Vitamin D deficiency: what are the effects of low vitamin D?

 

Vitamin D deficiency – also known as vitamin D3 deficiency – affects a hefty one billion people around the world. We can only acquire enough of this essential vitamin – also known as the sunshine vitamin – with sufficient exposure to the sun or by taking the right vitamin D supplements.

Hair loss, depression, fatigue, skin diseases, and cancer are some of the short-term and long-term effects associated with vitamin D deficiency. Studies have shown that vitamin D plays a role in numerous processes in the body. It impacts bone, muscle, immune system, and blood vessel function – and much more. As a result, vitamin D has been a hot topic not only among scientists and physicians over recent years, but also in the media, in weekly magazines, television programs and social media.

Despite the media hype and the new awareness surrounding vitamin D, few people manage to take in enough. It is estimated that one billion people in the world have low vitamin D intake. According to a study carried out, around one-third of adults in the United Kingdom have insufficient vitamin D levels, especially during wintertime – that is, between January and March.^[60]

What is the role of vitamin D in the body, and what are the effects of low vitamin D? We’ll cover all this and tell you more about vitamin D deficiency symptoms, how to check vitamin D levels through testing, optimal vitamin D intake and which supplements you can take to ensure that you are optimally supplied with vitamin D.

What is vitamin D?

Vitamin D is a fat-soluble vitamin, with experts also referring to it as a hormone. This is because it has a hormone-like effect, and we don’t consume it primarily through our diet, as is otherwise normal with other vitamins. Instead, our body produces vitamin D itself, but requires UVB radiation from the sun to produce it. It is therefore not for nothing that vitamin D is also called the sun vitamin.

The two most important forms of vitamin D are vitamin D₂ (ergocalciferol), which is found in plants, and vitamin D₃ (cholecalciferol), also called 25-(OH)-D.^[2] The latter form of vitamin D is found in animal tissue. Our bodies produce vitamin D when sunlight breaks down the chemical bonds of the chemical precursor of vitamin D, 7-dehydrocholesterol, which, itself, is found in our skin.

There, the active form of the vitamin – namely, vitamin D3 – is produced, and this in turn becomes 25-hydroxy-cholecalciferol (25-OH-D), the storage form of vitamin D, which is then stored in our muscles and adipose tissue. In the kidney, 25-OH-D is converted to 1,25-(OH)2-D, which is transported through our blood to our intestine, bones, muscles, immune system and cells where it carries out further important bodily functions.^[5]

What is the role of vitamin D in the body?

Vitamin D is involved in numerous processes within the body, attributable particularly to its dual role as both a vitamin and a hormone. Among its most important tasks is its role in bone metabolism and muscle development and function. In addition, vitamin D boosts our immune system health and protects blood vessels.^[2]

Other functions of vitamin D include:

• controlling calcium and phosphate absorption in the small intestine;
• regulating more than 200 genes;
• promoting heart muscle function;
• functioning as a hypotensive mediator and
• promoting skeletal development in children.

How much vitamin D do I need?

With vitamin D, it is important to maintain sufficient levels, and a reliable daily dose is difficult to determine because we also receive different amounts of vitamin D in different seasons. The best way is to check vitamin D levels in your blood. You can have your 25-(OH)-D blood levels measured – this might be given, for instance, in nanogrammes per millilitre.^[34]

• Your vitamin D levels are sufficient if your concentration of vitamin D is 30 nanogrammes per millilitre of blood.
• Values below 11 nanogrammes per millilitre are considered to be critical and can encourage disorders such as bone loss – also known as osteoporosis.
• Some researchers argue that 60 nanogrammes or more of vitamin D per millilitre of blood will ensure you enjoy all health benefits the sun vitamin has to offer.

What is vitamin D deficiency?

It is estimated that about one billion people globally are affected by vitamin D deficiency – or vitamin D3 deficiency.^{[9, 10]} Various studies have linked vitamin D deficiency to chronic diseases such as osteoporosis, diabetes, cancer, depression, cardiovascular disease and a weakened immune system.^[14–17]

Who is most affected by vitamin D deficiency?

