol), and recognize that such supplements are highly processed and may not be as effective as the vitamin in its native state.

D2 is a synthesized form of vitamin D, prepared by irradiating certain plant chemicals (derived from ergosterol in yeasts and fungi); it is much less effective than D3, and is toxic at low levels.

See also

  • Mercola: Why D supplementation is not the same as sunlight (7H), and may actually be immunorepressive by blocking VDR activation (Vitamin D Nuclear Receptor), opposite to the effect of vitamin D from sunshine
  • Science Daily, Jan 2008 (18): However it is not clear whether the D used in the study was D2 or D3; it speaks of D added to milk and cereals, which typically is D2.  It’s possible D3 would not produce the same immunorepressive effect as D2.

Role of vitamin D

Vitamin D is now recognized to be a hormone. From Hormone Health Network article on Vitamin D (21):

“Vitamin D is a hormone the kidneys produce that controls blood calcium concentration and impacts the immune system. It is also known as calcitriol, ergocalciferol, calcidiol and cholecalciferol. Of those, calcidiol is the form doctors most commonly focus on when measuring vitamin D levels in the blood.

The body makes vitamin D in a chemical reaction that occurs when sunlight hits the skin. This reaction produces cholecalciferol, and the liver converts it to calcidiol. The kidneys then convert the substance to calcitriol, which is the active form of the hormone in the body.

Vitamin D has its effects by binding to a protein (called the vitamin D receptor). This receptor is present in nearly every cell and affects many different body processes.”

In addition to the benefits sited below, more are sure to be discovered in the future.

Strong bones:

Vitamin D supports proper mineralization of bones. It stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood”.

See also Colorado State Univ on calcium (17B) regarding endocrine control of calcium homeostasis, in which vitamin D plays a crucial role.

Cancer and heart disease:

Vitamin D lowers risk of cancer & heart disease (and other cardio-vascular problems), and supports many body functions in it’s hormonal role. It plays a crucial role in cancer development, through its protective mechanisms (from Mercola on UK study (7D)):

  • Regulating genetic expression;
  • Increasing the self-destruction of mutated cells (so they don’t replicate & become cancerous);
  • Reducing spread and reproduction of cancer cells;
  • Causing cells to become differentiated (cancer cells often lack differentiation);
  • Reducing growth of new blood vessels from pre-existing ones, thus preventing transition of tumors from dormant to malignant.

However, the minimum dose to prevent cancer has been raised to 60 ng/ml (nanograms per milliliter) – exactly three times the amount of 20 ng/mL recommended in 2010 by the National Academy of Medicine (16).  Twenty minutes of direct sunlight three times a week is recommended as a starting point.; also add dietary sources such as pasture-raised local eggs from farmers you trust, cold-water fatty fish (like wild salmon), Organic mushrooms, and raw dairy. (Don’t forget: always seek the highest quality food possible, to avoid toxins). But to get the 60 ng/ml level, you may want to add supplemental vitamin D3.

See also

  • Mercola: Papers from a Canadian conference on vitamin D (4E)
  • Cancer Prevention (links to my old iWEb site, Disease section) for exciting research on Vitamin D and cancer.

Depression:

Mercola article: New Study Shows Vitamin D Helps Prevent Depression (7F) (see study: Vitamin D intake from foods and supplements and depressive symptoms in a diverse population of older women. (3I)):

  • depression and low levels of vitamin D may be linked
  • Best way to get vitamin D is from the sun. This is because the sun activates the formation of vitamin D sulfate, which is water soluble (other forms of D are not water soluble and must be transported by LDL cholesterol). Water soluble vitamin D has a far better chance of getting through the body fluids and into the cells.

Immunity:

There is a relationship between vitamin-D deficiency (especially in winter) with influenza (flu). My notes from a Mercola article (7G) on this topic:

Scientists hypothesize that influenza is actually a vitamin-D deficiency disease, which is exacerbated in the winter, when there is significantly reduced available sunshine.  This hypothesis was presented by Dr. John Cannell and colleagues in the journal Epidemiology and Infection (3J) in 2006, and again, more recently, in the Virology Journal (19)

Vitamin D (formed in the skin when exposed to sunshine) regulates expression of over 2000 genes throughout the body, including those responsible for immune response to various bacteria and viruses.  Thus this theory could account for any number of viral diseases typically occurring in winter, such as colds and flu.

