(Mercola)—Vitamin D has long been known for its crucial role in bone health, but it has body-wide effects and may be just as important for your mental well-being. A comprehensive systematic review examined the effects of vitamin D supplementation on various mental and neurological disorders, including depression, bipolar disorder, schizophrenia, epilepsy and neuroinflammation.¹

The findings indicate that vitamin D could play a significant role in managing these conditions. Interestingly, vitamin D receptors are present in various crucial brain regions, where it influences neuron development, growth factor production and neurotransmitter synthesis.²

This connection between vitamin D and brain function may explain its potential impact on mental health. The review, published in the journal Diseases, found that vitamin D deficiency is prevalent among individuals with mental health disorders, revealing a link between low vitamin D levels and the development or exacerbation of these conditions.³

Sun exposure is the best way to raise your vitamin D level. That said, if you’ve been eating a diet high in vegetable oils or seed oils, you need to be cautious, as these oils increase your risk of sunburn. That’s why I recommend avoiding high-intensity sun exposure unless you’ve been off these oils for at least four to six months.

Vitamin D Offers a Ray of Hope for Depression

When it comes to depression, the research on vitamin D’s effectiveness shows promising results. Several studies have found that lower levels of vitamin D are associated with more severe depressive symptoms. In fact, a meta-analysis published in The British Journal of Psychiatry revealed that low vitamin D levels were linked to a significantly higher risk of depression.⁴

Some randomized controlled trials have shown that vitamin D supplementation can lead to significant improvements in depression scores, particularly in overweight and obese individuals.⁵ The effect of vitamin D on depression could be attributed to its role as a unique neurosteroid hormone.

As a neurosteroid, vitamin D supports neurotrophic factors, provides neuroprotection and contributes to brain development. It’s also thought to influence the serotonergic system and help maintain healthy circadian rhythms, both of which are associated with mood regulation.

Epilepsy: Seizing Control with Vitamin D

Your vitamin D levels may also play a crucial role if you’re dealing with epilepsy. Research has shown that individuals with epilepsy frequently have inadequate levels of vitamin D, defined as a 25-hydroxyvitamin D3 concentration less than 20 ng/mL. Preclinical research and preliminary human data suggest that vitamin D3 may help regulate or suppress seizures through both membrane-based and genomic mechanisms.⁶

One study found that in a group of people with epilepsy, there was an average 40% reduction in seizures after subjects were given vitamin D supplementation.⁷ Notably, 38% of the participants experienced a 50% or greater reduction in their seizure frequency.

Another study demonstrated that low serum vitamin D levels were prevalent in 86.8% of the 542 people with epilepsy that were examined, underscoring the importance of regular vitamin D screening for individuals with epilepsy.⁸ This intervention could help reduce the risk of future complications and potentially improve seizure control.

Vitamin D for Bipolar Disorder and Alzheimer’s Disease

While the evidence for vitamin D’s benefits in depression and epilepsy is compelling, the results for other mental health conditions are mixed. In bipolar disorder, some studies have found elevated levels of vitamin D binding protein in patients, suggesting a potential link to inflammation.⁹ However, the impact of vitamin D supplementation on bipolar symptoms remains unclear.

For schizophrenia, the relationship with vitamin D is even more complex. Although vitamin D deficiency is common in individuals with schizophrenia, studies have not consistently shown benefits from supplementation.

When it comes to neuroinflammation, animal studies have demonstrated promising results, with vitamin D therapy shown to reduce inflammation in rat models of traumatic brain injury.¹⁰ Additionally, vitamin D deficiency has been associated with an increased risk of neurodegenerative diseases like Alzheimer’s and vascular dementia.¹¹

Vitamin D and Mental Health: New Insights

Recent research presented at the American Society for Nutrition’s annual NUTRITION meeting also shed light on the relationship between vitamin D levels and mental health, particularly depressive symptoms. Dr. Jacqueline A. Vernarelli, associate professor at Sacred Heart University in Connecticut, and her research partner, Kayla D. Champagne, analyzed data from 4,641 adults who participated in the 2017-2018 National Health and Nutrition Examination (NHANES) survey.¹²

Their findings revealed a significant connection between vitamin D levels and mental health outcomes. Adults with lower levels of vitamin D in their blood exhibited more depressive symptoms, while those with depression had significantly lower intake of vitamin D compared to adults without depression.

This large-scale study provides compelling evidence for the importance of maintaining adequate vitamin D levels for your mental wellbeing.

The researchers suggest that public health messaging encouraging the consumption of vitamin D-rich foods could be an essential dietary strategy to support mental health, although sensible sun exposure is the ideal way to boost your vitamin D levels — and supplementation may be necessary for some people, especially during winter months or for those with limited sun exposure.