In general, vitamin D deficiency occurs in all age groups and social groups, and in areas as diverse as Europe, South America and the Middle East. That being said, you should be aware that there are certain risk groups. If you belong to one of these groups, you should regularly check vitamin D levels and, if necessary, take supplements.

The risk groups include:^[18]

• people who are predominantly indoors or who cover their bodies when they are outdoors;
• pregnant women, since they also have a higher vitamin D requirement
• people with a dark skin type because their bodies produce less vitamin D than people with fair skin
• elderly people, since vitamin D production decreases significantly in old age – and they may often not be outdoors, for mobility reasons
• babies, since the vitamin D content in breast milk is low and they should not be exposed to direct sunlight

To find out more about the ideal diet during breastfeeding and pregnancy – as well as which other important vitamins and minerals your body needs – head over to our dedicated Health Portal blog article.

Vitamin D deficiency causes: what do I need to know?

Vitamin D deficiency occurs because we do not get enough sun. While our ancestors stayed primarily outdoors, we spend most of our time indoors. And we also cover our bodies with clothing and protect ourselves with sun cream. All of this reduces the effects of UVB on the skin – and that’s precisely what our body needs to produce vitamin D.^[19]

Did you know that by applying a sun cream with a sun protection factor of 30, vitamin D synthesis in our skin is reduced by more than 95 per cent?^[31]

Several other factors can also interfere with our body’s vitamin D production. These vitamin D deficiency causes, include – for example:^[2]

• diseases that impair fat digestion and ingestion, such as coeliac disease, bile acid deficiency or pancreatic insufficiency; and
• certain medications such as antihypertensives, antiestrogens, cytostatics, antiepileptics and herbal medicines.

Vitamin D deficiency causes: why are older adults prone to vitamin D deficiency?

From 60 years onwards, vitamin D deficiency is particularly common. This is not always because older people rarely go outdoors – their body in fact produces down to four times less vitamin D than younger people. If you are over 60, you should regularly check vitamin D levels and counter any deficiencies with supplements.^[22-25]

Taking the right dosage of vitamin D supplements is incredibly beneficial, as it can prevent or alleviate many health complaints encountered frequently in old age. Positive effects confirmed in studies include:^{[22, 26-29]}

• reduced risk of bone fractures;
• better cardiovascular health;
• reduced cancer risk, such as colon cancer;
• better balance; and
• greater muscle power.

What are common vitamin D deficiency symptoms?

Vitamin D deficiency symptoms are rarely noticeable; they are often generic and hidden, and include fatigue, muscle fatigue, musculoskeletal pain and headaches.^[1] As a result, many people do not notice they suffer from low vitamin D levels until they develop into more serious health conditions. One of the most common effects of low vitamin D is osteomalacia (bone softening).^[19]

Those who have a severe chronic vitamin D deficiency are at an increased risk of:^[19]

• osteomalacia and osteoporosis
• rickets in children
• pain and weakness in the bones (osteoarthritis)
• bone fractures in seniors over 65 (broken bones)

In addition, recent study results have associated a vitamin D deficiency with a number of diseases. The diseases often occur together with the deficiency, and researchers are still investigating how strongly vitamin D deficiency is connected with the following conditions:^{[20, 21]}

• hypertension and heart disease,
• diabetes,
• depression,
• serious infections such as tuberculosis and chronic kidney disease and
• hair loss.

What are the effects of low vitamin D?

In recent years, scientists have spent considerable time studying how vitamin D levels impact our overall health. We’ll now present you with a series of studies that show the links between vitamin D and various diseases and health problems.

Vitamin D and depression: can vitamin D affect mood?

Studies have shown that vitamin D deficiency impacts mental health. Among other things, depression, stress, mood swings and anxiety can all be linked to low vitamin D levels.^[48]

The relationship between low vitamin D levels and depression has already been studied. People with depression have significantly lower vitamin D levels than people who aren’t depressed.^[48] Some studies suggest that vitamin D supplements might improve depressive symptoms in people with vitamin D deficiency, but evidence gathered to date does not allow for any specific recommendations to be made.

Does vitamin D help with sleep?

In 2017 Iranian scientists investigated the effect of vitamin D on sleep quality. A total of 89 participants with sleep disorders aged 20 to 50 years were administered either a vitamin D supplement or a placebo.

