Vitamin D deficiency symptoms in Malta: testing, causes, and what primary care reveals
What low Vitamin D can feel like, why it happens even in sunny Malta, and what a 2021 audit across nine primary health centres shows about when doctors test.
Dr Shehan Wijesingha MD, M.TCM, BMedSci, DipAP, CPT
Key takeaways
- The most common Vitamin D deficiency symptoms are often non-specific. Fatigue, low mood, muscle weakness, bone pain, vague aches, recurrent infections, and slower recovery from illness are commonly reported. Many people have no obvious symptoms at all.
- Malta’s sunlight does not guarantee healthy Vitamin D levels. Indoor lifestyles, age, skin pigmentation, sun avoidance, sunscreen use, air pollution, clothing habits, malabsorption, and some medications can all reduce Vitamin D status.
- A blood test is the only reliable way to know. Symptoms can raise suspicion, but they cannot confirm a true deficiency. The standard test measures 25-hydroxyvitamin D in the blood.
- Vitamin D testing in Malta’s primary care broadly follows international convention. In this audit, the most common reasons for testing were metabolic bone disease, patient request, and follow-up of previously low Vitamin D levels.
- The most revealing finding was what doctors did not mention. Across all nine centres, no doctor mentioned cancer, neurological disease, cardiorespiratory disease, autoimmune disease, or pathology associated with thrombosis as a reason to test, even though the wider literature links low Vitamin D status to these areas with varying strength of evidence.
Vitamin D deficiency symptoms
The symptoms of Vitamin D deficiency can be easy to miss because they are often vague. The most commonly reported symptoms include fatigue, low mood, muscle weakness, vague muscle or joint pain, bone pain or tenderness, recurrent infections, and slower recovery from illness.
In more severe deficiency, Vitamin D deficiency can cause rickets in children and osteomalacia in adults. These are clearer medical conditions involving bone pain, muscle weakness, walking difficulty, deformity in children, and increased fracture risk.
Most people do not present in this textbook way. In real clinical practice, the presentation is often much less dramatic. Someone may feel tired, low, achy, run down, or slower to recover from illness. Another person may have no obvious symptoms at all.
This is why symptoms are useful, but limited. They can raise suspicion. They cannot confirm a true deficiency. The only way to know is to measure 25-hydroxyvitamin D in the blood.
Vitamin D is usually thought of as a bone vitamin. That is true, but incomplete.
Vitamin D is one of the most researched nutrients and hormones in medicine. In routine practice, it is still often approached mainly through calcium, parathyroid function, rickets, osteomalacia, osteoporosis, and fractures.
Whilst those links matter, the bigger picture matters too.
The scientific literature connects Vitamin D status with immune function, infection risk, cardiovascular disease, respiratory disease, neurological disease, mental health, autoimmunity, pregnancy outcomes, gut barrier function, liver disease, kidney disease, and mechanisms related to thrombosis and vascular inflammation.
I believe Vitamin D belongs inside proper clinical reasoning without exaggerated claims. In the right context, it can be a meaningful part of the wider clinical picture.
That is why this article does two things. First, it answers the practical question most people have: what are the symptoms of Vitamin D deficiency, and how do you know if you have it? Second, it explains what an audit across Malta’s nine primary health centres revealed about how doctors actually decide when to test.
Why Vitamin D matters
Vitamin D is likely to be one of the oldest, if not the oldest hormone that has existed on earth. Throughout evolution, exposure to sunlight and the photosynthesis of Vitamin D in the skin has been crucial for the evolution of land vertebrates, with overexposure to sunlight not resulting in Vitamin D intoxication.
It is estimated that exposure in a bathing suit to 1 minimal erythemal dose, meaning the amount of UV radiation needed to produce minimal erythema, sunburn, or redness caused by capillary engorgement1, is equivalent to ingesting between 10,000 and 25,000 IU of Vitamin D within a few hours after exposure2.
Approximately 3% of the human genome is directly or indirectly regulated by the Vitamin D endocrine system. Vitamin D insufficiency has also been described as an independent risk factor for total mortality in the general population, affecting almost 50% of the global population.
This can happen even in sunny countries.