In addition to its impact on mental health, the study also uncovered a link between vitamin D levels and physical functioning. Higher serum vitamin D levels were associated with improved physical performance.¹³ This means addressing vitamin D deficiency offers not only benefits for mood improvement but also for enhanced physical capabilities and overall quality of life.

Vitamin D May Reduce Lifetime Depression Risk in Those Who Are Deficient

Recent research has employed a powerful technique called Mendelian randomization to investigate the causal relationship between vitamin D levels and mental health outcomes.¹⁴ This method uses genetic variants associated with vitamin D levels as proxies to assess the impact of vitamin D on various conditions. A large-scale study using data from 333,025 participants in the UK Biobank found intriguing results.

While there was no strong evidence for a linear relationship between vitamin D levels and conditions like fibromyalgia, clinical fatigue or chronic widespread pain across the entire population, the study revealed a potential threshold effect for depression.¹⁵

Specifically, individuals with the lowest levels of genetically-predicted vitamin D showed a reduced risk of probable lifetime major depression when their vitamin D levels increased. The genetic approach helps overcome limitations of observational studies, providing more reliable evidence for a causal link between vitamin D and depression in those with low levels.

Vitamin D’s Complex Role in Brain Health

The relationship between vitamin D and mental health is multifaceted. Vitamin D receptors are present in various brain regions, indicating its importance in neurological function. Additionally, vitamin D has been observed to have anti-inflammatory effects in the brain, potentially preventing oxidative damage to nervous tissue.

Some studies have even suggested a connection between vitamin D and the gut microbiome,¹⁶ which is increasingly recognized for its role in mental health. These diverse mechanisms highlight why addressing vitamin D deficiency could be particularly important for your brain health, especially if your levels are low.

However, the complexity of these interactions also explains why the effects of vitamin D supplementation may not be uniform across all individuals or all mental health conditions.

Vitamin D Deficiency: A Hidden Risk Factor for Depression

A large-scale study analyzing data from 15,156 U.S. adults also found that vitamin D deficiency is significantly associated with an increased risk of depression.¹⁷ Specifically, individuals with adequate vitamin D levels were about 24% less likely to experience depression compared to those who were deficient. This finding held true even after accounting for various factors like gender, race, education and marital status.

The implications are clear: maintaining healthy vitamin D levels could be an effective strategy for safeguarding your mental health. Vitamin D influences mood through several mechanisms, including regulating calcium levels in brain cells.

Contrary to popular belief, the study revealed that younger adults may actually be at higher risk for vitamin D deficiency than older individuals. For every 20-year decrease in age, the likelihood of vitamin D deficiency increased by 37.1%.¹⁸ This unexpected finding challenges previous assumptions and highlights the importance of vitamin D awareness across all age groups.

Younger people’s higher metabolic rates and potentially greater physical activity levels might contribute to their increased vitamin D needs. However, when it comes to depression, the study confirmed that risk does increase with age. For each 20-year increase in age, the prevalence of depression rose by 9.2%.¹⁹

This age-related increase in depression risk may be attributed to various factors, including physiological changes in the brain, accumulated life experiences and increased social isolation among older adults. These findings underscore the complex interplay between age, vitamin D status and mental health.

Vitamin D’s Impact on Specific Mental Health Conditions

While depression has been the primary focus of vitamin D research in mental health, studies have revealed its potential influence on other conditions as well.²⁰ For instance, vitamin D deficiency has been linked to an increased risk of schizophrenia, with some research suggesting that prenatal vitamin D deficiency may be a risk factor. In bipolar disorder, lower vitamin D levels have been observed.

Anxiety disorders have also shown a potential connection to vitamin D status, with some studies indicating that supplementation may improve anxiety symptoms.²¹ Interestingly, vitamin D deficiency has been associated with obsessive-compulsive disorder and post-traumatic stress disorder (PTSD) as well.

In neurocognitive diseases like Alzheimer’s, low vitamin D levels correlate with a higher degree of cognitive impairment,²² underscoring the wide-reaching impact of vitamin D on various aspects of mental health.

By taking proactive steps to maintain optimal vitamin D levels and adopting a healthy lifestyle, you can help reduce your risk of depression and other mental health conditions and support your mental health throughout your lifespan.

Natural Sunlight: The Optimal Source of Vitamin D

Obtaining vitamin D through proper sun exposure is highly recommended, as it offers benefits beyond just vitamin D production. In fact, higher vitamin D levels may indicate healthy sun exposure, which could be responsible for many health benefits attributed to vitamin D, including reduced cancer risk and increased longevity.