The result was that the participants who received vitamin D found that the quality of their sleep significantly improved, they slept for longer, and it took them less time to fall asleep compared with individuals who did not receive the vitamin D supplement. In another study, people with low vitamin D levels endured a poorer sleep quality.^[49]

Besides vitamin D, there are other sleep improvement supplements that have been proven to boost the quality of your sleep – including melatonin, magnesium, 5-HTP and valerian – among many others. If you’re struggling with sleeping, you can discuss taking these supplements with your doctor.

Are vitamin D and hair loss linked?

For some time it has been known that vitamins and minerals affect hair growth. For instance, iron, biotin, and zinc are important for healthy hair roots.^[50] Studies conducted in test tubes suggest that vitamin D might also be involved in active hair growth.

Vitamin D as such promotes the production of receptors in hair roots, which then stimulate growth. Up until now, however, no conclusive and informative clinical studies have been published that can confirm this theory.

Can a lack of vitamin D cause migraines?

A migraine is a severe headache that keeps on coming back. Experts now believe that migraine episodes develop as a result of inflammation in the nerves and blood vessels.^[51] Researchers are currently investigating whether vitamin D supplements can inhibit the inflammatory factors that contribute to migraines. The fact that vitamin D is anti-inflammatory has been confirmed in other studies.^[52]

However, at present, there are still relatively few studies in this area and the research results are still inconsistent. Some have revealed a connection between vitamin D and migraines, and in one study it was shown that taking vitamin D could reduce the frequency of headaches.^[52] In other studies, however, vitamin D did not have an impact on migraines.

Skin problems and vitamin D: Is vitamin D good for your skin?

Vitamin D also seems to play a role in our skin health. The vitamin clearly contributes to wound healing and allowing our epidermis to develop properly. vitamin D deficiency may therefore contribute towards the development of skin diseases such as eczema (atopic eczema), psoriasis and white spot disease (vitiligo).^[53]

Studies have shown promising results regarding vitamin D supplementation and atopic (neuro)dermatitis. Eczema patients are very susceptible to bacterial skin infections – in one study, patients with low vitamin D levels were particularly likely to suffer from such infections.^[54] Researchers are also investigating how vitamin D supplements can positively impact psoriasis and vitiligo (white spot disease).^[55]

What are the effects of vitamin D on cardiovascular health?

Vitamin D, according to research, can strengthen the heart muscle. In addition, vitamin D carries out an important role when it comes to calcium and phosphate metabolism. The sun vitamin ensures that calcium and phosphate are stored in the bones. If you suffer from vitamin D deficiency, calcium in particular is not stored properly and instead settles in the blood vessels, which can sometimes lead to calcification.^[46]

A study published in the American Journal of Cardiology in 2012 revealed that vitamin D deficiency may increase the risk of dying from cardiovascular disease. Vitamin D supplements reduced this risk in the same study. The study authors assumed that vitamin D deficiency is a risk factor for heart disease, cardiac muscle problems and high blood pressure.^[56]

These results were confirmed by another study involving over 40,000 patients. Subjects with vitamin D levels of less than 15 nanogrammes per millilitre were more likely to experience hypertension, elevated blood lipid levels, heart defects and strokes than those with vitamin D levels of 30 nanogrammes per millilitre.^[56]

Another supplement that is known to boost your heart health is omega 3. This nutrient can also be found in certain foods, such as fatty fish and coconut oil. To read more about the benefits of omega 3, head over to our Health Portal article.

Does vitamin D help with osteoporosis?

Not only calcium but also vitamin D are crucial for optimal bone health. When it comes to preventing osteoporosis and bone loss or fractures, calcium and vitamin D supplementation are considered absolutely vital.

Functions of vitamin D include regulating calcium absorption and stimulating bone resorption. If you don’t treat your vitamin D deficiency, calcium continues to be pulled from your bones, leading to rickets can occur in children and osteomalacia and osteoporosis in adults.

Bone loss generally occurs without symptoms – and osteoporosis is considered a ‘silent disease’. Fractures or injuries that have occurred due to osteoporosis or bone softening can lead to chronic pain, disability and psychological symptoms, such as depression.^[60] For more information about preventing osteoporosis and the symptoms and causes of osteoporosis, visit our Health Portal blog article.