Modern life has reduced exposure to sunlight, which is required to induce Vitamin D production in the skin. Air pollution3, skin pigmentation2, sun avoidance, sunscreen application, cultural habits, and clothing practices can all reduce Vitamin D production.
Age matters too. Elderly people regularly exposed to sunlight produce around 75% less cutaneous Vitamin D3 than young adults4.
Food is also a limited source. Although wild caught salmon has been observed to contain between 75% and 90% more Vitamin D3 than farmed salmon, very few foods naturally contain Vitamin D in meaningful amounts, and the content is highly variable2.
People can live in sunny climates and still be Vitamin D deficient5. In my clinical experience working in Malta, the large majority of people I test for Vitamin D have typically been deficient, despite Malta being a very sunny country compared with much of the world.
Severe Vitamin D deficiency, rickets, and osteomalacia
Severe Vitamin D deficiency in children causes rickets. Severe deficiency in adults causes osteomalacia.
The clinical features of rickets, as set out in UK primary care guidelines for Vitamin D deficiency6, 7, include poor growth, delayed fontanelle closure, delayed walking or a waddling gait, tender or swollen joints, deformed bones such as bow legs or knock knees, bone pain or tenderness, muscle pain or proximal myopathy, delayed eruption of teeth, and symptoms of low calcium such as carpopedal spasm, tetany, seizures, or irritability.
For osteomalacia, the same guidelines list gradual onset and persistent bone pain without preceding mechanical injury, often in the back, ribs, or lower limb, fragility fracture, proximal muscle weakness, difficulty with stairs, getting up off the floor, standing after sitting in a low chair, waddling gait, muscle pain, and symptoms of low calcium.
Wirral University Teaching Hospital guidelines for treatment of Vitamin D deficiency in adults list muscle pain, proximal muscle weakness, and rib, hip, pelvis, thigh and foot pain as clinical features of Vitamin D deficiency8.
This is the severe end of the spectrum. Most people with Vitamin D deficiency do not present in this textbook way. They may have vague symptoms, or no symptoms at all.
The symptoms most patients notice are not specific to Vitamin D. Fatigue, low mood, muscle pain, poor recovery, and recurrent infections can have many causes. Vitamin D deficiency may be one contributor, one marker of a wider problem, or sometimes not relevant.
After having conducted this research, I do believe there is a reasonable argument for Vitamin D to be included more often as part of routine blood testing ordered by doctors. This is broader than some of the guidelines quoted below, and I will explain why I think this argument deserves to be considered.
What this audit looked at
Between 17 May 2021 and 30 May 2021, a questionnaire was distributed to doctors working across all nine health centres in Malta: Mosta, Birkirkara, Rabat, Gzira, Floriana, Qormi, Conspicua, Kirkop and Paola.
Each doctor was asked, in their own words:
For what reason(s) do you currently order the Vitamin D blood test for your patients?
Doctors ranged from Foundation Year doctors to qualified GPs. The aim was to understand when Vitamin D tests were being ordered by physicians in Malta, and whether this was the right approach.
What the audit found
During the two weeks in which this data was collected, there were 160 doctors in total working in all 9 health centres in Malta. 91 of those doctors answered the question for this audit, equating to 57% of primary care doctors during this period.
The indications for which doctors in Malta’s primary health centres ordered Vitamin D tests, in descending order of frequency, were:
- metabolic bone disease (63 doctors)
- patient request (55)
- patients taking Vitamin D supplements or with previously low Vitamin D levels (29)
- reduced intake or malabsorption (24)
- calcium or parathyroid disease (19)
- fatigue or lethargy (14)
- elderly patients (12)
- reduced sunlight exposure (12)
- routine testing (11)
- infection or to improve immunity (11)
- kidney disease (6)
- depression or low mood (5)
- liver disease (4)
Under metabolic bone disease, doctors stated they would order Vitamin D tests for patients who had or were at risk of osteopenia, osteoporosis, osteomalacia or bone disease.
The fourth most common area was malabsorption, such as coeliac disease and inflammatory bowel disease, and reduced intake, including restrictive diets and malnourishment. The fifth most common indication was calcium or parathyroid disease.
The most important finding may be what was not mentioned.
Not a single doctor working in Malta’s primary health centres mentioned cancer, neurological disease, cardiorespiratory disease, autoimmune disease, or pathology associated with thrombosis as an indication to order Vitamin D tests.