Regular sunlight exposure also boosts melatonin production, a powerful anticancer agent.²³ That said, while sun exposure is essential for vitamin D production and health, it can also be harmful if you’re not careful. The key is understanding how to protect yourself while still reaping the benefits. So, let’s talk about some strategies that can help you do that.

If you’ve been eating a diet high in vegetable oils or seed oils, you need to be extra cautious with sun exposure. These oils are rich in linoleic acid (LA), an omega-6 fat that is highly prone to oxidation when exposed to ultraviolet (UV) radiation. When sunlight interacts with skin containing these oils, it causes the oils to break down, leading to inflammation and DNA damage.

That’s why I recommend avoiding sun exposure unless you’ve been off these oils for at least four to six months. Your individual physical characteristics also influence your relationship with the sun. Skin color, determined by melanin content, is a prime example.

Melanin acts as a natural sunscreen, meaning darker-skinned individuals require more sun exposure to produce the same amount of vitamin D as those with lighter skin. This biological variation emphasizes the need for personalized approaches to sun exposure.

Body composition, particularly fat percentage, is another crucial factor. Adipose tissue can store fat-soluble compounds, including oxidized vegetable oils. Individuals with higher body fat may therefore need to be more cautious, as these stored oils can prolong the risk period even after dietary changes.

The best way to assess your sun exposure, especially if you have a history of consuming vegetable oils, is to monitor your skin for any signs of redness or burning. This simple “sunburn test” considers the time of year, skin type and more. If you don’t notice even the slightest hint of pink on your skin, it’s a good sign that your sun exposure was within a safe range. Always aim to avoid sunburn, as it indicates overexposure.

As you lower your body’s stores of LA, your risk of sunburn and skin cancer decreases dramatically. However, it’s still important to be mindful of your sun exposure, especially during the transition period. As you begin reducing vegetable oils in your diet, avoid peak sunlight hours, which are typically an hour before and after solar noon.

In most of the U.S. during summer, this means staying out of direct sun from 11 a.m. to 3 p.m. during Daylight Saving Time, or 10 a.m. to 2 p.m. in Standard Time. Over time, as your body detoxes the accumulated seed oils, you can gradually increase your time in the sun. Eventually, you will be able to enjoy an hour or more of peak sunlight hours.

Remember, everyone’s skin is different, so listen to your body during this adjustment period. The key is to never let your skin burn. Sunburn is a sign of damage, so if you notice any redness, seek shade at once. By being mindful of your sun exposure, you’re taking an important step in caring for your health.

Tips for Safer Sun Exposure

If you do need to spend time in the sun before your body has fully cleared out seed oils, there are some protective strategies you can implement. One of my favorite recommendations is astaxanthin, a powerful antioxidant found in certain marine life. Taking 12 milligrams of astaxanthin once a day can help increase your skin’s resistance to sun damage. It works by neutralizing free radicals and reducing inflammation. This gives your skin extra protection against UV radiation.

Another helpful tool in your sun-protection arsenal is niacinamide cream. Niacinamide, also known as vitamin B3, has been shown to help protect against UV-induced DNA damage when applied topically. It can also improve your skin’s barrier, making it more resilient to stressors like sun exposure. I’ve seen patients have remarkable success with applying niacinamide cream before sun exposure.

Here’s a tip that might surprise you. Taking a baby aspirin 30 to 60 minutes before sun exposure could lower your risk of skin cancer. Aspirin prevents the LA in your skin from turning into harmful compounds called OXLAMs (oxidized linoleic acid metabolites). These OXLAMs are a primary contributor not just to skin cancer but to many types of cancer. By inhibiting their formation, aspirin can provide an extra layer of protection against sun damage.

Molecular hydrogen (H₂) offers another layer of protection against sun damage and mitigates the harmful effects of vegetable oils. This remarkable molecule works at the cellular level, effectively reducing oxidative stress by neutralizing harmful free radicals, with a particular affinity for the highly reactive hydroxyl radical. H₂‘s unique properties allow it to penetrate cell membranes easily, directly targeting sources of inflammation and oxidative damage.

Importantly, it does this without interfering with beneficial reactive oxygen species (ROS), maintaining the body’s delicate oxidative balance. Beyond this protective role, molecular hydrogen also provides other benefits, including increased energy levels, and enhanced recovery. This makes H₂ a valuable tool in your arsenal for supporting cellular health, especially when facing environmental stressors like sun exposure or dietary challenges from vegetable oil consumption.

