Vitamin D’s optimal effect on health and lifespan requires higher blood levels of the nutrient

Vitamin D plays a major role in our health. The main focus, however, is on vitamin D’s importance for bones, while many health professionals are totally unaware of the nutrient’s other essential functions. According to a review article published in Nutrients, half the global population has low vitamin D levels in the blood, which increases the risk of cardiovascular disease, hypertension, cancer, type 2 diabetes, Alzheimer’s disease, respiratory infections like COVID-19, and early death. The authors also mention that vitamin D science is often inadequate or misleading because studies focus on supplementation rather than looking at blood levels of 25(OH)D. Consequently, trials are often made with far too small vitamin D doses or with too a short a trial period. In either case, blood levels of vitamin D fail to reach their optimum. What is more, levels of 25(OH)D in the blood should ideally be above 75 nmol/L in order to protect against cardiovascular disease, cancer, and early death. Because this threshold level is higher than the official threshold levels, the scientists recommend high-dosed vitamin D levels as a way to reach an optimal nutrient status.

We get very little vitamin D from our diet. The primary source of this nutrient is UVB rays from the sun during the summer, as they enable our skin to synthesize vitamin D. Unfortunately, factors like spending too much time indoors, the winter period, ageing, overweight, dark skin, and the use of sunscreen with sun factor prevent us from producing enough vitamin D, which is why vitamin D deficiency is the most widespread of all nutrient deficiencies in the world.
The type of vitamin D that we produce in our skin is called cholecalciferol. It is an inactive precursor that the liver then converts into 25(OH)D. This is the form of vitamin D that is measured in blood tests. When cells in the body need vitamin D, the vitamin is converted into its active steroid form known as 1,25(OH)2D. This process takes place in the kidneys, the immune cells, the blood vessels, and other places. Afterwards, the active form of vitamin D is able to bind to vitamin D receptors (VDR) in pretty much every cell in the body. Here, vitamin D regulates different genes by way of on/off switches that control functions such as:

• Calcium uptake. Bones and teeth.
• Immune defense and inflammatory processes
• Lung function
• Brain and nervous system
• Insulin levels and blood sugar
• Circulatory system
• Regulation of genes that are involved in cancer development

Threshold values are only based on bone health – not the other functions

The current vitamin D recommendations and threshold levels in the blood are only based on bone health, not on all of the other functions of vitamin D. The authors of the new review article also mention that many health professionals are unaware of all the vitamin D-dependent functions that have been uncovered in the last 20 years. Many studies have been inadequate because they have only looked at the effect of vitamin D supplementation without focusing on having optimal levels of 25(OH)D in the blood. What is more, health authorities have concentrated on medical treatment of disease instead of looking into means of prevention.
To support their review article, the authors have used WHO data about death rates and the most common diseases and refer to over 94,000 publications about vitamin D that they have found at www.pubmed.cov. Also, they mention a list of different studies and meta-analyses.
According to the scientific material, vitamin D supplementation that optimizes blood levels of the nutrient is able to strengthen your health and lower the most common causes of death such as cardiovascular disease, elevated blood pressure, type 2 diabetes, respiratory infections such as COVID-19, and Alzheimer’s disease.

Cardiovascular disease

It takes many years for cardiovascular diseases to develop, and they are the leading cause of death. According to the review article, observations from 14 countries and 24 populations have found that the death rate peaks during the winter period where we are unable to produce the vitamin because the sun is not sufficiently strong. At this time of year, our blood levels of vitamin D are at their lowest.
Several studies have shown that levels of 25(OH)D in the blood are inversely related with the risk of dying of a cardiovascular disease. These studies included data about ischemic heart disease, heart failure, and stroke.
A large population study from the University of South Australia shows that those with the lowest levels of vitamin D in their blood were twice as likely to be affected by cardiovascular disease and early death, compared with people who had a sufficient level of vitamin D in their blood. Vitamin D prevents cardiovascular disease by way of several mechanisms, including the prevention of stiff arteries, atherosclerosis, and inflammation plus regulation of cholesterol, blood volume, blood pressure, and insulin levels.
The review article suggests that one should aim for blood levels above 75 nmol/L (=30 ng/ml) in order for the heart and circulatory system to have enough vitamin D. With this knowledge, millions of people could potentially avoid early death, simply by preventing a simple vitamin deficiency.

