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How does vitamin A deficiency arise?

How does vitamin A deficiency arise?



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How does vitamin A deficiency arise?

I am living in a "developed" country, so excuse me if I miss some facts that are real, and threatening, in other parts of our world.

I heard about https://en.wikipedia.org/wiki/Vitamin_A_deficiency , but looking at what foodstuff contains vitamin A or precursors, I'm at loss how anyone can suffer from vitamin A deficiency.

Obviously, I'm lacking some information here.

One thing that looks particularly misleading is when you are presented with vitamin A contents of foods, neglecting precursors like carotenoids that can be easily converted to vitamin A as needed.

As a (sometimes misleading) rule of thumb, I was thinking that most yellow or orange looking food was prone to contain vitamin A or some of its precursors.


The WHO report "Global prevalence of vitamin A deficiency in populations at risk 1995-2005" (page 12 of 68) puts it like this:

Where animal source or fortified foods are minimally consumed, dietary adequacy must rely heavily on foods providing beta-carotene. However, while nutritious in many ways, a diet with modest amounts of vegetables and fruits as the sole source of vitamin A may not deliver adequate amounts, based on an intestinal carotenoid-to-retinol conversion ratio of 12:1 (2) This ratio reflects a conversion efficiency that is about half that previously thought, leading to greater appreciation for why VAD may coexist in cultures that heavily depend on vegetables and fruits as their sole or main dietary source of vitamin A.

Usually, VAD develops in an environment of ecological, social and economical deprivation, in which a chronically deficient dietary intake of vitamin A coexists with severe infections, such as measles, and frequent infections causing diarrhoea and respiratory diseases that can lower intake through depressed appetite and absorption, and deplete body stores of vitamin A through excessive metabolism and excretion (3, 4). The consequent “synergism” can result in the body's liver stores becoming depleted and peripheral tissue and serum retinol concentrations decreasing to deficient levels, raising the risks of xerophthalmia, further infection, other VADD and mortality.

Just as a side note: green leaves contain heaps of beta-carotenes as well!


Vitamin A Deficiency

Image courtesy of the Nutrition Program via the Public Health Image Library of the Centers for Disease Control and Prevention.

Vitamin A is required for the formation of rhodopsin, a photoreceptor pigment in the retina (see table Sources, Functions, and Effects of Vitamins). Vitamin A helps maintain epithelial tissues and is important for lysosome stability and glycoprotein synthesis.

Dietary sources of preformed vitamin A include fish liver oils, liver, egg yolks, butter, and vitamin A–fortified dairy products. Beta-carotene and other provitamin carotenoids, contained in green leafy and yellow vegetables, carrots, and deep- or bright-colored fruits, are converted to vitamin A . Carotenoids are absorbed better from vegetables when they are cooked or homogenized and served with some fat (eg, oils). Normally, the liver stores 80 to 90% of the body’s vitamin A . To use vitamin A , the body releases it into the circulation bound to prealbumin (transthyretin) and retinol-binding protein.

Retinol activity equivalents (RAE) were developed because provitamin A carotenoids have less vitamin A activity than preformed vitamin A 1 mcg retinol = 3.33 units.

Synthetic vitamin analogs (retinoids) are being used increasingly in dermatology. The possible protective role of beta-carotene, retinol, and retinoids against some epithelial cancers is under study. However, risk of certain cancers may be increased after beta-carotene supplementation.


How does vitamin A deficiency arise? - Biology

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Vitamin C deficiency

Severe ascorbic acid deficiency has been known for centuries in the form of a potentially fatal disease such as scurvy.

Symptoms of scurvy include subcutaneous bleeding, poor wound healing and easy bruising, loss of hair and teeth, as well as the pain and swelling in the joints.

These symptoms seem to be related to the weakening of blood vessels, connective tissue and bone, all of which contain collagen.

Scurvy early symptom, such as fatigue, may result from reduced levels of carnitine, which is required to obtain energy from fat, or due to decreased synthesis of catecholamines - norepinephrine.


3. Anemia

During pregnancy, a woman’s requirement of vitamin A, both for herself and her growing baby, increases considerably. Healthy mothers consuming a nutrient-rich diet normally have a sufficient store of vitamin A in the liver. 23 However, studies show that women with insufficient dietary intake of vitamin A during pregnancy – a common feature among impoverished communities in developing countries – suffer from anemia or low numbers of healthy red blood cells and night blindness. Their susceptibility to VAD is higher in the third trimester of pregnancy when fetal growth and the mother’s own blood volume increases.

Anemia can have serious consequences if left untreated:

  • Risk of membrane rupture in the uterus
  • Premature delivery
  • Stillbirth
  • Death of the mother

As a result of anemia from vitamin A deficiency during pregnancy, a baby is also seriously impacted in several ways:

  • Risk of death in the baby’s first year of life
  • Low birth weight/small size
  • Low levels of hemoglobin

Vitamin A supplements taken during pregnancy under medical supervision can help decrease the frequency of anemia. 24 Other studies claim that vitamin A supplements prescribed as late as the second and third trimester do not hold out the promise of improving the mother’s health or that of her baby. A balanced diet with sufficient nutrients is the best way to avoid anemia during pregnancy. 25


Vitamin C

Which Vitamins Are Good for Muscle Pains?

Vitamin C, also called ascorbic acid, is a vitamin that is important in the production of collagen, a key component in tendons, ligaments and bones -- which all have an impact on your joints. A deficiency in vitamin C can cause weakening in the connective tissues that form your joints, leading to joint pain and swelling. For healthy joints, an average adult male needs an intake of 90 milligrams of vitamin C daily, while a female needs 75 milligrams. Load up of veggies and fruits, especially strawberries and red peppers, to fight vitamin C deficiency.

  • Vitamin C, also called ascorbic acid, is a vitamin that is important in the production of collagen, a key component in tendons, ligaments and bones -- which all have an impact on your joints.

How does vitamin A deficiency arise? - Biology

All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited.

Feature Papers represent the most advanced research with significant potential for high impact in the field. Feature Papers are submitted upon individual invitation or recommendation by the scientific editors and undergo peer review prior to publication.

The Feature Paper can be either an original research article, a substantial novel research study that often involves several techniques or approaches, or a comprehensive review paper with concise and precise updates on the latest progress in the field that systematically reviews the most exciting advances in scientific literature. This type of paper provides an outlook on future directions of research or possible applications.

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to authors, or important in this field. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.


New Study: Vitamin D reduces risk of ICU admission 97%

This is a peer-reviewed, randomized, controlled study of hospitalized Covid-19 patients. So it is an “RCT”. [Correction: no placebo was used. The intervention group received calcifediol and the control group did not. Both groups received BAT, best available treatment.] This is the type of study that the press and various online critics demand. Some persons unwisely reject all other types of studies, which is not reasonable or scientific. But this is the type of study we’ve been waiting for, to confirm the other 20 studies here.