Is vitamin D deficiency related to cancer?

Vitamin D is considered by many to be a ray of hope when it comes to preventing cancer. Study results until now, however, have proven ambiguous. Individual studies found links, for instance, between vitamin D levels and the risk of colon cancer and breast cancer.^[57]

Current large-scale studies, however, found that vitamin D intake had no influence on the development of tumours. Many scientists say that more research is required before anything more concrete can be stated. Studies dealing with this topic are currently ongoing, some of which are also investigating the effects of high-dose vitamin D supplements on cancer development.

Covid-19 and Vitamin D: is there a link?

You’ve no doubt heard a multitude of times from various sources that the global pandemic has transformed our lives in unprecedented ways. As frustrated as we may be with hearing this phrase, it is certainly true when it comes to our vitamin D levels. 

Dermatologists have warned that our new routines require vitamin D supplements. With more people working from home these days – and therefore less people commuting than before the pandemic – it is essential for us to make sure we are getting that all-important exposure to the sun. Even during the winter months! Don’t forget that travel restrictions and fear to venture abroad have meant that fewer people are willing to go on their usual summer holiday. Those vital annual vitamin D reserves might therefore be lower than normal for some people.

So, what about the importance of vitamin D supplements in the fight against the coronavirus itself? Studies are currently being conducted to inspect in further detail just how effective vitamin D could be in terms of fighting Covid-19. Currently, there only seems to be reported and unverified links between a vitamin D deficiency and the severity of the virus; however, a study published in January 2021 by BMJ Nutrition, Prevention and Health has revealed that there is no evidence of vitamin D being protective against CovidD-19.^[58]

Check vitamin D levels: how do you test for vitamin D?

Many factors are involved in regulating your supply of vitamin D and avoiding a deficiency. Without a test, it’s difficult to say how you should best optimise your intake. In order to find out if and how you should supplement vitamin D, a vitamin D Test is certainly worthwhile – especially if you belong to one of the at-risk groups.

The most common measurements are blood tests performed by a doctor. With a home health test, you can also check your levels from the comfort of your home. To do this, take a blood sample yourself by pricking your finger and sending it to a specialist laboratory. The laboratory will then analyse the level of 25-(OH)-D in your blood serum. Afterward, the lab usually sends you a results report telling you where your values are at and how to get your vitamin D levels back on track (and keep it on track) using vitamin D supplements.

You should not take any vitamin D supplements without first having a blood test. Unlike other vitamins, you cannot get rid of vitamin D through your urine. If your vitamin D levels are already good, and you still take long-term high-dose supplements, you might overdose on vitamin D. Too much vitamin D can trigger symptoms such as nausea, vomiting, cardiac arrhythmia and dysregulation – and in the long term, weight loss, kidney stones and organ damage.^{[2, 5]}

What is the best treatment for vitamin D deficiency?

How long we need to lie in the sun to produce enough vitamin D depends on many factors, including our skin type, the latitude we live in, the time of day and the time of year. According to experts, over summer, it is usually enough to expose our face, hands and arms to direct sunlight three times a week for ten to twenty minutes.

To produce 400 IU of vitamin D, a person with medium-light skin (one who tans slowly and rarely gets sunburn) on the 42nd line of latitude from April to October (for example, in southern France) should expose a quarter of their skin (for example, arms, face, neck) for about three to eight minutes at midday in the sun.

Many people across the globe are not able to expose themselves to enough sun in the summer – and this is even more impossible in the winter. In winter, the sun rarely shines in northern latitudes, and its light also contains too little UVB radiation. It is barely possible to produce adequate vitamin D.^[1]

Researchers and professional institutions are therefore discussing how much vitamin D we should consume via dietary supplements if an adequate supply cannot be guaranteed due to insufficient sun exposure.

Please note: do not overdo it while sunbathing. A few minutes without UV protection are useful for boosting vitamin D production, but too much direct sunlight can lead to sunburn and increase the risk of skin cancer. Curious about the ideal summer skin care regime? Check out our blog article on summer skin care and sun allergy.

Vitamin D in Our Diet: how can I boost my vitamin D?