This approach by doctors in Malta broadly reflects international testing guidelines. I would argue, however, that the real question is whether this is genuinely the correct approach, not just in Malta, but worldwide.
Vitamin D and bone health
The best-known role of Vitamin D is in bone health.
Vitamin D is an essential precursor to calcitriol, the major biologically active hormonal form of Vitamin D. Calcitriol binds to the Vitamin D receptor (VDR), which can activate or suppress transcription of thousands of VDR sites identified to date.
Vitamin D can be derived from plants as Vitamin D2, ergocalciferol, from animals as Vitamin D3, cholecalciferol, or from sunlight, where the skin uses ultraviolet B rays to synthesise Vitamin D3 from 7-dehydrocholesterol.
Vitamin D3 is then activated first in the liver to 25(OH)D, with CYP2R1 appearing to be the most important enzyme. The enzyme 1-α-hydroxylase (CYP27B1) appears to be responsible for the subsequent 1α-hydroxylation to calcitriol in the kidney9.
Vitamin D is essential in serum calcium homeostasis by increasing intestinal calcium absorption, increasing renal calcium reabsorption, and stimulating calcium release from bone through raised osteoclast activity10.
This is why Vitamin D testing is so strongly linked to rickets, osteomalacia, osteoporosis, fragility fracture, calcium disturbance, and parathyroid disease.
A randomised controlled trial has shown that Vitamin D supplementation can increase bone mineral density and rectify abnormalities caused by osteomalacia11. Meta-analyses have also found Vitamin D supplementation to improve bone mineral density in deficient children and adolescents12, reduce the risk of falls in elderly patients13–15, and reduce hip fracture risk in middle-aged to older adults when combined with calcium16.
Testing Vitamin D in suspected bone disease, falls risk, fragility fracture, rickets, osteomalacia, osteoporosis, calcium disturbance, or parathyroid-related problems is appropriate. The more important question is whether the thinking should genuinely stop there.
Vitamin D beyond bone health
The evidence becomes more nuanced outside bone health, but I think a bone-only view is too narrow when considering the importance of Vitamin D.
Calcitriol exerts anticancer properties through anti-proliferative and pro-apoptotic actions on various malignant cells; suppression of tumour angiogenesis, invasion, and metastasis; increased DNA repair, antioxidant protection, and immunomodulation17; direct and indirect inhibition of aromatase transcription, the enzyme that catalyses oestrogen synthesis in breast cancer; anti-inflammatory effects through prostaglandin suppression and inhibition of pro-inflammatory cytokine production through p38 stress kinase signalling inhibition18; and modulation of cellular growth and development19.
Meta-analyses have found a beneficial effect of Vitamin D supplementation in reducing cancer-related mortality20, 21, as well as correlations in lung cancer22–24, breast cancer25, 26, ovarian cancer27, 28, colorectal cancer29–32, pancreatic cancer33, prostate cancer34–36, malignant melanoma37, 38, and basal cell carcinoma39.
Infection and immunity
Vitamin D3, like melatonin, exerts an antioxidant effect40. Immune cells express enzymes which convert Vitamin D into calcitriol, which then modulates the immune system1. This happens through effects on immune cell growth, differentiation, antimicrobial peptides41, and gene expression in Vitamin D responsive tissues42.
This may help explain the seasonal stimulus that profoundly increases the pathogenesis of influenza in winter months43, and the literature linking Vitamin D deficiency with mortality in the critically ill44, COVID-1945–49, and more severe respiratory50–54, urinary55, and gastrointestinal56–59 infections, with Vitamin D supplementation being found to be protective in several analyses60–68.
Cardiorespiratory and metabolic health
Two meta-analyses69, 70 and a systematic review71 have shown an association between low circulating 25(OH)D and elevated risk of hypertension. Some analyses suggest Vitamin D supplementation may reduce blood pressure in hypertensive individuals71–73, while others do not support a clear effect70.
Similar mixed evidence exists for cardiovascular outcomes. One meta-analysis found a reduced risk of cardiac failure through Vitamin D supplementation in patients with low 25(OH)D, but no association with myocardial infarction and stroke74. Other meta-analyses found no significant reduction in cardiovascular risk or major cardiovascular events75, 76, even though low 25(OH)D has been associated with increased cardiovascular risk77.