Testing for Your Vitamin D Levels

It’s important to have your vitamin D levels tested periodically. Optimal blood level of vitamin D is determined by a simple blood test that your doctor can order. Do not use the “1,25(OH)D” test (as from Quest Labs) as it is not as good a marker of overall D status. Go for the “25(OH)D,” also called 25-hydroxyvitamin D or 25-OHD, such as from Lab Corp. (7B)

Thenormal lab range” for 25-hydroxyvitamin D (25-OHD) is between 20-56 ng/ml, but this conventional range is really a sign of deficiency, and is too broad to be ideal, according to Dr. Mercola. He states that any levels below 20 ng/ml are considered serious deficiency states, increasing your risk of as many as 16 different cancers and autoimmune diseases like multiple sclerosis and rheumatoid arthritis, just to name a few. (7B)

25-OHD level guidelines, according to Mercola(7B,7C):*

  • OPTIMAL level for everyone, no matter age, is 50-65 ng/ml;
  • Serious deficiency: < 20 ng/ml,
  • Deficiency: < 50 ng/ml
  • Optimal: 50 – 70 ng/ml
  • To treat cancer and heart disease: 70 – 100 ng/ml
  • Excess: > 100 ng/ml

‘*NOTE: these are blood levels of the metabolite 25-OHD, not dietary D3 intake amounts.

Chemistry of Vitamin D

As mentioned above, while D3 is a natural form of vitamin D, it is not the most active form; that would be 1,25-dihydroxycholecalciferol which is converted from D3 in 2 steps: (17D)

  1. Within the liver, cholecalciferal [D3] is hydroxylated to 25-hydroxycholecalciferol [abbreviated as 1,25(OH)D] by the enzyme 25-hydroxylase.
  2. Within the kidney, 25-hydroxycholecalciferol serves as a substrate for 1-alpha-hydroxylase, yielding 1,25-dihydroxycholecalciferol, the biologically active form [25(OH)D].

This active form of vitamin D (25(OH)D) binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones (17C), the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription.

The vitamin D receptor binds several forms of cholecalciferol. Its affinity for 1,25(OH)D is roughly 1000 times that for 25(OH)D, which explains their relative biological potencies.

See Colorado State on vitamin D (17A) for great text and reaction drawings.

Vitamins A:D Ratio

It’s definitely a matter of balance between vitamins A and D, as each cannot properly function without the other, and each provides protection from the toxicity of the other. However, too much of either one can result in trouble.

Is there an optimum ratio of vitamins A and D? Yes, but the experts cannot seem to agree. For more, see Vitamin A:D Ratio for Optimum Intake, and Cod Liver Oil Debate, included in my Fat Soluble Vitamin A article.

References

References 1 – 6 are common to all my vitamin pages; those specific with vitamins A and D begin with number 7.