Our small intestine can absorb up to 80 per cent of the fat-soluble vitamin D3 consumed in food.^[5] Despite this, our body only absorbs relatively small amounts of vitamin D into the body this way; we only cover about 10 to 20 per cent of our  daily vitamin D requirement through our diet.

This is partly due to the fact that few foods contain vitamin D, and when they do, they only contain small quantities. Vitamin D3, which is important for the body, is found almost exclusively in animal foods, and more specifically in:^{[2, 5]}

• fatty fish such as herring or kippers;
• margarine and butter and
• milk and egg yolk.

Mushrooms and avocados also contain vitamin D – but in a form that the body can only poorly absorb. You would actually need to consume large amounts of these foods to even get close to the the lowest recommended daily requirement. For the 600 International Units recommended by the National Institutes of Health – that is, 20 microgrammes, you would need for example 2,400 grammes of mushrooms, four kilos of beef liver, four kilos of butter or 80 eggs.^[2]

In summary, with food alone, it is not possible to meet your daily requirement for vitamin D. Our bodies have to produce the largest proportion of vitamin D ourselves – and this simply does not work without sunlight.

Does vitamin D affect vitamin K?

Vitamin K is thought to have a similar protective effect to vitamin D. Its role is to primarily prevent and treat bone and vascular diseases. Vitamin K1 is found, for instance, in green vegetables, while vitamin K2 is produced by our gut microbiome. How much vitamin K we need exactly has not yet been fully researched^[41].

Again and again it has been written that when consuming vitamin D, you may find that this leads to low vitamin K levels, since both vitamins are involved in bone formation and mutually influence one another. However, this idea has not been scientifically proven.^[40] Medical experts currently recommend taking supplements containing both vitamin D and vitamin K to specifically treat osteoporosis and prevent bone fractures occurring in older people.^[41–43]

Vitamin D deficiency symptoms and treatment – at a glance What is vitamin D? Vitamin D is both a fat-soluble vitamin and a hormone at the same time. It is involved in many processes in the body, including bone metabolism, muscle function, the immune system and vascular protection. Where do people get vitamin D from? Our body produces 80 to 90 per cent of vitamin D all by itself – but to do this, it needs the UVB radiation from sunlight. To maintain our vitamin D levels, we must expose our face, hands and arms to the sun three times a week for 10 to 20 minutes during the summer months. The remaining 10 to 20 per cent we get from our diet – that is, from fatty fish, eggs, dairy products and edible mushrooms. Who is most affected by vitamin D deficiency? Around one billion people across the world are not adequately supplied with vitamin D. The risk groups include the elderly, pregnant women, people with darker skin types and people who hardly ever go outdoors or cover most of their body when doing so. What are typical long-term vitamin D3 deficiency symptoms? Vitamin D deficiency – or vitamin D3 deficiency – can have a particularly negative impact on bone health where it may promote osteomalacia and osteoporosis. Other illnesses associated with a deficiency include depression, cardiovascular disease, hair loss, skin diseases, and migraines. How do I check vitamin D levels? Using a blood test, you can determine the concentration of 25-(OH)-D in your blood. This is the most meaningful parameter that describes your supply of vitamin D. You can measure your vitamin D levels with an at-home self-test. Most scientific sources recommend levels of at least 30 nanogrammes per millilitre of blood. How can I treat vitamin D deficiency? If you have a vitamin D deficiency, it is difficult to counteract it with diet and sunbathing alone, especially during autumn and winter. Dietary supplements are more effective. A daily dose of 1,000 to 2,000 International Units (IU) is recommended to maintain good vitamin D levels. To correct a deficiency, higher doses may be useful.

Sources

[1]     Parva N. R., Tadepalli S., Singh P., et al. “Prevalence of Vitamin D Deficiency and Associated Risk Factors in the US Population (2011-2012),” Cureus, 2018; 10(6):e2741, June 5, 2018, doi:10.7759/cureus.2741

[2]      Kasper, H., Burghardt, W. Nutritional medicine and dietetics, Elsevier, Urban & Fischer, Munich (2014)

[3]      Skypala, I. “Adverse food reactions--an emerging issue for adults,” J. Am. Diet. Assoc. 111, 2011, pp. 1877–1891.