If you can’t get enough sun daily, vitamin D supplements may be necessary. Vitamin D deficiency and insufficiency are prevalent globally, affecting 40% to 100% of the population.²⁴

The current definition of deficiency (less than 20 ng/mL) has been shown to be inadequate for good health and disease prevention, suggesting an even higher prevalence of suboptimal vitamin D levels. To determine your ideal sun exposure or supplement dosage, it’s crucial to measure your vitamin D levels twice a year.

After testing, adjust your sun exposure or vitamin D3 supplementation accordingly. Retest in three to four months to ensure you’ve reached your target level. The optimal range for health and disease prevention is 60 to 80 ng/mL (150 to 200 nmol/L), with sufficiency starting around 40 ng/mL (100 nmol/L in Europe). Regular testing and adjustments will help you maintain ideal vitamin D levels for your health.

• ^{1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11} Diseases. 2024 Jun; 12(6): 131
• ^12, 13 Healio July 9, 2024
• ^14, 15, 16 Transl Psychiatry. 2024; 14: 274
• ^17, 18, 19 BMC Psychiatry. 2023; 23: 534
• ^20, 21, 22 Medicina (Kaunas). 2023 Dec; 59(12): 2056
• ²³ YouTube, The Joe Cohen Show, Episode 1, October 25, 2022, 4:00
• ²⁴ Endocr Pract. 2021 May; 27(5): 484–493, Introduction

(Mercola)—I strongly recommend getting sensible sun exposure each day, and one of the reasons why is because it helps naturally optimize your vitamin D levels. Low vitamin D levels are linked to an increased risk of cancers,¹ while vitamin D can attach to the vitamin D receptor (VDR) in your cells, setting off a series of signals that may affect how they grow, develop and survive.²

In this way, vitamin D acts like a brake on the process of cell growth in many tissues of the body, helping to control the speed at which cells multiply. This is particularly important when it comes to cancer because one of the key features of this disease is cells growing out of control. Moreover, vitamin D has been observed in animal studies to help delay some age-related changes by activating another important pathway via the vitamin D receptor.

This pathway involves a molecule called Nrf2, which plays a crucial role in protecting your body from oxidative stress and DNA damage — two factors that are commonly linked to the development of cancer.³ Overall, evidence continues to accumulate showing that vitamin D is a strong ally to combat cancer.⁴

Vitamin D Reduces Cancer Mortality

Worldwide, cancer is the No. 2 cause of death, behind only cardiovascular disease.⁵ Meanwhile, the global prevalence of vitamin D deficiency (defined as a level of less than 20 ng/mL) and insufficiency (defined as a level of 20 to less than 30 ng/mL) is 40% to 100%.⁶ Although increasing vitamin D levels may help to reduce cancer deaths, health officials rarely recommend optimizing levels for this purpose.

For example, research has shown that once you reach a minimum serum vitamin D level of 40 ng/mL, your risk for cancer diminishes by 67%, compared to having a level of 20 ng/mL or less.⁷

A 2023 systematic review and meta-analysis published in Ageing Research Reviews also found vitamin D3 supplementation reduced cancer mortality by 6%. This wasn’t considered statistically significant, but when only studies involving daily vitamin D intake were analyzed, cancer mortality dropped by a significant 12%.⁸ According to the researchers:⁹

“From a biological perspective, it is plausible that a sufficient vitamin D status has an impact on cancer prognosis: by binding to the vitamin D receptor (VDR), the active hormone 1,25-dihydroxyvitamin D (1,25(OH)2D) influences signaling pathways that regulate cell proliferation, differentiation, and cell survival, and thus acts as an anti-proliferative agent in many tissues and can slow the growth of malignant cells.”

Other research also supports vitamin D’s role in protecting against cancer death. In one study of 25,871 patients, vitamin D supplementation was found to reduce the risk for metastatic cancer and death by 17%. The risk was reduced by as much as 38% among those who also maintained a healthy weight.^10,11

What’s particularly noteworthy is this study only gave participants 2,000 IU of vitamin D daily and didn’t measure their blood levels. Despite these research flaws, a significant benefit was still found. However, other research has found even more striking benefits, including a GrassrootsHealth analysis published in PLOS ONE.

It showed women with a vitamin D level at or above 60 ng/mL (150 nmol/L) had an 82% lower risk of breast cancer compared to those with levels below 20 ng/mL (50 nmol/L).¹² Meanwhile, risks of lung cancer, colorectal cancer, breast cancer, bladder cancer and lymphoma are higher in people with low vitamin D levels, while having higher levels is associated with a better prognosis in cases of breast and colorectal cancers.¹³

The Ageing Research Reviews study further revealed that daily vitamin D supplementation was particularly beneficial for people aged 70 and over, as well as those who took vitamin D daily and were later diagnosed with cancer. Study author Ben Schöttker, Ph.D., with the German Cancer Research Center in Heidelberg, further explained:¹⁴

“This does imply that basically everyone aged 50 and older, including people who have never had cancer, might profit from vitamin D supplementation if they are vitamin D insufficient … Doctors cannot know who might develop cancer at a later time.”