In respiratory disease, the evidence is more clinically suggestive. Meta-analyses have linked sufficient Vitamin D levels with better lung function in asthma78, and Vitamin D supplementation with reduced asthma exacerbations in children and adults, especially where insufficiency is present79–82. COPD findings are mixed, with some analyses linking deficiency to severity and others suggesting supplementation may reduce exacerbations83–86.
Neurological and mental health
Vitamin D has also been studied in the nervous system.
Meta-analyses have found that 25(OH)D deficiency can increase the risk of stroke, especially ischaemic stroke87, 88. Reduced 25(OH)D has been found in patients with reduced cognition and Alzheimer’s disease89–91, and low concentrations have been linked with Parkinson’s disease, with one meta-analysis finding a twofold increased risk in patients with Vitamin D deficiency92.
The link with multiple sclerosis is less definitive. Some studies associate low Vitamin D with increased risk93, while others find no clear association with disability score, relapse rate, prevalence, or mortality94–96.
In mental health, systematic reviews and meta-analyses have associated low Vitamin D with depression97, 98, post-partum depression99, 100, post-partum anxiety101, and psychotic disorders, particularly schizophrenia102. Some reviews suggest supplementation may improve outcomes in depression and anxiety, especially in Vitamin D deficient patients and those with major depressive disorder103–105.
Mental health and neurological conditions need proper assessment and appropriate care. Low Vitamin D status can still sit inside the wider biological picture of mood, cognition, oxidative stress, inflammation, sleep, and nervous system function.
Liver, kidney, gut and pregnancy
Several meta-analyses have found lower Vitamin D levels in non-alcoholic fatty liver disease (NAFLD)106–108, although trial evidence on supplementation is mixed109–111. In liver cirrhosis, Vitamin D deficiency has been linked to disease severity and mortality112.
In chronic kidney disease, meta-analyses suggest Vitamin D supplementation can improve biochemical endpoints, reduce PTH without raising calcium or phosphate, and may reduce all-cause and cardiovascular mortality, especially in secondary hyperparathyroidism113–115.
In inflammatory bowel disease, patients have been shown to have 64% higher odds of Vitamin D deficiency than controls116. Vitamin D deficiency has also been associated with compromised gut microbiome composition117, and Vitamin D supplementation has been linked to improved gut microbiome composition, reduced Helicobacter pylori, and reduced proteobacteria in the gut mucosa118.
In pregnancy, severe Vitamin D deficiency has been associated with early embryonic development and spontaneous pregnancy loss119, and low circulating Vitamin D has been linked with pre-eclampsia, gestational diabetes, pre-term birth and SGA, meaning small gestational age120. Vitamin D supplementation during pregnancy has been associated with reduced risk of preterm birth121.
How Vitamin D may affect so many systems
Vitamin D appears across so many areas of the literature because it acts as a hormone as well as a nutrient.
Vitamin D becomes calcitriol, which binds to the Vitamin D receptor and influences gene expression9. From there, its effects can extend into calcium homeostasis, immune regulation, intestinal barrier function, inflammation, vascular biology, coagulation pathways, blood pressure regulation, and the nervous system.
Some of the mechanisms described in the literature include:
- Calcium and bone homeostasis. Vitamin D increases intestinal calcium absorption, renal calcium reabsorption, and calcium release from bone through raised osteoclast activity10.
- Immune homeostasis. Calcitriol modulates monocytes, macrophages, dendritic cells, T-lymphocytes and B-lymphocytes, and influences cytokine production and Vitamin D receptor expression41, 42.
- Intestinal barrier function. Vitamin D and its receptor help regulate antimicrobial peptides such as cathelicidin122, 123, support tight junction proteins such as occludin, claudin, vinculin, ZO-1 and ZO-2124, and help maintain epithelial barrier integrity.
- Autoimmunity protection. Calcitriol has been shown to inhibit Th1 cells and reduce IL-2 and interferon-γ in CD4+ cells in vitro, mechanisms relevant to autoimmune conditions such as rheumatoid arthritis, multiple sclerosis, type 1 diabetes and inflammatory bowel disease125.