[4]      Roitt, I. M., Brostoff, J., Male, D. K. eds: Kurzes Lehrbuch der Immunologie. Thieme, Stuttgart (1995)

[5]      “Food Allergy,” American College of Allergy, Asthma & Immunology, available at http://acaai.org/allergies/types/food-allergy

[6]     “Vitamin D,” Mayo Clinic, available at https://www.mayoclinic.org/drugs-supplements-vitamin-d/art-20363792

[7]      Graham-Rowe, D. “Lifestyle: When allergies go west,” Nature, 479, 2011, S2–S4.

[8]      Björkstén, B. “Genetic and environmental risk factors for the development of food allergy,” Curr. Opin. Allergy Clin. Immunol. 5, 2005, pp. 249–253.

[9]      Naleway, A. L. “Asthma and Atopy in Rural Children: Is Farming Protective?” Clin. Med. Res. 2, 2004, pp. 5–12.

[10]      Sepp, E., Julge, K., Vasar, M., Naaber, P., Björksten, B., Mikelsaar, M. “Intestinal microflora of Estonian and Swedish infants,” Acta Paediatr. Oslo Nor. 1992, 86, pp. 956–961 (1997).

[11]      “S3-Leitlinie Allergieprävention - Update 2014,” Leitlinie der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI) und der Deutschen Gesellschaft für Kinder- und Jugendmedizin (DGKJ)

[12]      Molloy, J., Allen, K., Collier, F., Tang, M. L. K., Ward, A. C., Vuillermin, P. “The Potential Link between Gut Microbiota and IgE-Mediated Food Allergy in Early Life,” Int. J. Environ. Res. Public. Health. 10, 2013, pp. 7235–7256.

[13]      Nwaru, B. I. et al., “EAACI Food Allergy and Anaphylaxis Guidelines Group: The epidemiology of food allergy in Europe: a systematic review and meta-analysis,” Allergy, 69, 2014, pp. 62–75

[14]      Boyce, J. A. et al., “NIAID-sponsored Expert Panel: Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-Sponsored Expert Panel Report,” Nutr. Burbank Los Angel. Cty. Calif. 27, 2011, pp. 253–267

[15]      “Guideline Management of IgE Mediated Food Allergies S2k LL,” Allergo Journal, 11-2015

[16]      Ho, M. H.-K., Wong, W. H.-S., Chang, C. “Clinical spectrum of food allergies: a comprehensive review,” Clin. Rev. Allergy Immunol. vol. 46, 2014, pp. 225–240

[17]      RKI - Number of the Month - April 2017: Allergies

[18]      Burks, A. W., Tang, M., Sicherer, S., Muraro, A., Eigenmann, P. A., Ebisawa, M., Fiocchi, A., Chiang, W., Beyer, K., Wood, R., Hourihane, J., Jones, S. M., Lack, G., Sampson, H. A. “ICON: food allergy,” J. Allergy Clin. Immunol. vol. 129, 2012, pp. 906–920

[19]      McGowan, E. C., Keet, C. A. “Prevalence of self-reported food allergy in the National Health and Nutrition Examination Survey (NHANES) 2007-2010,” J. Allergy Clin. Immunol. vol. 132, 2013, pp. 1216–1219.e5

[20]      Sicherer, S. H. “Clinical implications of cross-reactive food allergens,” J. Allergy Clin. Immunol. vol. 108, 2001, pp. 881–890

[21]      Sampson, H. A. et al. “Food allergy: a practice parameter update-2014,” J. Allergy Clin. Immunol. vol. 134, 2014, pp. 1016–1025.e43

[22]      Nowak-Wegrzyn, A., Fiocchi, A. “Rare, medium, or well done? The effect of heating and food matrix on food protein allergenicity.” Curr. Opin. Allergy Clin. Immunol. 9, 2009, pp. 234–237

[23]      Nowak-Wegrzyn, A. et al. “Tolerance to extensively heated milk in children with cow’s milk allergy,” J. Allergy Clin. Immunol. vol. 122, 2008, pp. 342–347, 347.e1–2

[24]      Osborne, N. J. et al., “HealthNuts Investigators: Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants,” J. Allergy Clin. Immunol. vol. 127, 2011, pp. 668-676.e1–2