Vitamin D Has Anticancer Effects Against Many Types of Cancer

A mini review on the impact of vitamin D on cancer, published in The Journal of Steroid Biochemistry and Molecular Biology, pointed out that while vitamin D is widely recognized for its essential role in regulating the balance of minerals in the body, a deficiency has been linked to the onset and progression of various cancers.¹⁵ Vitamin D targets cancer in multiple ways, including:¹⁶

• Anticancer effects, which means it targets different stages of cancer development and progression, including the initiation, growth and spread of cancer cells.
• Antimetastatic effects, which refers to the ability to stop cancer cells from spreading from the original tumor site to other parts of the body. Since metastasis is often responsible for the fatal outcomes of cancers, preventing the spread can significantly improve survival rates.
• Anti-tumorigenic, meaning vitamin D helps prevent tumor formation or the growth of tumors. This can involve mechanisms like inducing cell death in cancer cells, blocking cell cycle progression, or inhibiting pathways that fuel tumor growth.

The review highlighted vitamin D’s role against the following cancers:¹⁷

• Breast
• Prostate
• Bladder
• Colon
• Glioblastoma
• Melanoma
• Squamous cell carcinoma
• Ovarian
• Multiple myeloma
• Osteosarcoma
• Head and neck

In terms of breast cancer, the leading cause of death for women globally, vitamin D deficiency is common among patients, and those who are deficient are more likely to have more aggressive and harder-to-treat subtypes of breast cancer, such as higher grade and estrogen receptor-negative tumors.

The study also highlighted the role of genetic differences in the VDR that could influence breast cancer risk. In particular, in certain populations like North Indian women from New Delhi, variations in the VDR gene were identified as potential risk factors.¹⁸

In prostate cancer — the most common cancer in men — low levels of vitamin D were linked to high levels of dihydrotestosterone (DHT) in the prostate which is associated with the progression of prostate cancer.¹⁹ In addition, vitamin D may influence the activity of sirtuin 1 (SIRT1), which is known as a longevity protein. Optimizing your vitamin D levels may help boost your body’s natural cancer defenses, in part, via mechanisms involving SIRT1.²⁰

Additional research suggests there may be considerable variation in how different individuals’ genes respond to vitamin D supplementation, which might explain why not everyone benefits equally from extra vitamin D.

For best results, the scientists suggest vitamin D supplementation should be personalized and “advocate for options tailored to individual vitamin D needs, combined with a comprehensive intervention that favors prevention through a healthy environment and responsible health behaviors.”²¹

Why Sun Exposure Is the Best Source of Vitamin D

On a typical sunny day, your body may produce up to 25,000 international units (IU) of vitamin D,²² although many people aren’t in the sun enough to optimize their vitamin D levels. However, I strongly recommend getting your vitamin D from proper sun exposure, if possible, as it provides benefits beyond vitamin D optimization.

Higher levels of vitamin D may even serve as a marker for healthy sun exposure, which in turn may be responsible for many of the health benefits, which include reduced risk of cancer and increased longevity, attributed to vitamin D. Regular sun exposure, for instance, enhances production of melatonin — a potent anticancer agent.²³

Near-infrared rays from the sun penetrate deep into your body and activate cytochrome c oxidase, which in turn stimulates the production of melatonin inside your mitochondria. Your mitochondria produce ATP, the energy currency of your body. A byproduct of this ATP production is reactive oxidative species (ROS), which are responsible for oxidative stress.

Excessive amounts of ROS will damage the mitochondria, contributing to suboptimal health, inflammation and chronic health conditions such as diabetes, obesity and thrombosis (blood clots). But melatonin essentially mops up ROS that damage your mitochondria. So, by getting plenty of sun exposure during the day, your mitochondria will be bathed in melatonin, thereby reducing oxidative stress.^24,25

If you’re unable to get adequate sun exposure each day, vitamin D supplementation may be necessary. Keep in mind that 20 ng/mL, which is often used as the cutoff for vitamin D deficiency, has repeatedly been shown to be grossly insufficient for good health and disease prevention, which means the true prevalence of people without optimal levels of vitamin D is even greater.