The study took place in a university hospital setting: Reina Sofia University Hospital, in Cordoba, Spain. The 76 patients were all hospitalized for confirmed cases of Covid-19. So these are not the mild to moderate, stay-at-home types of patients. The intervention group was 50 patients and the control group was 26 patients.

The intervention group received calcifediol, which is a type of vitamin D found in the blood. It is not the usual type of vitamin D found in supplements. Calcifediol is also known as 25(OH)D or 25-hydroxyvitamin D. The reason for giving this type of vitamin D is that the usual supplement type takes about 7 days to turn into calcifediol, so by giving patients calcifediol itself, you get the good effects without having to wait 7 or so days [per Wikipedia].

The dosage of calcifediol converts to IU (international units at a ratio of 200 to 1). So 10 micrograms of calcifediol is 2000 IU of vitamin D, whereas 10 micrograms of vitamin D3 is 400 IU (a 40:1 ratio). The dosage given to the patients, in IUs, was:

Day one: 106,400 IU of vitamin D
Day three: 53,200 IU
Day seven: 53,200 IU
Once-a-week thereafter: 53,200 IU

Yes, you can take your vitamin D supplement in a once-a-week dosage, instead of daily.

The results were astounding (and highly statistically significant). “Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%)”. Would you rather have a 50% risk of needing ICU care, or a 2% risk? Almost all hospitalized Covid-19 patients who die, die in the ICU. That is where the most severe cases are sent. So this study shows that vitamin D reduces the severity of Covid-19.

In the statistically adjusted results, vitamin D reduced the odds of ICU admission by 97%. The RR (risk reduction) for ICU admission in hospitalized Covid-19 patients was 0.03 as compared to the control, which is given the value of 1.00. The odds of Covid-19 patients in general, as compared to hospitalized Covid-19 patients, needing ICU care would be even lower, as you would first need to be hospitalized to enter that risk ratio, and vitamin D has been shown by other studies to reduce risk of hospitalization. So taking a vitamin D supplement has tremendous benefits.

For mortality, 2 patients in the control group died no patients in the vitamin D group died. There were not enough deaths to make the results statistically significant. But hospitalized patients don’t usually die from Covid-19, unless they are in the ICU. We would expect the reduction in death to be of a similar order of magnitude to the reduction in need for ICU care. Also, if you need mechanical ventilation, that is ICU care. So the vitamin D would seem to reduce risk of ventilation as well.

There is now enough evidence for treatment with calcifediol, also known as 25(OH)D, to be STANDARD CARE for hospitalized patients with Covid-19. There is enough evidence for vitamin D supplementation to be recommended to everyone at risk of vitamin D, especially those at high risk. And since the elderly often have difficulty absorbing vitamin D, they should receive a higher dosage.

Here’s a video on the study by Dr. Mobeen Syed (of DrBeen’s Medical Lectures)

There are over 40 studies on Vitamin D and Covid-19, each showing a substantial benefit by reduction of risk: lower risk of contracting Covid-19, lower risk of having a severe case, lower risk of needing hospital admission or ICU admission or mechanical ventilation, and many showing lower risk of death from Covid-19. There is no other over-the-counter or prescription medication or supplement that has so many studies showing such a large benefit. And the risk of taking vitamin D, an essential nutrient, are very low, essentially nil.

The medication in this study is the form of vitamin D that your body makes out of ordinary over-the-counter Vitamin D3, after it is processed by the liver. Almost all other studies used Vitamin D3 itself, with the many benefits discussed above. How much Vitamin D3 should you take?

If you have Covid-19, take 100,000 IU of vitamin D3 every day for 5 days. Then take either 10,000 IU of vitamin D3 daily OR 100,000 IU of vitamin D3 once a week (rather than daily). If you do not have Covid-19, just take the daily dose of 10,000 IU of vitamin D3 OR the weekly dose of 100,000 IU of vitamin D3.

If every hospitalized Covid-19 patient were given calcifediol, the reduction in need for ICU beds and mechanical ventilation would be anticipated to be large. And since Covid-19 patients, if they are going to die from the disease, usually die in ICU, this should reduce deaths by at least half as well.

Having normal healthy blood levels of vitamin D reduces Covid-19 risks, including risk of infection [7, 8, 9, 11, 12, 14, 16, 23, 27, 32, 33, 37, 41], of having a severe case [1, 3, 4, 5, 15, 17, 20, 22, 24, 25, 26, 30, 34, 39, 40, 42, 43, 44, 45], of needing hospitalization, ICU care, and/or mechanical ventilation [2, 10, 14, 15, 21, 22, 24, 26, 30, 35, 40, 44], as well as the risk of dying from Covid-19 [4, 6, 7, 9, 12, 13, 17, 18, 19, 22, 24, 25, 31, 34, 36, 38, 40, 45, 46, 47, 48].

Ronald L. Conte Jr.
Covid.us.org
Follow Covid.us.org on Twitter
Note: The author of this article is not a doctor, nurse, or healthcare provider.

Vitamin D versus Covid-19, Studies

1. Alipio, Mark. “Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19).” SSRN 3571484 (9 April 2020).
Study Link | PDF Link

2. Lau, Frank H., et al. “Vitamin D insufficiency is prevalent in severe COVID-19.” medRxiv (28 April 2020).
Study Link | PDF Link

3. Daneshkhah, Ali, et al. “The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients.” medRxiv (2020).
Study Link | PDF Link

4. Davies, Gareth, Attila R. Garami, and Joanna C. Byers. “Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes.” medRxiv (2020).
Study Link | PDF Link

5. De Smet, Dieter, et al. “Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics.” medRxiv (2020).
Study Link | PDF Link

6. Raharusun, Prabowo, et al. “Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study.” (2020).
PDF file | PDF Link

7. Ilie, Petre Cristian, Simina Stefanescu, and Lee Smith. “The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality.” Aging Clinical and Experimental Research (2020): 1.
Study Link | PDF Link

8. D’Avolio, Antonio, et al. “25-hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2.” Nutrients 12.5 (2020): 1359.
Study Link | PDF Link

9. Laird, E., et al. “Vitamin D and Inflammation: Potential Implications for Severity of Covid-19.” Ir Med J Vol 113 No. 5 P81: 2020.
PDF file | PDF Link

10. Faul, J.L., et al. “Vitamin D Deficiency and ARDS after SARS-CoV-2 Infection.” Ir Med J Vol 113 No. 5 P84: 2020.
PDF file | PDF Link

11. Meltzer, David O., et al. “Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence.” medRxiv (2020).
Study Link | PDF Link

12. Li, Yajia, et al. “Sunlight and vitamin D in the prevention of coronavirus disease (COVID-19) infection and mortality in the United States.” (2020).
PDF file | PDF Link

13. Pugach, Isaac Z. and Pugach, Sofya “Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe.” medRxiv (2020).
Study Link | PDF Link

14. Merzon, Eugene, et al. “Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study.” medRxiv (2020). — Low vitamin D increased risk (adjusted OR) of infection with Covid-19 by 45% and of hospitalization for Covid by 95%.
Study Link | PDF Link

15. Panagiotou, Grigorios et al., “Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.” medRxiv (2020). Conclusion: “we found that patients requiring ITU admission [in the ICU] were more frequently vitamin D deficient than those managed on medical wards [on the floor], despite being significantly younger.”
PDF file Link | PDF Link

16. Chang, Timothy S., et al. “Prior diagnoses and medications as risk factors for COVID-19 in a Los Angeles Health System.” medRxiv (2020).
Study Link | PDF Link

Risk factors included vitamin D deficiency, which increased risk of COVID-19 diagnosis by 80% (OR 1.8 [1.4-2.2], p=5.7 x 10-6).