- Antithrombotic homeostasis. Calcitriol may influence nitric oxide, tissue factor, tissue factor pathway inhibitor, antithrombin, thrombomodulin, platelet aggregation, and endothelial inflammation126–130.
- Blood pressure regulation. Vitamin D may inhibit renin transcription through interaction with CREB, meaning cAMP-response element binding protein, affecting sympathetic drive, sodium reabsorption, vasoconstriction, aldosterone and water retention131.
- Neuroprotection. Vitamin D receptors and 1α-hydroxylase are found in brain areas including the hippocampus, dentate gyrus, hypothalamus and substantia nigra132, 133. Vitamin D has been linked with nerve growth factor, neurotrophins, glial-derived neurotrophic factor, amyloid plaque clearance, dopaminergic neuron protection, glutathione, and antioxidation134–143.
- Cytoprotective and anti-inflammatory action. Vitamin D induces lipoxygenase expression and activity144, and has been linked with vascular endothelial function145. It can also upregulate heme oxygenase-1 (HO-1), a cytoprotective enzyme produced under stress and inflammation, in respiratory146 and intestinal147 tissue.
All of the above are reasons I believe Vitamin D should not be reduced to bones alone.
When guidelines recommend testing
The harder question may be when Vitamin D should be tested.
International guidelines generally do not recommend testing everyone. They recommend testing when there are symptoms, risk factors, or a clinical reason why the result would change management.
United Kingdom
NICE, UK recommend not routinely testing Vitamin D status unless the patient has symptoms of deficiency, is at particularly high risk of deficiency, or there is a clinical reason to do so, such as osteomalacia or a fall148.
The UK’s National Osteoporosis Society Vitamin D Guidelines149 recommend serum 25(OH)D measurement for patients with musculoskeletal symptoms that could be attributed to Vitamin D deficiency, where correcting deficiency before treatment such as bisphosphonates would be appropriate, or in bone diseases such as confirmed osteomalacia and osteoporosis that may improve with Vitamin D treatment.
North Lincolnshire6, Derbyshire7, and Wirral University Teaching Hospital guidance8 also focus mainly on symptoms of rickets, osteomalacia, and clinical features such as muscle pain, proximal muscle weakness, and rib, hip, pelvis, thigh and foot pain.
United States
The US Preventive Services Task Force150 concluded that evidence on screening for Vitamin D deficiency to improve health outcomes is insufficient.
The Endocrine Society151 recommends testing patients at risk, including those with osteomalacia, osteoporosis or rickets; chronic kidney disease or hepatic failure; malabsorption syndromes; parathyroid disorders; certain medications including anti-seizure medications, glucocorticoids, AIDS medications, antifungals and cholestyramine; African American and Hispanic children and adults; pregnant and lactating women; older adults with falls or non-traumatic fractures; obesity; granuloma forming disorders; and some lymphomas.
Canada and Australia
Ontario guidelines152 state that routine Vitamin D testing is not warranted in the average at-risk population, but may be clinically valuable in renal or liver disease, osteomalacia, osteopenia, osteoporosis, rickets, malabsorption, calcium, phosphate or parathyroid disorders, medication-related risk, unexplained high alkaline phosphatase, or possible Vitamin D toxicosis.
Australian guidance from the Royal College of Pathologists of Australasia153 recommends against routine screening of healthy infants, children and adults, including pregnant women. Indications include signs, symptoms or planned treatment of osteoporosis or osteomalacia; abnormal alkaline phosphatase with otherwise normal liver function tests; parathyroid, calcium or phosphate disorders; malabsorption; chronic renal failure; renal transplant; deeply pigmented skin; severe lack of sun exposure; and medications known to reduce 25(OH)D levels.
The shared principle seems clear: do not test everyone casually, but test when there is a good reason. That is understandable. The question is whether these guidelines are genuinely optimal based on the current scientific literature.
What this might mean for Malta
Malta does not currently have national guidelines for when to test for Vitamin D. The results of this audit are overall relatively consistent with guidelines from the UK, US, Canada and Australia.
Whilst it is reassuring that Vitamin D testing in Malta’s primary care broadly reflects international convention, it also raises an important question.