The only way to determine how much sun exposure is enough and/or how much vitamin D3 you need to take is to measure your vitamin D level, ideally twice a year. Once you’ve confirmed your vitamin D levels via testing, adjust your sun exposure and/or vitamin D3 supplementation accordingly. Then, remember to retest in three to four months to make sure you’ve reached your target level.

The Optimal Vitamin D Level for Cancer Prevention

The optimal level for health and disease prevention, including cancer prevention, is between 60 ng/mL and 80 ng/mL (150-200 nmol/L), while the cutoff for sufficiency appears to be around 40 ng/mL. In Europe, the measurements you’re looking for are 150 to 200 nmol/L and 100 nmol/L respectively.

It’s important to remember that calcium, vitamin D3, magnesium and vitamin K2 must be properly balanced for optimal overall health. Your best and safest bet is to simply eat more calcium-, magnesium- and vitamin K2-rich foods, along with sensible sun exposure.

However, if you find supplementation is necessary after a serum vitamin D test, also supplement with magnesium and vitamin K2 (MK-7) to ensure proper balance. You’ll also want to ensure you’re following an overall healthy lifestyle to reduce your cancer risk as much as possible. As researchers explained in Nutrients:²⁶

“Vitamin D supplementation is not the magic pill that miraculously solves the cancer burden or that can replace a healthy lifestyle. It is necessary to foster a good environment and invigorate a healthy lifestyle, including a high-quality diet and physical activity. Both have been proven to confer health benefits in many diseases, including cancer, and are the best preventive measures available.”

• ^{1, 15, 16, 17, 18, 19} The Journal of Steroid Biochemistry and Molecular Biology July 2023, Volume 231, 106308
• ^2, 3 Ageing Research Reviews June 2023, Volume 87, 101923, Introduction
• ⁴ Substack, Dr. William Makis, April 18, 2024
• ⁵ J Thorac Dis. 2017 Mar; 9(3): 448–451
• ⁶ Endocr Pract. 2021 May; 27(5): 484–493., Introduction
• ⁷ PLOS ONE 2016; 11 (4): e0152441
• ^8, 9, 13 Ageing Research Reviews June 2023, Volume 87, 101923
• ¹⁰ JAMA Network Open 2020;3(11):e2025850
• ¹¹ The Sentinel November 22, 2020
• ¹² PLOS ONE June 15, 2015 (PDF)
• ¹⁴ Medical News Today May 17, 2023
• ²⁰ Int. J. Mol. Sci. 2023, 24(7), 6154; doi: 10.3390/ijms24076154
• ^21, 26 Nutrients 2022, 14(21), 4512; doi: 10.3390/nu14214512
• ²² J Steroid Biochem Mol Biol. 2019 May;189:228-239. doi: 10.1016/j.jsbmb.2018.12.010. Epub 2019 Jan 4., Abstract
• ²³ Youtube, The Joe Cohen Show, Episode 1, October 25, 2022, 4:00
• ²⁴ Physiology February 5, 2020 DOI: 10.1152/physiol.00034.2019
• ²⁵ YouTube, MedCram, Sunlight: Optimize Health and Immunity January 21, 2022

• Since December 2021, four large systematic meta-analyses have been published, looking at either vitamin D levels, supplementation or both. In all cases, the data consistently show that low vitamin D levels raise your risk of COVID while higher baseline levels and/or supplementation lowers all risks by 1.5 to three times
• In the first of these four meta-analyses, the odds of developing COVID-19 among those with deficient or insufficient vitamin D levels were 1.46 times higher than those with sufficient vitamin D. Their risk of severe disease was also 1.9 times higher, and their risk of death 2.07 times higher
• In the second study, the odds of ICU admission based on vitamin D status were 2.63 times higher among those with severe vitamin D deficiency, 2.16 times higher among those with deficiency, and 2.83 times higher among those with insufficient levels. Mortality was also much higher in all patients with low levels
• In the third analysis, only 12.19% of COVID patients who received vitamin D required ICU admission, compared to 26.27% of those who did not get vitamin D
• The fourth and most recent analysis found “significant associations of vitamin D supplementation with COVID-19, encompassing risks of disease worsening and mortality,” especially in seasons characterized by vitamin D deficiency and in patients with mild to moderate infection

At this point, there is simply no question that vitamin D optimization is a crucial component of COVID-19 prevention and treatment. In addition to the many studies published during 2020 and 2021, since December 2021, four large systematic meta-analyses^1,2 have been published, looking at either vitamin D levels, supplementation or both.

In all cases, the data consistently show that low vitamin D levels raises your risk of COVID while higher baseline levels and/or supplementation lowers all risks by 1.5 to three times.