• Blood levels of vitamin are calculated as ng/ml or as nmol/L
• The lower threshold value is 50 nmol/L, which is the same as 20 ng/ml
• The upper threshold level is 160 nmol/L, which is the same as 60 ng/ml

Hypertension

The body’s vitamin D status also affects your blood pressure. A meta-analysis of several population studies with a total of 283,537 participants has shown that the risk of hypertension was 30 percent lower in the tertile of patients with the highest vitamin D levels in their blood.
An observational study has shown that participants who were given 100 micrograms of vitamin D daily to raise their blood levels above 100 nmol/L (40 ng/ml) experienced a significant blood pressure reduction. After one year, 71 percent of the participants had normal blood pressure.

• In Denmark, the official recommendations for vitamin D call for daily supplementation (5-20 micrograms) of the most vulnerable groups
• According to the review article, these levels are far too small to effectively optimize blood levels of vitamin D to help protect against various life-threatening diseases
• An observational study has shown that supplementation with 100 micrograms of vitamin D daily can raise blood levels of the nutrient to 100 nmol/L (40 ng/ml), a level that can improve blood pressure significantly

Cancer

As early as in the 1940s, scientists had observed a link between cancer mortality and exposure to UVB rays. People living at northern latitudes had an increased risk of several cancer types, and it’s still that way.
When the body’s vitamin D status is too low it can affect a number of the genes involved in protein coding and the regulation of cell division. The lack of vitamin D can also affect the body’s regulation of estrogen and inflammation. Being vitamin D-deficient will eventually increase the risk of cancer for the same reason.
A number of population studies have shown that UVB exposure from the sun is inversely correlated with around 20 different cancer types. For example, a group of Danish scientists has found that women from 50 years and older who spend a lot of time outdoors and are exposed to more sunlight – especially between 10 am and 3 pm – are less likely to develop breast cancer. The risk is reduced additionally by taking vitamin D during the winter period.
One observational study showed that women who took vitamin D supplements to raise their blood levels above 150 nmol/L (60 ng/ml) had a significantly lower risk of breast cancer. Numerous
observational studies have shown that having high levels of vitamin D in the blood (from sun exposure or supplements) can lower the risk of cancer mortality and several cancer forms. This is important because most cancers take years to develop.
Taking high-dosed vitamin D supplements for at least three years can also help cancer patients live longer, according to a study from Michigan State University in USA. It is not enough to treat cancers with surgery, chemotherapy, and radiation. You also have to optimize the body’s vitamin D status.

Type 2 diabetes and diabetic neuropathy

Type 2 diabetes is a metabolic disorder that is characterized by insulin resistance, where the cells’ ability to absorb sugar is impaired. Although type 2 diabetes is normally associated with being overweight and eating junk-food, it also appears that being vitamin D-deficient plays a role.
Science has found that the insulin-producing beta cells of the pancreas have vitamin D receptors, and it is assumed that vitamin D is needed to for the conversion of pro-insulin into insulin (pro-insulin is a precursor of insulin). Vitamin D also controls inflammation, which is seen in connection with type 2 diabetes and many of the complications related to the disease.
A Brazilian study suggests that vitamin D can improve insulin sensitivity, thereby lowering blood sugar levels and the risk of developing type 2 diabetes. Another population study (NHANES) has demonstrated that higher blood levels of 25(OH)D are linked to lower mortality from type 2 diabetes.
A Chinese study has shown that lack of vitamin D is linked to diabetic neuropathy, which is an insidious condition associated with inflammation, pain, amputations, circulatory failure, and reduced lifespan.
According to a Danish physician named Christian Stevns Hansen, low blood levels of both vitamin D and vitamin B12 is linked to an increased risk of developing diabetic neuropathy. It is therefore essential to have plenty of vitamin D in your blood to prevent type 2 diabetes and as early therapy for diabetic neuropathy. According to the review article, several studies suggest that diabetics may need 100 micrograms of vitamin D daily to optimize their blood levels of this nutrient.