This audit drew on a literature review of over 300 studies including over 130 meta-analyses and systematic reviews. International guidelines and recommendations for Vitamin D testing appear limited by the goals of treatment, which often focus primarily on bone health.
Emphasis in undergraduate and postgraduate medical exams on the relation of Vitamin D to calcium and parathyroid homeostasis and bony pathology, combined with reduced emphasis on the biochemical and clinical effects of Vitamin D and supplementation on non-skeletal conditions, may be one reason why most doctors in Malta’s primary health care system may see metabolic bone disorders and calcium or parathyroid disorders as the most important and often the only proper indication for Vitamin D testing.
The second largest indication in this audit was patient request. Some doctors expressed concern about this, attributing it to the media, internet or social media. Others interpreted it as increased patient awareness.
Both concerns can be true.
There is a risk of overdiagnosis and overtreatment. In Australia, Vitamin D testing has been observed to increase by 59% per year, consuming a substantial portion of the annual health budget. The University of Sydney has reported an increased trend of overdiagnosis and overtreatment of Vitamin D deficiency154, with one study finding that limiting 25(OH)D testing to 3 tests annually per individual could save over A$20 million over four and a half years155.
There is also a risk of under-recognition, especially when someone has chronic symptoms, risk factors, low sun exposure, malabsorption, medication-related risk, recurrent infections, fatigue, pain, low mood, or multi-system illness.
Medication interactions worth knowing about
If you take medication regularly, there are a few interactions worth being aware of when considering Vitamin D testing or supplementation, or when supplements such as magnesium and Vitamin K2 are being considered alongside.
Do not stop a prescribed medication because of anything in this section. This information is here to help you become more informed and to support a better conversation with your prescribing clinician.
Proton pump inhibitors and other acid-lowering medications. Long-term use of PPIs, such as omeprazole, esomeprazole, lansoprazole and pantoprazole, and H2-receptor antagonists can change gastric acidity and has been associated with reduced calcium and Vitamin D absorption and with adverse bone outcomes in some studies, although the picture is not uniform.
Thiazide diuretics. Thiazides, such as bendroflumethiazide and indapamide, reduce urinary calcium excretion, which raises serum calcium. In a patient also taking Vitamin D, particularly at higher doses, the combination can occasionally produce hypercalcaemia.
Anticoagulants, particularly warfarin. Vitamin K2 is sometimes recommended alongside Vitamin D in the context of bone and vascular health. Vitamin K2 directly antagonises the action of warfarin. Patients on warfarin should not take Vitamin K2 supplements without explicit guidance from their prescribing clinician.
Glucocorticoids. Long-term oral glucocorticoid therapy, such as prednisolone, is associated with reduced Vitamin D activity, accelerated bone loss, and increased fracture risk.
Some antiepileptic medications. Older antiepileptics including phenytoin, phenobarbital, carbamazepine and primidone induce hepatic enzymes that accelerate Vitamin D catabolism, and have been associated with lower Vitamin D status and reduced bone density on long-term use.
Other medication and absorption issues. Antiretrovirals, bile acid sequestrants such as cholestyramine, weight-loss medications such as orlistat, and bariatric surgery are all recognised risk factors for reduced Vitamin D absorption or status.
This is not an exhaustive list. It is a reminder that supplements interact with medication, and that Vitamin D supplementation should be considered in the context of a full medication review by an informed physician.
What this means for chronic, unresolved cases
The clinical context in which Vitamin D status most often becomes relevant is the chronic, unresolved presentation.
This is the person who has been unwell for months or years, whose tests have been broadly normal, and whose symptoms span multiple systems.
In that population, Vitamin D status can be one of several variables that is easy to overlook and easy to check.
I do not think Vitamin D is often the single answer. It is more often one of several variables that may help explain why someone has not been responding to single-system treatment.
In that wider picture, Vitamin D status can matter alongside chronic fatigue, persistent low mood and anxiety, widespread musculoskeletal pain including patterns that overlap with fibromyalgia, recurrent infections, autoimmune presentations, and pregnancy planning.
I would keep Vitamin D in proportion. When a person’s symptoms, history, and risk factors suggest it may matter, it deserves to be checked and interpreted properly, usually inside an integrative medicine plan rather than as an isolated fix.
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