Therapeutic Role of Vitamin D in COVID

In the first of these four meta-analyses, “Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-Analysis,”³ published December 11, 2021, the researchers sought to determine “the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality and role of vitamin D in its treatment.”

A total of 72 observational studies, covering 1,976,099 patients, met the criteria for inclusion. Compared to those with sufficient vitamin D, the odds of developing COVID-19 among those with deficient or insufficient vitamin D levels were 1.46 times higher.

Their risk of severe disease was also 1.9 times higher, and their risk of death 2.07 times higher. One potential drawback was that all studies ranked “high” for risk of bias. The studies also differed in their definitions of severe illness and vitamin D deficiency/insufficiency, making absolute comparisons difficult. That said, the authors concluded:⁴

“Multiple observational studies involving nearly two million adults suggest vitamin D deficiency/insufficiency increases susceptibility to COVID-19 and severe COVID-19, although with a high risk of bias and heterogeneity. Association with mortality was less robust.”

Vitamin D Status and Clinical Outcomes

In the second study, “Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes,”⁵ published December 22, 2021, the researchers assessed “whether vitamin D status is associated with the COVID-19 severity, defined as ARDS requiring admission to intensive care unit (ICU) or mortality (primary endpoints) and with the susceptibility to SARS-CoV-2 and COVID-19-related hospitalization (secondary endpoints).”

Here, they included 54 observational studies (1,403,715 patients) that measured the association between vitamin D status and risk of COVID infection, hospitalization, ICU admission and death during hospitalization. The measures for vitamin D status were as follows:

• Insufficiency — less than 75 nmol/L (30 ng/mL)
• Deficiency — less than 50 nmol/L (20 ng/mL)
• Severe deficiency — less than 25 nmol/L (10 ng/mL)

Seventeen studies reported the association between vitamin D status and SARS-CoV-2 infection; nine reported the association with COVID-19 related hospitalization, 27 reported COVID-19-related ICU admission, and 35 reported COVID-19 related mortality. In summary, the odds of ICU admission based on vitamin D status were as follows:

• Severe deficiency — 2.63 times higher
• Deficiency — 2.16 times higher
• Insufficiency — 2.83 times higher

Those with severe deficiency were also 1.68 times more likely to test positive; those with deficiency were 1.83 times more likely to test positive; and those with insufficiency were 1.49 times more likely to test positive. In conclusion, the authors stated:⁶

“Patients with low vitamin D levels present an increased risk of ARDS requiring admission to intensive care unit (ICU) or mortality due to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2 infection and related hospitalization.”

The Effect of Vitamin D Supplementation

The third study, “The Effect of Vitamin D Supplementation on Mortality and Intensive Care Unit Admission of COVID-19 Patients. A Systematic Review, Meta-Analysis and Meta-Regression,”⁷ was published in May 2022.

Six studies, involving 860 patients, had data on ICU admission. Of those 860 patients, 369 received vitamin D supplementation and 491 did not, and the effect of vitamin D supplementation was found to be quite significant — 12.19% of patients who received vitamin D required ICU admission, compared to 26.27% of those who did not get vitamin D.

The data in all six studies strongly favored vitamin D. The ideal dose, however, remains uncertain, as no linear relationship between dose and odds ratio of ICU admission was observed.

Vitamin D and SARS-CoV-2 Infection, Severity and Mortality

The fourth and most recent study, “Vitamin D and SARS-CoV-2 Infection, Severity and Mortality: A Systematic Review and Meta-Analysis,”⁸ was published July 6, 2022, in PLOS ONE.

Here, they looked at COVID-19 in relation both to baseline vitamin D status and supplementation. Thirty-eight studies — including two randomized controlled trials — were included that had risk estimates for at least one endpoint (risk of infection, severity and/or mortality). In all, data on vitamin D status was available for 205,565 patients and 2,022 who were given vitamin D supplementation. According to the authors:⁹

“Random effects models showed that supplementation was associated with a significant lower risk of both COVID-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies).

There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes.

Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies.

We found significant associations of vitamin D supplementation with COVID-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients.”

Why Randomized Controlled Trials Are Not Required

As noted by in a Twitter thread by Karl Pfleger, Ph.D., the data clearly show vitamin D is strongly correlated with all COVID-19 risks, and we do not actually need randomized controlled trials to draw this conclusion:¹⁰

“Most underlying studies are observational, but at the very least knowledge of whether someone supplements D or of their D status is strongly predictive of their COVID risks/outcomes. As I’ve noted previously, RCTs are not required for this conclusion to be sound & unquestionable. This establishes a risk factor & most other well known COVID risks factors are also based entirely on observational data.