  1. well.blogs.nytimes.com/2008/02/06/despite-risks-vitamins-popular-with-cancer-patients/
  2. (6) dailyyonder.com/four-food-groups/2010/03/04/2623
  3. ncbi abstracts (3B – 3G originally cited in Supplements for Insulin Resistance, as numbers 21A – 21F)
    1. (new) ncbi.nlm.nih.gov/pubmed/23183291
    2. (21A in Supplements for IR) ncbi.nlm.nih.gov/pubmed/7622343
    3. (21B) ncbi.nlm.nih.gov/pubmed/6278902
    4. (21C) ncbi.nlm.nih.gov/pubmed/22986984
    5. (21D) ncbi.nlm.nih.gov/pubmed/9169302
    6. (21E) ncbi.nlm.nih.gov/pubmed/3017301
    7. (21F) ncbi.nlm.nih.gov/pubmed/8131066
    8. (9A) ncbi.nlm.nih.gov/pubmed/19091068 for Nutrition Journal, December 17, 2008 on PubMed
    9. (D9) ncbi.nlm.nih.gov/pubmed/21865327
    10. (D11) ncbi.nlm.nih.gov/pmc/articles/PMC2870528/
    11. (D13) ncbi.nlm.nih.gov/pubmed/12897318
  4. Selene River Press, by and about Dr Royal Lee, regarding Dr W. A. Price’s XFactor:
    1. Dr Royal Lee’s original article on Dr Weston A. Price’s XFactor: seleneriverpress.com/historical/dr-royal-lee-on-the-x-factor-of-dr-weston-a-price/; or see the original article: 6sd6hj41ya-flywheel.netdna-ssl.com/images/pdfs/40_weston_price_vitamin_f.pdf (I’ve also saved it as a pdf: CATSFORK > PDF FILES / Price-VitaminF-XFactor_Dr RoyalLee.pdf)
    2. Butter, Vitamin E, and the X-Factor (historical archive of Dr Lee’s article) (seleneriverpress.com/historical/butter-vitamin-e-and-the-x-factor-of-weston-a-price/)
    3. Lectures of Dr. Royal Lee, Vitamin News (seleneriverpress.com/shop/lectures-of-dr-royal-lee-volume-i-pdf-ebook/
    4. Vitamin News, a collection of all the biannual issues in one book: (seleneriverpress.com/shop/vitamin-news/
    5. SRP Historical Archives:  seleneriverpress.com/srp-historical-archives/
  5. Articles on The X-Factor of Dr. Weston A. Price:
    1. (5) realmilk.com/health/x-factor-vitamin-k2/
    2. (6) blog.radiantlifecatalog.com/bid/59999/The-Mystery-of-X-Factor-Butter-Oil-and-Vitamin-K2-Solved
  6. More articles by Dr. Royal Lee: soilandhealth.org/wp-content/uploads/02/0203CAT/royal.lee.lets.live.articles.htm
  7. Mercola: differences from vitamin b list begins here
    1. (A7) articles.mercola.com/sites/articles/archive/2008/12/23/important-cod-liver-oil-update.aspx
    2. (D1) articles.mercola.com/sites/articles/archive/2008/12/27/important-vitamin-d-update.aspx
    3. (D2) articles.mercola.com/sites/articles/archive/2011/12/14/study-shows-vitamin-d-cuts-flu-by-nearly-50.aspx?e_cid=20111209_DNL_artTest_C5
    4. (D6) articles.mercola.com/sites/articles/archive/2011/12/19/why-are-cancer-cases-rising-by-nearly-50-in-the-next-20-years.aspx
    5. (D7) articles.mercola.com/sites/articles/archive/2009/12/01/Important-New-Vitamin-D-Research-Papers.aspx
    6. (D8) articles.mercola.com/sites/articles/archive/2011/11/13/vitamin-d-for-depression.aspx
    7. (D10) articles.mercola.com/sites/articles/archive/2008/11/18/do-flu-shots-work-ask-a-vaccine-manufacturer.aspx
    8. (D15) articles.mercola.com/sites/articles/archive/2008/02/12/why-vitamin-d-supplements-are-not-the-same-as-sunlight.aspx
    9. (new) products.mercola.com/vitamin-d-supplement/
    10. (new) .mercola.com/article/vitamin-d-resources.htm
  8. Weston A Price:
    1. (A5, AD3) westonaprice.org/The-Cod-Liver-Oil-Debate.html
    2. (A6, AD1) westonaprice.org/A-Response-to-Dr.-Joe-Mercola-on-Cod-Liver-Oil.html
    3. (AD2) westonaprice.org/Cod-Liver-Oil-Basics-and-Recommendations.html
    4. (new) westonaprice.org/health-topics/cod-liver-oil/report-cod-liver-oil/
  9. Wikipedia:
    1. (A4) wikipedia.org/wiki/Vitamin_A
  10. (A1) The Nature of Vitamin A in Cod Liver Oil: jbc.org/cgi/reprint/125/2/475.pdf
  11. (A2) Oregon State Univ:
    1. lpi.oregonstate.edu/infocenter/vitamins/vitaminA/
    2. lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/carotenoids
  12. Cyber North
    1. (A3) cyber-north.com/vitamins/vitamina.html
    2. (D4)ccyber-north.com/vitamins/vitamind.html
  13. (A8) weightlossresources.co.uk/nutrition/vitamins/vitamin_a.htm
  14. brightfocus.org/macular/article/vitamins-age-related-macular-do-you-have-correct-formula
  15. World’s Healthiest Foods:
    1. (D3) whfoods.org/genpage.php?tname=nutrient&dbid=110
  16. (D17) naturalhealth365.com/vitamin-d-levels-cancer-2617.html
  17. Colorado State:
    1. (D12) vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/vitamind.html
    2. (D5) vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/calcium.html
    3. (new) vivo.colostate.edu/hbooks/pathphys/endocrine/moaction/intracell.html
  18. (D16) sciencedaily.com/releases/2008/01/080125223302.htm
  19. Virology Journal, John J. Cannell ,et. al., On the epidemiology of influenza:
    virologyj.biomedcentral.com/articles/10.1186/1743-422X-5-29
  20. (replacesD14; Dr Ron’s no longer carries these) Green Pastures:
    1. Fermented cod liver oil: greenpasture.org/public/products/fermentedcodliveroil/, also available on Amazon (ASIN B002LZYPS0);
    2. Fermented cod liver oil and concentrated butter oil: greenpasture.org/public/products/fermentedcodliveroilconcentratedbutteroilblend/, also available on Amazon (ASIN B00OZHWX1I)
  21. Hormone Health Network: Vitamin D (hormone.org/hormones-and-health/hormones/vitamin-d)

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