17. Maghbooli, Zhila, et al. “Vitamin D Sufficiency Reduced Risk for Morbidity and Mortality in COVID-19 Patients.” Available at SSRN 3616008 (2020).
Study Link | PDF Link

Vitamin D sufficiency reduced clinical severity and inpatient mortality.
* See this Expression of Concern by the editors of PLoS One

18. Panarese and Shahini, “Letter: Covid-19 and Vitamin D” Alimentary Pharmacology and Therapeutics, April 12, 2020.
Link to Letter | PDF Link

Covid-19 mortality increases with increasing latitude (by nation), and vitamin D blood levels decrease with increasing latitude. The authors propose that low levels of vitamin D increase Covid-19 mortality.

19. Carpagnano, Giovanna Elisiana, et al. “Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19.” Journal of Endocrinological Investigation (2020): 1-7. Study Link | PDF Link

“A survival analysis highlighted that, after 10 days of hospitalization, severe vitamin D deficiency patients had a 50% mortality probability, while those with vitamin D = 10 ng/mL had a 5% mortality risk (p = 0.019).”

20. Mardani, R., et al. “Association of vitamin D with the modulation of the disease severity in COVID-19.” Virus Research (2020): 198148. Study Link | PDF Link

21. Castillo, Marta Entrenas, et al. “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.” The Journal of Steroid Biochemistry and Molecular Biology (2020): 105751. Study Link | PDF Link

22. Radujkovic, et al. “Vitamin D Deficiency and Outcome of COVID-19 Patients.” Nutrients 2020, 12(9), 2757 Study Link | PDF Link
— “The present study demonstrates an association between VitD deficiency and severity of COVID-19.
VitD-deficient patients had a higher hospitalization rate and required more (intensive) oxygen therapy
and IMV. In our patients, when adjusted for age, gender, and comorbidities, VitD deficiency was
associated with a 6-fold higher hazard of severe course of disease and a

15-fold higher risk of death.”

23. Israel, Ariel, et al. “The link between vitamin D deficiency and Covid-19 in a large population.” MedRxiv 9/7/2020. Study Link | PDF Link

24. Jae Hyoung Im, et al. “Nutritional status of patients with coronavirus disease 2019 (COVID-19).”
International Journal of Infectious Diseases. August 7, 2020. PDF Link | PDF Link

25. Gennari L, et al “Vitamin D deficiency is independently associated with COVID-19 severity and mortality” ASBMR 2020 Abstract 1023. Study Link | PDF Link

26. Baktash, Vadir, et al. “Vitamin D status and outcomes for hospitalised older patients with COVID-19.” Postgraduate Medical Journal (2020). Study Link | PDF Link
— “The main findings of our study suggest that older patients with lower serum concentrations of 25(OH)D, when compared with aged-matched vitamin D-replete patients, may demonstrate worse outcomes from COVID-19. Markers of cytokine release syndrome were raised in these patients and they were more likely to become hypoxic and require ventilatory support in HDU.” [HDU is high dependency unit]

27. Kaufman HW, et al. “SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels.” (2020) PLoS ONE 15(9): e0239252. Study Link | PDF Link
— Optimum vitamin D blood level for reducing Covid-19 infection was found to be in the 50’s (ng/ml). This is the first study to show that 25(OH)D at levels above 30 have additional benefits.

28. Brenner, Hermann, Bernd Holleczek, and Ben Schöttker. “Vitamin D Insufficiency and Deficiency and Mortality from Respiratory Diseases in a Cohort of Older Adults: Potential for Limiting the Death Toll during and beyond the COVID-19 Pandemic?.” Nutrients 12.8 (2020): 2488. PDF Link
— “Compared to those with sufficient vitamin D status, participants with vitamin D insufficiency and deficiency had strongly increased respiratory mortality, with adjusted hazard ratios (95% confidence intervals) of 2.1 (1.3-3.2) and 3.0 (1.8-5.2) overall, 4.3 (1.3-14.4) and 8.5 (2.4-30.1) among women, and 1.9 (1.1-3.2) and 2.3 (1.1-4.4) among men. Overall, 41% (95% confidence interval: 20-58%) of respiratory disease mortality was statistically attributable to vitamin D insufficiency or deficiency. Vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D3 supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women.”

29. Pepkowitz, Samuel H., et al. “Vitamin D Deficiency is Associated with Increased COVID-19 Severity: Prospective Screening of At-Risk Groups is Medically Indicated.” (2020). PDF File
— Persons hospitalized for Covid-19 were more than twice as likely to need ICU care if they had with vitamin D deficiency.

30. Mandal, Amit KJ, et al. “Vitamin D status may indeed be a prognosticator for morbidity and mortality in patients with COVID‐19.” Journal of Medical Virology. PDF Link
— Findings: “patients with low concentrations of 25OH-D (<or=30nmol/l) demonstrated clinically relevant, elevated markers of cytokine release syndrome and were more likely to become hypoxic and require ventilatory support."

31. Karahan and Katkat. “Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients with COVID-19 in Turkey.” The journal of nutrition, health & aging (2020). PDF File

32. Faniyi, et al. “Vitamin D status and seroconversion for COVID-19 in UK healthcare workers who isolated for COVID-19 like symptoms during the 2020 pandemic.” medRxiv 6 Oct. 2020. PDF Link
— “Vitamin D deficiency is a risk factor for COVID-19 seroconversion for NHS healthcare workers especially in BAME male staff.”

33. Yılmaz, Kamil, and Velat Şen. “Is Vitamin D Deficiency a Risk Factor for Covid 19 in Children?.” Pediatric Pulmonology. Study Link
— “The symptom of fever was significantly higher in COVID‐ 19 patients who had deficient and insufficient vitamin D levels than in patients who had sufficient vitamin D level.”
— “Patients with COVID‐19 had significantly lower vitamin D levels 13.14 ng/ml than did the controls 34.81 ng/ml.”

34. Annweiler, C. et al. “Vitamin D and survival in COVID-19 patients: A quasi-experimental study.” The Journal of Steroid Biochemistry and Molecular Biology, 13 October 2020. Study Link
— Bolus vitamin D3 supplementation during or just before COVID-19 was associated with less severe COVID-19 and better survival rate in frail elderly.