[25]      Peters, R. L., Allen, K. J., Dharmage, S. C., Koplin, J. J., Dang, T., Tilbrook, K. P., Lowe, A., Tang, M. L. K., Gurrin, L. C., “HealthNuts Study: Natural history of peanut allergy and predictors of resolution in the first 4 years of life: A population-based assessment.” J. Allergy Clin. Immunol. vol. 135, 2015, pp. 1257–1266.e1–2

[26]      Bock, S. A., Muñoz-Furlong, A., Sampson, H. A. “Fatalities due to anaphylactic reactions to foods,” J. Allergy Clin. Immunol. vol. 107, 2001, pp. 191–193.

[27]      Bock, S. A., Muñoz-Furlong, A., Sampson, H. A. “Further fatalities caused by anaphylactic reactions to food,” 2001-2006, J. Allergy Clin. Immunol. vol. 119, 2007, pp. 1016–1018

[28]      Chen, J. L., Bahna, S. L. “Spice allergy,” Ann. Allergy Asthma Immunol. Off. Publ. Am. Coll. Allergy Asthma Immunol. vol. 107, 2011, pp. 191-199; quiz 199, 265

[29]      Muraro, A. et al., “EAACI Food Allergy and Anaphylaxis Guidelines Group: EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy,” Allergy, 2014, vol. 69, pp. 590–601

[30]      Leitlinie_Management_IgE-vermittelter_Nahrungsmittelallergien-S2k

[31]      Worm, M., et al. “Food allergies resulting from immunological cross-reactivity with inhalant allergens,” Allergo J. Int. vol. 23, 2014, pp. 1–16

[32]      Beaudouin, E., Renaudin, J. M., Morisset, M., Codreanu, F., Kanny, G., Moneret-Vautrin, D. A. “Food-dependent exercise-induced anaphylaxis--update and current data,” Eur. Ann. Allergy Clin. Immunol. vol. 38, 2006, pp. 45–51

[33]      Patterson, A. M., Yildiz, V. O., Klatt, M. D., Malarkey, W. B. “Perceived stress predicts allergy flares,” Ann. Allergy Asthma Immunol. Off. Publ. Am. Coll. Allergy Asthma Immunol. vol. 112, 2014, pp. 317–321.

[34]      Niggemann, B., Beyer, K. “Factors augmenting allergic reactions,” Allergy, vol. 69, pp. 1582–1587, 2014.

[35]      Werfel, T., Breuer, K. “Role of food allergy in atopic dermatitis,” Curr. Opin. Allergy Clin. Immunol. vol. 4, 2004, pp. 379–385.

[36]      Ellman, L. K., Chatchatee, P., Sicherer, S. H., Sampson, H. A. “Food hypersensitivity in two groups of children and young adults with atopic dermatitis evaluated a decade apart,” Pediatr. Allergy Immunol. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol. vol. 13, 2002, pp. 295–298.

[37]      Atherton, D. J. et al. “A double-blind controlled crossover trial of an antigen-avoidance diet in atopic eczema,” Lancet Lond. Engl. 1, 1978, pp. 401–403.

[38]      “Review article: the aetiology, diagnosis, mechanisms and clinical evidence for food intolerance,” Alimentary Pharmacology & Therapeutics, Lomer 2014.

[39]      Turnbull, J. L., Adams, H. N., Gorard, D. A. “Review article: the diagnosis and management of food allergy and food intolerances,” Aliment. Pharmacol. Ther., vol. 41, 2015, pp. 3–25.

[40]      Shakoor, Z., et al. “Prevalence of IgG-mediated food intolerance among patients with allergic symptoms,” Ann. Saudi Med. vol. 36, 2016, pp. 386–390.

[41]      Steeb, D. med S. Food intolerance: How to test yourself step by step to the correct diagnosis. Over 60 new recipes - also for multiple intolerances, Schlütersche, 2015.

[42]      Zhang, Y., Chen, Y., Zhao, A., Li, H., Mu, Z., Zhang, Y., Wang, P. “Prevalence of self-reported food allergy and food intolerance and their associated factors in 3 - 12 year-old children in 9 areas in China,” Wei Sheng Yan Jiu. vol. 44, 2015, pp. 226–231.