• Although type 2 diabetes is normally linked to overweight and junk-food, being vitamin D-deficient may also play a role
• It seems that overweight people and diabetics have an increased need for vitamin D

COVID-19 and other respiratory infections

It is commonly known that virus infections such as the common cold, influenza, and new influenza strains typically begin in the winter period, which is where many of us lack vitamin D. During the Spanish flu (1918-1919) where 50 million people died, the mortality rate was lower in the southern regions that have more sunshine.
COVID-19 is caused by a new corona variant. By January 2022, the pandemic was reported to have killed 5.6 million people. It appears that vitamin D deficiencies were particularly common among vulnerable groups such as older people, overweight individuals, people with dark skin, and the chronically ill.
In 2020, experts believed that there were several vitamin D-dependent mechanisms that could lower the risk of being infected with COVID-19. For example, vitamin D protects against respiratory infections by promoting the release of certain antibiotic compounds such as cathelicidin and defensin that prevent viruses from replicating. Vitamin D is generally important for white blood cells and other compounds in our innate immune defense. Vitamin D is also of great importance to the adaptive immune defense. It stimulates the T cells that are especially important for fighting virus. Vitamin D is also important for the release of anti-inflammatory cytokines and for regulating the inflammatory processes. This function is extremely important because a COVID-19 infection can become complicated and potentially life-threatening if acute respiratory distress syndrome (ARDS) develops as a result of uncontrolled cytokine storm and hyperinflammation.
Since the spring of 2020, several studies have shown that lack of vitamin D increases the risk of COVID-19 infections, ARDS, intensive care admission, and death. Eighty percent of patients hospitalized with COVID-19 were vitamin D-deficient, according to a study that is published in The Journal of Clinical Endocrinology & Metabolism.
And a study from Northwestern University of Illinois, USA, showed that vitamin D-deficient patients were twice as likely to get life-threatening complications as a result of COVID-19.
In November 2020, nursing home residents and other vulnerable groups in the Spanish province, Andalusia, started getting vitamin D supplements. They got 25(OH)D because it is faster for the body to convert this form of vitamin D into the active steroid form of the nutrient. This intervention produced swift results. The number of patients in intensive care plummeted and the death rated went down by 82 per cent. Meanwhile, the death rate went up many other places in Europe, most likely because people became increasingly vitamin D-deficient during the winter period.
Treating COVID-19 patients with large doses of vitamin D is also a lifesaver, according to a Spanish pilot study. Here, hospitalized COVID-19 patients were either given standard therapy alone or high-dosed 25(OH)D supplementation combined with standard therapy.
It turned out that only two percent of the patients in the vitamin D group were admitted to intensive care, while the figure in the other group was 50 per cent. There were deaths in the vitamin D group, and everyone was discharged without further complications.
Apparently, the risk of COVID-19 infections and related complications increases in step with the vitamin D deficiency in the blood becoming more pronounced.
Vitamin D supplementation also has potential as part of the treatment of complicated infections with COVID-19 and other respiratory infections.

• Virus infections and new infection waves typically occur during the winter period where people tend to be low in vitamin D.
• You won’t notice if your body lacks vitamin D. Your immune system certainly will!

Alzheimer’s disease

Alzheimer’s disease causes neurons in different parts of the brain to perish. The disease is linked to accumulated formation of proteins called beta-amyloid and Tau. Studies suggest that local inflammation contributes to the problem, and the same goes for insulin resistance that causes lack of energy in the neurons. Alzheimer’s is also called type 3 diabetes for the same reason.
The brain neurons, glial cells, and hippocampal cells have vitamin D receptors, indicating that vitamin D is of vital importance to brain health and brain function.
According to the review article, vitamin D prevents Alzheimer’s disease from developing by counteracting the accumulation of beta-amyloid. The vitamin also counteracts inflammation and insulin resistance in the brain.
Most studies of vitamin D’s effect on Alzheimer’s disease are observational. A more recent analysis based on data from IGAP and UK Biobank have found that higher levels of vitamin D in the blood were significantly linked to a lower risk of developing Alzheimer’s disease.

Vitamin D and all-cause mortality

Numerous meta-analyses have linked blood levels of vitamin D to all-cause mortality. Danish scientists from Herlev Hospital and the University of Copenhagen made a study of 96,000 people where they found a link between low blood levels of vitamin D and early death from cancer, cardiovascular disease, and other types of disease.