35. Han, Jenny E., et al. “High dose vitamin D administration in ventilated intensive care unit patients: a pilot double blind randomized controlled trial.” Journal of clinical & translational endocrinology 4 (2016): 59-65. Study Link
— Hospital stay cut in half for patients needing ICU care and ventilation and receiving 100,000 IU Vitamin D3 daily for 5 days. Note that this was not a Covid-19 specific study, but a study of ICU patients on mechanical ventilation.

36. De Smet, Dieter, et al. “Serum 25 (OH) D Level on Hospital Admission Associated With COVID-19 Stage and Mortality.” American journal of clinical pathology (2020). Study Link
— Covid-19 patients admitted to hospital were 3.87 times more likely to die from Covid-19, if they had vitamin D deficiency.

37. Rastogi, Ashu, et al. “Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study).” Postgraduate medical journal (2020). Study Link
— Covid-19 patients were given 60,000 IU vitamin D daily for 7 days these patients were 3.0 times more likely to become negative for Covid-19 than patients not given vitamin D.

38. Afshar, Parviz, Mohammad Ghaffaripour, and Hamid Sajjadi. “Suggested role of Vitamin D supplementation in COVID-19 severity.” Journal of Contemporary Medical Sciences 6.4 (2020). Study Link
— 300,000 IU vitamin D3 once, then 100 IU per kilogram of body weight per day greatly reduced deaths and length of hospital stay for Covid-19.

39. Luo, Xia, et al. “Vitamin D Deficiency Is Inversely Associated with COVID-19 Incidence and Disease Severity in Chinese People.” The Journal of Nutrition (2020). Study Link
— vitamin D deficiency (<30 nmol/L) (OR: 2.72) was significantly associated with COVID-19 severity.

40. Pereira, Marcos, et al. “Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis.” Critical reviews in food science and nutrition (2020): 1-9. Study Link
— severe cases of COVID-19 present 64% more vitamin D deficiency compared with mild cases. A vitamin D concentration insufficiency increased hospitalization and mortality from COVID-19. We observed a positive association between vitamin D deficiency and the severity of the disease.

41. Katz, Joseph, Sijia Yue, and Wei Xue. “Increased risk for Covid-19 in patients with Vitamin D deficiency.” Nutrition (2020): 111106. Study Link
— “patients with vitamin D deficiency were 5 times more likely to be infected with Covid-19 than patients with no deficiency after adjusting for age groups”

42. Arvinte, Cristian, Maharaj Singh, and Paul E. Marik. “Serum Levels of Vitamin C and Vitamin D in a Cohort of Critically Ill COVID-19 Patients of a North American Community Hospital Intensive Care Unit in May 2020: A Pilot Study.” Medicine in drug discovery 8 (2020): 100064. Study Link
— “Serum levels of vitamin C and vitamin D were low in most of our critically ill COVID-19 ICU patients.”

43. Yılmaz, Kamil, and Velat Şen. “Is vitamin D deficiency a risk factor for COVID‐19 in children?.” Pediatric Pulmonology 55.12 (2020): 3595-3601. Study Link | Explanation of Study
— Children in this study with higher vitamin D blood levels (20 ng/ml or higher) were 4.6 times more likely to have no symptoms while infected with Covid-19, and 72% less likely to have a moderate/severe case of Covid-19 than children with vitamin D deficiency.

44. Tan, Chuen Wen, et al. “A cohort study to evaluate the effect of combination Vitamin D, Magnesium and Vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients.” medRxiv (2020). Study Link
— “a vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both.”

45. Jain, Anshul, et al. “Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers.” Scientific reports 10.1 (2020): 1-8. Study Link
— “The fatality rate was high in vitamin D deficient (21% vs 3.1%). Vitamin D level is markedly low in severe COVID-19 patients.” In this study, patients with low vitamin D had a mortality rate of 21% those with higher vitamin D had a mortality rate of only 3.1%. Those with higher vitamin D were more likely to have a mild case, and less likely to die those with low vitamin D were more likely to have a severe case, and more likely to die.

46. Ling, Stephanie F., et al. “High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study.” Nutrients 12.12 (2020): 3799. Study Link
— “In this observational study, treatment with cholecalciferol booster therapy, regardless of baseline serum 25(OH)D levels, appears to be associated with a reduced risk of mortality in acute in-patients admitted with COVID-19.” In one group, the reduction in risk of death was 87% in the other group, the reduction was 62%.

The evidence is overwhelming. Persons with Covid-19 should be given high-doses of Vitamin D3 (called “Cholecalciferol”) to reduce risk of death. Many other studies (above) showed similar results.

47. Vassiliou, Alice G., et al. “Low 25-Hydroxyvitamin D Levels on Admission to the Intensive Care Unit May Predispose COVID-19 Pneumonia Patients to a Higher 28-Day Mortality Risk: A Pilot Study on a Greek ICU Cohort.” Nutrients 12.12 (2020): 3773. Study Link
— “All patients who died within 28 days belonged to the low vitamin D group…. Critically ill COVID-19 patients who died in the ICU within 28 days appeared to have lower ICU admission 25(OH)D levels compared to survivors.”

48. Anjum, S., et al. “Examine the association between severe Vitamin D deficiency and mortality in patients with Covid-19.” Pakistan Journal of Medical and Health Sciences (2020): 1184-1186. Study Link
— “Patients with severe vitamin D deficiency had high rate of mortality (26.67%) as compared to patients with no vitamin D deficiency (7.5%)”


VII Bone Remodeling and Modeling at the Cellular Level

In adult life, 2 processes are responsible for changes in the skeleton: remodeling and modeling ( 128). Remodeling is the process by which new bone replaces old bone. It goes on continuously in both cortical and trabecular bone. Under physiological conditions, the shape and mass of bone are not affected by remodeling. During remodeling, bone cells called osteoblasts form new bone at specific sites after old bone is resorbed by large, multinucleated cells termed osteoclasts. This is often referred to as coupling, and the sites where it occurs are called bone multicellular units. In contrast to remodeling, modeling of bone is the process by which new bone is formed without prior resorption, or where resorption occurs without subsequent bone formation. Both the shape and mass of bone can be changed by modeling.

A Bone resorption

Remodeling is initiated by formation of osteoclasts, mainly on endosteal surfaces of trabecular and cortical bone, or within the Haversian canals in cortical bone. It also occurs at periosteal surfaces of cortical bone, although less frequently. Fully differentiated osteoclasts are large, multinucleated cells that can be identified in histological sections by their expression of the enzymes tartrate-resistant acid phosphatase (TRAP) and cathepsin K. For resorption to occur, osteoclasts must first seal off an area of bone. Osteoclasts are believed to bind to bone surfaces where outer, nonmineralized osteoid has been removed ( 129). The breakdown (resorption) of bone is initiated by dissolution of bone mineral crystals by a lowered pH (approximately 4.5). Protons are pumped into the “resorption lacunae beneath the ruffled border” by a proton pump expressed in the ruffled border of osteoclasts. In parallel with the mineral phase of bone being dissolved, osteoclasts release proteolytic enzymes that degrade type I collagen fibers and other noncollagen proteins in the bone matrix ( 130).