[43]      Turnbull, J. L., Adams, H. N., Gorard, D. A. “Review article: the diagnosis and management of food allergy and food intolerances,” Aliment. Pharmacol. Amp Ther. vol. 41, 2015, pp. 3–25.

[44]      Authority, N. F., “Allergy and intolerance,” available at /foodsafetyandyou/life-events-and-food/allergy-and-intolerance.

[45]      “Lactose - Fructose - Sorbitol,” DAAB, available at http://www.daab.de/lebensmittel-allergietag/laktose-fruktose-sorbit/.

[46]      Berni Canani, R., Pezzella, V., Amoroso, A., Cozzolino, T., Di Scala, C., Passariello, A. “Diagnosing and Treating Intolerance to Carbohydrates in Children,” Nutrients, vol. 8, p. 157, 2016.

[47]      “Food intolerance, National Health Service,” reviewed August 12, 2019, available at https://www.nhs.uk/conditions/food-intolerance/.

[48]      Cuomo, A., Giordano, N. Goracci, A. and Fagiolini, A. “Depression and Vitamin D Deficiency: Causality, Assessment, and Clinical Practice Implications,” available at https://www.jneuropsychiatry.org/peer-review/depression-and-vitamin-d-deficiency-causality-assessment-and-clinical-practice-implications-12051.html

[49]      Majid, M. S., Ahmad, H. S., Bizhan, H., Hosein, H. Z. M., Mohammad, A. “The effect of vitamin D supplement on the score and quality of sleep in 20-50 year-old people with sleep disorders compared with control group,” available at https://pubmed.ncbi.nlm.nih.gov/28475473/#affiliation-1.

[50]      Almohanna, H. M., Ahmed, A. A., Tsatalis, J. P., and Tosti, A. “The Role of Vitamins and Minerals in Hair Loss: A Review,” available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380979/.

[51]      Malhotra, R. “Understanding migraine: Potential role of neurogenic inflammation,” available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888678/.

[52]      Yin, K., Agrawal, D. K. “Vitamin D and inflammatory diseases,” available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070857/.

[53]      Wadhwa B., Relhan V., Goel K., Kochhar A. M., Garg V. K. “Vitamin D and skin diseases: A review,” Indian J Dermatol Venereol Leprol, July–August 2015, vol. 81(4), pp. 344–355, doi: 10.4103/0378-6323.159928. PMID: 26144849.

[54]      Palmer D. J. “Vitamin D and the Development of Atopic Eczema,” Journal of clinical medicine, vol. 4(5), 2015, pp. 1036–1050. https://doi.org/10.3390/jcm4051036.

[55]      AlGhamdi, K., Kumar, A., Moussa, N. “The role of vitamin D in melanogenesis with an emphasis on vitiligo,” Indian journal of dermatology, venereology and leprology, vol. 79(6), 2013, pp. 750–758, available at https://doi.org/10.4103/0378-6323.120720.

[56]      Kheiri, B., Abdalla, A., Osman, M., Ahmed, S., Hassan, M., Bachuwa, G. “Vitamin D deficiency and risk of cardiovascular diseases: a narrative review,” Clinical hypertension, 24, 9, 2018, available at https://doi.org/10.1186/s40885-018-0094-4.

[57]      Garland, C. F., Garland, F. C., Gorham, E. D., Lipkin, M., Newmark, H., Mohr, S. B., Holick, M. F. “The role of vitamin D in cancer prevention,” American journal of public health, vol. 96(2), 2006, pp. 252–261, https://doi.org/10.2105/AJPH.2004.045260.

[58]      Amin H. A., “No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data,” BMJ Nutrition, Prevention & Health, January 7, 2021, doi: 10.1136/bmjnph-2020-000151.

[59]      “Vitamin D,” Britannica, available at https://www.britannica.com/science/vitamin-D, accessed on August 11, 2021.

[60]      Crowe, Francesca L et al. ‘Trends in the incidence of testing for vitamin D deficiency in primary care in the UK: a retrospective analysis of The Health Improvement Network (THIN), 2005–2015.’ BMJ open, vol. 9,6 e028355. 4 Jun. 2019, doi:10.1136/bmjopen-2018-028355