• Blood levels of vitamin D should ideally be higher than 75 nmol/L (30 ng/ml) in order to prevent cardiovascular disease, and 100-150 nmol/L (40-60 ng/ml) to prevent cancer and various other diseases
• These levels are way above the official lower threshold level of 50 nmol/L (20 ng/ml)

Vitamin D from the sun and from supplements

Most people with fair skin who spend a lot of time outdoors during the summer period are able to synthesize sufficient amounts of vitamin D without getting a sunburn. During the winter period, however, the sun is not strong enough. The problem is only made worse by things like spending too much time indoors, being old, suffering from overweight, having chronic ailments, and using too much sunscreen. These factors may lead to a chronic vitamin D deficiency.
In their review article, the authors write that most people who take vitamin D in the range of 50-100 microcrams daily are able to raise their blood levels to 75-100 nmol/L (30-40 ng/ml). Both the Institute of Medicine and the European Food Safety Authority (EFSA) state that it is perfectly safe to take up to 100 micrograms of vitamin D daily. In certain cases, it is safe to take even larger quantities for shorter periods and with proper professional guidance.
Overweight people often have an increased need for vitamin D.

Study types, advantages, and disadvantages

Different types of studies are used to determine how a given factor affects disease risk and mortality. These studies have been categorized in a type of hierarchy with in-vitro studies at the bottom. Above them are animal studies, followed by population studies, and randomized placebo-controlled studies (RCT). At the top, we have meta-analyses. This hierarchy mainly applies to pharmaceutical drugs and not nutrients as vitamin D. The reason is that intake, endogenous synthesis, and utilization of vitamin D are also affected by factors like diet, genes, BMI, skin color, ageing processes, use of sunscreen, and season.
What is more, different studies of vitamin D supplementation are often too small, or the trial period is too short a period to effectively optimize blood levels of vitamin. Another important detail to include is that the body needs magnesium to convert vitamin D into the active steroid form.

References:

William B. Grant. A Narrative Review of the Evidence for Variations in Serum 25-Hydroxyvitamin D Concentration Thresholds for Optimal Health. Nutrients 2022

Debra Sullivan. What are the health benefits of vitamin D? MedicalNewsToday 2019
Anas Raed et al. Dose responses of vitamin D3 supplementation on arterial stiffness in overweight African Americans: A placebo controlled randomized trial. PLOS ONE, 2017

Pedersen JE, Strandberg-Larsen K et al. Occupational exposures to solar ultraviolet B radiation and risk of subtypes of breast cancer in Danish women. Occupational & Environmental Medicine 2021.

Varun Samji et al. Role of vitamin D supplementation for primary prevention of cancer: Meta-analysis of randomized trials. Journal of Clinical Oncology, 2019

Michigan State University. Vitamin D could help cancer patients live longer. ScienceDaily. June 2019

The North American Menopause Society (NAMS) Vitamin D could lower the risk of developing diabetes. ScienceDaily 2019

Scott LaFee. Vitamin D Deficiency Linked to Greater Risk of Diabetes. UC San Diego Health. April 2018

Plasma 25-hydroxyvitamin concentration and risk of type 2 diabetes and pre-diabetes. 12-year cohort study. PLoS One 2018

Gong Xiaohua et al. Severe Vitamin D Deficiency Is Associated With Increased Expression of Inflammatory Cytokines in Painful Diabetic Peripheral Neuropathy. Frontiers in Nutrition. 10 March 2021

Christian Stevns Hansen. Almindelige vitaminer og mineraler er forbundne med alvorlige komplikationer hos diabetes patienter. Formidling af Ph.d. afhandlingen: Exploring new risk markers for diabetic cardiovascular autonomic neuropathy.

Laurence Dollimore. Watch: British MP praises Andalucía for using vitamin D to treat COVID-19 patients and ask PM Boris Johnson to follow Spain´s example. The Olive Press February 16, 2021

David Davis. Vitamin D: Covid-19. In the House of Commons 14th January 2021

Marta Entrenas Castillo et al. Effect of calciferol 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. October 2020

Iacopo Chiodini et al., Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical outcomes. Frontiers in Public Health. 22 December 2021

Asma Kazemi et al. Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis. Advanced Nutrients 2021 Oct
Afzal Shoaib et al. Genetically low vitamin D concentration and increased mortality: Mendelian randomization analysis in three large cohorts. British Medical Journal. 2014

Københavns Universitet. Det Sundhedsvidenskabelige Fakultet. Lave niveauer af d-vitamin øger dødeligheden. 2014

Qi Dai et al. Magnesium status and supplements influence vitamin D status and metabolism: results from a randomized trial. The American Journal of Clinical Nutrition. 2018