B Osteoclast proliferation, differentiation, and fusion

Multinucleated osteoclasts are formed by proliferation, differentiation, and fusion of mononuclear progenitor cells of myeloid hematopoietic origin ( Figure 4A). Macrophages and dendritic cells important for immune function arise from the same bone marrow progenitor pool of cells ( 131). For osteoclastogenesis to occur, progenitor cells must be activated by macrophage colony-stimulating factor (M-CSF), which is needed for proliferation and survival of osteoclasts, and by receptor activator of nuclear factor-κB (RANK) ligand (RANKL), which is required for osteoclast differentiation. M-CSF is expressed by many different cells, including osteoblasts in the periosteum and stromal cells in the bone marrow. RANKL is expressed more restrictively and was initially thought to be produced only by osteoblasts/bone marrow stromal cells and by T lymphocytes and to be involved in osteoclastogenesis and activation of dendritic cells ( 132). A variety of hormones, cytokines, and prostaglandins [eg, PTH, 1,25(OH)2 D3, IL-1, IL-6, IL-17, TNF-α, and prostaglandin E2], which stimulate bone resorption, were initially reported to increase RANKL in periosteal osteoblasts however, conditional deletion of Rankl in experimental studies has now suggested that expression of Rankl by osteocytes represents the most important source of RANKL for remodeling of the skeleton ( 133, 134).

Extra- and intracellular regulation of osteoclast formation. A, Osteoblasts on the surfaces of cortical and trabecular bone originate from pluripotent stromal cells present in bone marrow. These cells not only make bone but also control the formation of osteoclasts. Osteoblasts control differentiation of mononuclear progenitor cells to mature, multinucleated osteoclasts by expressing M-CSF and RANKL, which expand the number of myeloid progenitor cells and promote their differentiation, respectively. Genes up-regulated at different stages of osteoclast differentiation are shown in squares. Mononucleated osteoclasts fuse to latent multinucleated osteoclasts, which subsequently become activated and attach to mineralized bone surfaces. Activated osteoclasts resorb bone by dissolving hydroxyapatite crystals and degrading extracellular bone matrix proteins. B, M-CSF activates its cognate receptor c-Fms, leading to activation of intracellular signaling like PI3K and Akt, which are important for proliferation and survival of the progenitor cells. RANKL activates its receptor RANK, which will recruit TRAF6 and subsequently activate several kinases and downstream transcription factors. In the cytosol, the dimeric transcription factor NF-κB is bound to its inhibitor, IκBα activation of IKKβ by RANK signaling leads to phosphorylation of IκBα and dissociation from NF-κB, which then translocates to the nucleus and binds NF-κB response elements in DNA. Downstream signaling of RANK also involves activation of MAPK and phosphorylation of proteins like the c-Fos component of AP-1. These events are crucial for induction of Nfatc1, the master transcription factor of osteoclastogenesis. In its inactive form, Nfatc1 is phosphorylated, and activation is caused by dephosphorylation mediated by calcineurin, which is activated by signaling from FcRγ and/or DAP12 linked to Ig-like receptors expressed on the surface of osteoclasts. Nfatc1 acts in concert with other transcription factors like MITF, CREB, AP-1, and PU.1 to induce numerous genes necessary for osteoclast differentiation, fusion, and function. Osteoclast differentiation also requires down-regulation of genes such as Irf8, MafB, and Bcl6 associated with the macrophage phenotype. ITAM, immunoreceptor tyrosine-based activation motif. TREM-2, triggering receptor expressed on myeloid cells 2.

Extra- and intracellular regulation of osteoclast formation. A, Osteoblasts on the surfaces of cortical and trabecular bone originate from pluripotent stromal cells present in bone marrow. These cells not only make bone but also control the formation of osteoclasts. Osteoblasts control differentiation of mononuclear progenitor cells to mature, multinucleated osteoclasts by expressing M-CSF and RANKL, which expand the number of myeloid progenitor cells and promote their differentiation, respectively. Genes up-regulated at different stages of osteoclast differentiation are shown in squares. Mononucleated osteoclasts fuse to latent multinucleated osteoclasts, which subsequently become activated and attach to mineralized bone surfaces. Activated osteoclasts resorb bone by dissolving hydroxyapatite crystals and degrading extracellular bone matrix proteins. B, M-CSF activates its cognate receptor c-Fms, leading to activation of intracellular signaling like PI3K and Akt, which are important for proliferation and survival of the progenitor cells. RANKL activates its receptor RANK, which will recruit TRAF6 and subsequently activate several kinases and downstream transcription factors. In the cytosol, the dimeric transcription factor NF-κB is bound to its inhibitor, IκBα activation of IKKβ by RANK signaling leads to phosphorylation of IκBα and dissociation from NF-κB, which then translocates to the nucleus and binds NF-κB response elements in DNA. Downstream signaling of RANK also involves activation of MAPK and phosphorylation of proteins like the c-Fos component of AP-1. These events are crucial for induction of Nfatc1, the master transcription factor of osteoclastogenesis. In its inactive form, Nfatc1 is phosphorylated, and activation is caused by dephosphorylation mediated by calcineurin, which is activated by signaling from FcRγ and/or DAP12 linked to Ig-like receptors expressed on the surface of osteoclasts. Nfatc1 acts in concert with other transcription factors like MITF, CREB, AP-1, and PU.1 to induce numerous genes necessary for osteoclast differentiation, fusion, and function. Osteoclast differentiation also requires down-regulation of genes such as Irf8, MafB, and Bcl6 associated with the macrophage phenotype. ITAM, immunoreceptor tyrosine-based activation motif. TREM-2, triggering receptor expressed on myeloid cells 2.

Activation of the receptor RANK is dependent not only on the amount of RANKL present, but also on the amount of decoy receptor, osteoprotegerin (OPG), that is present. OPG is expressed ubiquitously and can bind RANKL, inhibiting binding to RANK. In addition to signaling through RANK and the c-Fms receptor for M-CSF, stimulation of the adapter proteins Fc receptor common γ-subunit (FcRγ) and DNAX activating protein of 12 kDa (DAP12), which are dimerized to Ig-like receptors such as osteoclast-associated receptor (OSCAR) and triggering receptor expressed on myeloid cells 2 (2), is required for stimulation of osteoclast differentiation ( 132). Genetic experiments have shown that mice overexpressing OPG, or with a deletion of RANKL, RANK, or c-Fms, or double knockout of FcRγ/DAP12, lack osteoclasts and exhibit osteopetrosis. Osteopetrosis is also observed in mice with a mutation in the gene encoding M-CSF. In contrast, mice lacking OPG exhibit early-onset osteoporosis ( 131, 132).

At a certain stage, mononuclear osteoclasts will fuse to latent multinucleated osteoclasts, which eventually will be activated to polarized bone-resorbing osteoclasts. The fusion process is not well understood, but dendritic cell-specific transmembrane protein (Dc-stamp) seems to be involved ( 135).

C RANK/c-Fms/FcRγ-DAP12 intracellular signaling

Intracellular signaling events downstream of RANK/c-Fms/FcRγ-DAP12 have been extensively investigated during the past decade ( Figure 4B). The intracellular tail of RANK expresses several binding sites for TNF-related associated factors (TRAFs), of which TRAF6 seems to be most important ( 131, 132). Subsequent, proximal events include activation of several kinases, including MAPKs, inhibitor of nuclear factor-κB (NF-κB) kinase β (IKKβ), phosphoinositide 3-kinase (PI3K), and Akt. FcRγ/DAP12 signaling causes activation of phospholipase Cγ (PLCγ), a rise of intracellular calcium, and subsequent activation of the phosphatase calcineurin. Downstream events include activation of several transcription factors, such as NF-κB, c-Fos containing AP-1 (activator protein-1), nuclear factor of activated T cells c1 (Nfatc1), CREB, microphthalmia-associated transcription factor (MITF), and PU.1, which cooperate to regulate a multitude of genes (eg, Calcr [calcitonin receptor], Acp5 [TRAP], Ctsk [cathepsin K], Atp6i [proton pump subunit], αvβ3 [vitronectin receptor], Clcn7 [chloride channel 7], and Dc-stamp) that are important for osteoclast differentiation, fusion, and function. In addition, several transcription factors, including v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB), interferon regulatory factor-8 (IRF-8), and B-cell lymphoma 6 (Bcl6), negatively regulate osteoclastogenesis ( 136), and the expression of these factors is repressed during osteoclast differentiation.

In vitro experiments have shown that mature osteoclasts can be formed from progenitor cells present in bone marrow, spleen, peripheral blood, and periosteum if M-CSF and RANKL are used as stimulators. However, the extent to which osteoclast-inducing hormones and cytokines affect progenitor cells in bone marrow, spleen, the circulation, or periosteum/endosteum is less clear, and it is not known whether there are differences in phenotypes of the progenitors from different sources. It has been reported that mature osteoclasts exhibit more phenotypic variation than realized previously, suggesting that progenitor cells from different sites might exhibit significant differences also ( 137).


by J. Clifford and A. Kozil* (9/17)

Quick Facts…

  • Small amounts of vitamin A, vitamin D, vitamin E and vitamin K are needed to maintain good health.
  • Fat-soluble vitamins will not be lost when the foods that contain them are cooked.
  • The body does not need these vitamins every day and stores them in the liver and adipose (fat) tissue when not used.
  • Most people do not need vitamin supplements.
  • Megadoses of vitamins A, D, E or K can be toxic and lead to health problems.
  • Requirements for vitamins may be expressed in different mathematical units. Close attention should be paid to ensure that similar units are being compared.

What are Vitamins?

Vitamins are essential micronutrients required by the body in small amounts to support a range of vital functions. Vitamins are divided into two groups: water-soluble (B-complex vitamins and C
vitamins) and fat-soluble vitamins (A, D, E and K). Unlike water-soluble vitamins that need regular replacement in the body, fat-soluble vitamins are stored in the liver and fatty tissues, and are
eliminated much more slowly than water-soluble vitamins. For more information on water-soluble vitamins, see fact sheet 9.312 Water-Soluble Vitamins: Vitamin B-Complex and Vitamin C.

What are Fat-Soluble Vitamins?

The fat-soluble vitamins, A, D, E, and K, are stored in the body for long periods of time and generally pose a greater risk for toxicity than water-soluble vitamins when consumed in excess. Eating a normal, well-balanced diet will not lead to toxicity in otherwise healthy individuals. However, taking vitamin supplements that contain megadoses of vitamins A, D, E and K may lead to toxicity.

While diseases caused by a lack of fat-soluble vitamins are rare in the United States, symptoms of mild deficiency can develop without adequate amounts of vitamins in the diet. Additionally, some
health problems, such as inflammatory bowel disease (IBD), chronic pancreatitis, and cystic fibrosis, may decrease the absorption of fat, and in turn, decrease the absorption of vitamins A, D, E and K. Consult a medical professional about any potential health problems that may interfere with vitamin absorption.

Vitamin A: Retinol

What is Vitamin A?

Vitamin A, also called retinol, has many functions in the body. In addition to helping the eyes adjust to light changes, vitamin A plays an important role in bone growth, tooth development, reproduction, cell division, gene expression, and regulation of the immune system. The skin, eyes, and mucous membranes of the mouth, nose, throat and lungs depend on vitamin A to remain moist. Vitamin A is also an important antioxidant that may play a role in the prevention of certain cancers.

Food Sources for Vitamin A

Eating a wide variety of foods is the best way to ensure that the body gets enough vitamin A. The retinol, retinal, and retinoic acid forms of vitamin A are supplied primarily by foods of animal origin such as dairy products, fish and liver. Some foods of plant origin contain the antioxidant, beta-carotene, which the body converts to vitamin A. Beta-carotene, comes from fruits and vegetables, especially those that are orange or dark green in color. Vitamin A sources also include carrots, pumpkin, winter squash, dark green leafy vegetables and apricots, all of which are rich in betacarotene.

How Much Vitamin A Do We Need?

The recommendation for vitamin A intake is expressed as micrograms (mcg) of retinol activity equivalents (RAE). Retinol activity equivalents account for the fact that the body converts only a portion of beta-carotene to retinol. One RAE equals 1 mcg of retinol or 12 mcg of beta-carotene (Table 1). The Recommended Dietary Allowance (RDA) for vitamin A is 900 mcg/ day for adult males and 700 mcg/day for adult females.

Compared to vitamin A containing foods, it takes twice the amount of carotene rich foods to meet the body’s vitamin A requirements, so one may need to increase consumption of carotene containing plant foods to meet the RDA for vitamin A.

Studies indicate that vitamin A requirements may be increased due to hyperthyroidism, fever, infection, cold, and exposure to excessive amounts of sunlight. Those who consume excess alcohol or have renal disease should also increase intake of vitamin A.

Vitamin A Deficiency

Vitamin A deficiency in the United States is rare, but the disease that results is known as xerophthalmia, which can lead to blindness if untreated. It most commonly occurs in developing nations usually due to malnutrition. Since vitamin A is stored in the liver, it may take up to 2 years for signs of deficiency to appear. Night blindness and very dry, rough skin may indicate a lack of vitamin A. Other signs of possible vitamin A deficiency include decreased resistance to infections, faulty tooth development, and slower bone growth. Vitamin A deficiency is also a known risk factor for severe measles. According to the World Health Organization (WHO), Vitamin A supplementation can significantly reduce mortality rates for children with measles who live in areas with a high prevalence of Vitamin A deficiency. The effectiveness of vitamin A supplementation to treat measles in countries, such as the United States, where vitamin A intakes are generally adequate, is uncertain.

Too much Vitamin A

In the United States, toxic or excess levels of vitamin A are more of a concern than deficiencies. The Tolerable Upper Intake Level (UL) for adults is 3,000 mcg RAE (Table 2). It would be difficult to reach this level consuming food alone, but some multivitamin supplements contain high doses of vitamin A. Retinol is the form of vitamin A that causes the greatest concern for toxicity. If you take a multivitamin, check the label to be sure the majority of vitamin A provided is in the form of beta-carotene, which appears to be safe. Some medications used to treat acne, psoriasis, and other skin conditions contain compounds that mimic retinol in the body. Much like excessive intake of dietary retinol, these medications have been shown to negatively impact bone health and result in delayed growth in children and teens.

Symptoms of vitamin A toxicity include dry, itchy skin, headache, nausea, and loss of appetite. Signs of severe overuse over a short period of time include dizziness, blurred vision and slowed growth. Vitamin A toxicity can also cause severe birth defects and may increase the risk for bone loss and hip fractures.

Vitamin D

What is Vitamin D?

Vitamin D plays a critical role in the body’s use of calcium and phosphorous. It works by increasing the amount of calcium absorbed from the small intestine, helping to form and maintain bones. Vitamin D benefits the body by playing a role in immunity and controlling cell growth and may protect against osteoporosis, high blood pressure, cancer, and other diseases. Children especially need adequate amounts of vitamin D to develop strong bones and healthy teeth.

Food Sources for Vitamin D

The primary food sources of vitamin D are milk and other dairy products fortified with vitamin D. Vitamin D is also found in oily fish (e.g., herring, salmon and sardines) as well as in cod liver oil. In addition to the vitamin D provided by food, we obtain vitamin D through our skin which produces vitamin D in response to sunlight.

How much Vitamin D Do We Need?

The Recommended Dietary Allowance (RDA) for vitamin D appears as micrograms (mcg) of cholecalciferol (vitamin D3) (Table 1). From 12 months to age fifty, the RDA is set at 15 mcg. Twenty mcg of cholecalciferol equals 800 International Units (IU), which is the recommendation for maintenance of healthy bone for adults over fifty. Table 1 lists additional recommendations for various life stages.

Exposure to ultraviolet light is necessary for the body to produce the active form of vitamin D. Ten to fifteen minutes of sunlight without sunscreen on the hands, arms and face, twice a week is sufficient to receive enough vitamin D. This can easily be obtained in the time spent riding a bike to work or taking a short walk with arms and legs exposed. In order to reduce the risk for skin cancer one should apply sunscreen with an SPF of 15 or more, if time in the sun exceeds 10 to 15 minutes.

Vitamin D Deficiency

Symptoms of vitamin D deficiency in growing children include rickets (long, soft bowed legs) and flattening of the back of the skull. Vitamin D deficiency in adults may result in osteomalacia (muscle and bone weakness), and osteoporosis (loss of bone mass). Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious disease.Research shows that vitamin D insufficiency affects almost 50% of the population worldwide an estimated 1 billion people. The rising rate of deficiency has been linked to a reduction in outdoor activity and an increase in the use of sunscreen among children and adults. In addition, those who live in inner cities, wear clothing that covers most of the skin, or live in northern climates where little sun is seen in the winter are also prone to vitamin D deficiency. Since most foods have very low vitamin D levels (unless they are enriched) a deficiency may be more likely to develop without adequate exposure to sunlight. Adding fortified foods to the diet such as milk, and for adults including a supplement, are effective at ensuring adequate vitamin D intake and preventing low vitamin D levels. In the absence of adequate sun exposure, at least 800 to 1,000 IU of vitamin D3 may be needed to reach the circulating level required to maximize vitamin D’s benefits.

Who is at Risk — These populations may require extra vitamin D in the form of supplements or fortified foods:

  • Exclusively breast-fed infants: Human milk only provides 25 IU of vitamin D per liter. All breast-fed and partially breast-fed infants should be given a vitamin D supplement of 400 IU/day.
  • Dark Skin: Those with dark pigmented skin synthesize less vitamin D upon exposure to sunlight compared to those with light pigmented skin.
  • Elderly: This population has a reduced ability to synthesize vitamin D upon exposure to sunlight, and is also more likely to stay indoors and wear sunscreen which blocks vitamin D synthesis.
  • Covered and protected skin: Those that cover all of their skin with clothing while outside, and those that wear sunscreen with an SPF factor of 8, block most of the synthesis of vitamin D from sunlight.
  • Disease: Fat malabsorption syndromes, inflammatory bowel disease (IBD), and obesity are all known to result in a decreased ability to absorb and/or use vitamin D in fat stores.

Too much Vitamin D


The Tolerable Upper Intake Level (UL) for vitamin D is set at 100 mcg (4000 IUs) for people 9 years of age and older (Table 2). High doses of vitamin D supplements coupled with large amounts of fortified foods may cause accumulations in the liver and produce signs of poisoning. Signs of vitamin D toxicity include excess calcium in the blood, slowed mental and physical growth, decreased appetite, nausea and vomiting.

It is especially important that infants and young children do not consume excess amounts of vitamin D regularly, due to their small body size.

Vitamin E: Tocopherol

What is Vitamin E?

Vitamin E benefits the body by acting as an antioxidant, and protecting vitamins A and C, red blood cells, and essential fatty acids from destruction. Research from decades ago suggested that taking antioxidant supplements, vitamin E in particular, might help prevent heart disease and cancer. However, newer findings indicate that people who take antioxidant and vitamin E supplements are not better protected against heart disease and cancer than non-supplement users. Many studies show a link between regularly eating an antioxidant rich diet full of fruits and vegetables, and a lower risk for heart disease, cancer, Alzheimer’s Disease, and several other diseases. Essentially, research indicates that to receive the full benefits of antioxidants and phytonutrients in the diet, one should consume these compounds in the form of fruits, vegetables, nuts, and seeds, not as supplements.

Food Sources for Vitamin E

About 60 percent of vitamin E in the diet comes from vegetable oil (soybean, corn, cottonseed, and safflower). This also includes products made with vegetable oil (margarine and salad dressing). Vitamin E sources also include fruits and vegetables, grains, nuts (almonds and hazelnuts), seeds (sunflower) and fortified cereals.

How much Vitamin E Do We Need?

The Recommended Dietary Allowance (RDA) for vitamin E is based on the most active and usable form called alpha-tocopherol (Table 1). Food and supplement labels list alpha-tocopherol as the unit international units (IU) or micrograms (mcg), not in milligrams (mg). One microgram of alpha-tocopherol equals to 1.5 International units (IU). RDA guidelines state that males and females over the age of 14 should receive 15 mcg (22.5 IUs) of alpha-tocopherol per day. Consuming vitamin E in excess of the RDA does not result in any added benefits.

Vitamin E Deficiency

Vitamin E deficiency is rare. Cases of vitamin E deficiency usually only occur in premature infants and in those unable to absorb fats. Since vegetable oils are good sources of vitamin E, people who excessively reduce their total dietary fat may not get enough vitamin E.

Too much Vitamin E

The Tolerable Upper Intake Level (UL) for vitamin E is shown in Table 2.Vitamin E obtained from food usually does not pose a risk for toxicity. Supplemental vitamin E is not recommended due to lack of evidence supporting any added health benefits. Megadoses of supplemental vitamin E may pose a hazard to people taking blood-thinning medications such as Coumadin (also known as warfarin) and those on statin drugs.

Vitamin K

What is Vitamin K?

Vitamin K is naturally produced by the bacteria in the intestines, and plays an essential role in normal blood clotting, promoting bone health, and helping to produce proteins for blood, bones, and kidneys.

Food Sources for Vitamin K

Good food sources of vitamin K are green, leafy-vegetables such as turnip greens, spinach, cauliflower, cabbage and broccoli, and certain vegetables oils including soybean oil, cottonseed oil, canola oil and olive oil. Animal foods, in general, contain limited amounts of vitamin K.

How much Vitamin K Do We Need?

To help ensure people receive sufficient amounts of vitamin K, an Adequate Intake (AI) has been established for each age group (Table 1).

Vitamin K Deficiency


Without sufficient amounts of vitamin K, hemorrhaging can occur. Vitamin K deficiency may appear in infants or in people who take anticoagulants, such as Coumadin (warfarin), or antibiotic drugs. Newborn babies lack the intestinal bacteria to produce vitamin K and need a supplement for the first week. Those on anticoagulant drugs (blood thinners) may become vitamin K deficient, but should not change their vitamin K intake without consulting a physician. People taking antibiotics may lack vitamin K temporarily because intestinal bacteria are sometimes killed as a result of long-term use of antibiotics. Also, people with chronic diarrhea may have problems absorbing sufficient amounts of vitamin K through the intestine and should consult their physician to determine if supplementation is necessary.

Too much Vitamin K

Although no Tolerable Upper Intake Level (UL) has been established for vitamin K, excessive amounts can cause the breakdown of red blood cells and liver damage. People taking blood-thinning drugs or anticoagulants should moderate their intake of foods with vitamin K, because excess vitamin K can alter blood clotting times. Large doses of vitamin K are not advised.

Summary

  • Fat-soluble vitamins: A, D, E, and K —are stored in the body for long periods of time, and pose a greater risk for toxicity than water-soluble vitamins. Fat-soluble vitamins are only needed in small amounts.
  • Beta carotene is an important antioxidant that the body converts to Vitamin A,and it is found in a variety of fruits and vegetables.
  • Inadequate dietary consumption of vitamin D, along with limited sun exposure, makes vitamin D deficiency a growing public health concern.
  • Vitamin E benefits the body by acting as an antioxidant, and research indicates that it may offer a protective effect if obtained through a diet rich in fruits and vegetables, as opposed to a supplement or multivitamin.
  • The bacteria in our gut produce vitamin K, and it is also found in green leafy vegetables.

Table 1. Recommended Dietary Intake (RDA) and Adequate Intake (AI) for Fat-Soluble Vitamins

Life Stage Group Vitamin A
(mcg 1 /RAE)
Vitamin D
(mcg 2 )
Vitamin E
(mcg a-TE 3 )
Vitamin K
(mcg)
Infants 4
0 – 6mo 400* 10* 4* 2.0*
6mo – 12mo 500* 10* 5* 2.5*
Children
1 – 3y 300 15 6 30*
4 – 8y 400 15 7 55*
Males
9 – 13y 600 15 11 60*
14 – 18y 900 15 15 75*
19 – 30y 900 15 15 120*
31 – 50y 900 15 15 120*
51 – 70y 900 15 15 120*
>70y 900 20 15 120*
Females
9 – 13y 600 15 11 60*
14 – 18y 700 15 15 75*
19 – 30y 700 15 15 90*
31 – 50y 700 15 15 90*
51 – 70y 700 15 15 90*
>70y 700 20 15 90*
Pregnant
14 – 18y 750 15 15 75
19 – 30y 770 15 15 90
31 – 50y 770 15 15 90
Lactation
14 – 18y 1200 15 19 75
19 – 30y 1300 15 19 90
31 – 50y 1300 15 19 90

1 As retinol activity equivalents (RAEs). 1 RAE = 1mcg retinol or 12 mcg beta-carotene.

2 As cholecalciferol (vitamin D3). 10 mcg cholecalciferol = 400 IU of Vitamin D.

3 As alpha-tocopherol equivalents. 1 mg of alpha-tocopherol = 1.5 IU of Vitamin E=22IU of d-alpha-tocopherol=33 IU of dl-alpha- tocopherol

4 At 6 months of age, infants may be introduced to solid foods while remaining on formula or breast milk. There may be some overlap in specific nutrient requirements.

*Indicates an Adequate Intake (AI). All other values are Recommended Dietary Allowance (RDA).

Table 2. Tolerable Upper Intake Levels (UL) for Fat-Soluble Vitamins

Life Stage Group Vitamin A
(mcg/d)
Vitamin D
(mcg/d)
Vitamin E
(mg a-TE)
Vitamin K*
Infants 1
0 – 6mo 600 25 ND 2 ND
6mo – 12mo 600 38 ND ND
Children
1 – 3y 600 63 200 ND
4 – 8y 900 75 300 ND
Males/Females
9 – 13y 1700 100 600 ND
14 – 18y 2800 100 800 ND
19 – 70y 3000 100 1000 ND
>70y 3000 100 1000 ND
Pregnant and Lactating
<18 2800 100 800 ND
19 – 50y 3000 100 1000 ND

1 At 6 months of age, infants may be introduced to solid foods while remaining on formula or breast milk. There may be some overlap in specific nutrient requirements.

2 ND = not determinable due to insufficient data

*An UL for vitamin K was not established.

References

Berdanier, C., Berdanier, L., Zempleni, J. (2009). Advanced Nutrition: Macronutrients, Micronutrients, and Metabolism. Boca Raton, FL: CRC Press, Taylor & Francis Group.

Duyff, R. (2012). American Dietetic Association: Complete Food and Nutrition Guide. Hoboken, NJ: John Wiley & Sons, Inc.

Gropper, S., Smith, J. (2009).Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth, Cengage Learning.

Holick, M., Chen, T. (2008). Vitamin D deficiency: a worldwide problem with health consequences. American Journal of Clinical Nutrition, 87 (4), 1080-1086.

Institute of Medicine (US). (2002). Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press.

Institute of Medicine (US). (2000). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press.

Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium Ross A., Taylor, C., Yaktine, A., et al., editors. (2011). Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK56070/ doi: 10.17226/13050.

* J. Clifford, Colorado State University Extension food and nutrition specialist , A. Kozil, graduate student. Original fact sheet revised by L. Bellows, Colorado State University Extension food and nutrition specialist and assistant professor and R. Moore, graduate student. 11/2012 . Revised 9/17.