The data showing age, above-normal-weight, & comorbidities are significant risk factors is also based entirely on correlation. No RCTs establish these as risk factors but no one questions that they are. VDD [vitamin D deficiency] should be thought of as another comorbidity, just like diabetes.”

Indeed, at this point, the importance of vitamin D in the fight against COVID ought to be common knowledge everywhere, especially in health care circles. Yet the surgeon general of Florida, Joseph Ladapo, is the only public health official who is actually recommending vitamin D optimization for COVID.¹¹

This is crazy, as the effects of vitamin D were evident very early on in the pandemic. I launched an information campaign about vitamin D back in June 2020, which included the release of a downloadable scientific report that detailed the science behind vitamin D. This report, as well as a two-minute COVID risk quiz is available on StopCovidCold.com.

In December 2020, more than 100 doctors, scientists, Ph.D.’s and leading authorities from 33 countries also signed an open letter¹² to the governments and health officials of the world, calling for the use of vitamin D against COVID. Since then, the list of signatories has grown to 220.

The letter recommended taking enough vitamin D to achieve a blood level of at least 30 ng/mL (75 nmol/L), urged testing of all hospitalized COVID-19 patients and adding vitamin D to the treatment protocol for any patient whose level was below 30 ng/mL.

Not only did health agencies roundly ignore this sound advice, but they also publicly tried to discredit the notion that vitamin D could have any benefit at all, and attacked anyone sharing the good news about vitamin D.

As just one example, in the summer of 2020, the Center for Science in the Public Interest (CSPI), a self-proclaimed consumer advocacy group bankrolled by the Rockefeller Foundation, among others, launched a campaign against Mercola.com. The CSPI falsely accused me of “profiteering from the pandemic” by selling nutritional supplements, including vitamin D, while sharing scientific truth about its benefits.

The campaign culminated in a warning letter from the U.S. Food and Drug Administration, in which they warned me to stop talking about vitamin D. I reviewed this censorship attempt in “Why Is Info on COVID and Vitamin D Deficiency Suppressed?”

The fact of the matter is, data show vitamin D supplementation lowers your risk of a positive test, speeds viral clearance, slows the spread of infection, and lowers your risk of severe infection, hospitalization and death, as summarized in “Vitamin D Deficiency and COVID-19 Severity” and many other articles.

Mechanisms Behind Vitamin D

At the end of October 2020, I published my own vitamin D review¹³ in the peer-reviewed journal Nutrients, co-written with William Grant, Ph.D., and Dr. Carol Wagner, both of whom are part of the GrassrootsHealth expert vitamin D panel. You can read the paper for free on the journal’s website.

As noted in that paper, dark skin color, increased age, preexisting chronic conditions and vitamin D deficiency are all features of severe COVID disease and, of these, vitamin D deficiency is the only factor that is readily and easily modifiable.

You may be able to reverse chronic disease, but that typically takes time. Optimizing your vitamin D, on the other hand, can be achieved in just a few weeks, thereby significantly lowering your risk of severe COVID-19.

In our paper, we review several of the mechanisms by which vitamin D can reduce your risk of COVID-19 and other respiratory infections, including but not limited to the following:¹⁴

• Reducing the survival and replication of viruses¹⁵ and inflammatory cytokine production
• Maintaining endothelial integrity — Endothelial dysfunction contributes to vascular inflammation and impaired blood clotting, two hallmarks of severe COVID-19
• Increasing angiotensin-converting enzyme 2 (ACE2) concentrations, which prevents the virus from entering cells via the ACE2 receptor — ACE2 is downregulated by SARS-CoV-2 infection, and by increasing ACE2, you also avoid excessive accumulation of angiotensin II, a peptide hormone known to increase the severity of COVID-19

Vitamin D is also an important component of COVID-19 prevention and treatment for the fact that it:

• Boosts your overall immune function by modulating your innate and adaptive immune responses and reduces respiratory distress¹⁶ and improves overall lung function
• Regulates inflammatory cytokine production, which is one of the lethal hallmarks of COVID-19
• Helps produce surfactants in your lungs that aid in fluid clearance¹⁷ and lowers your risk of comorbidities, including obesity,¹⁸ Type 2 diabetes,¹⁹ high blood pressure²⁰ and heart disease²¹

Data from 14 observational studies — summarized in Table 1 of our paper²² — suggest that vitamin D blood levels are inversely correlated with the incidence and/or severity of COVID-19 and, importantly, that the evidence currently available generally satisfies Hill’s criteria for causality in a biological system.²³

Why Sun Exposure Is the Best Way to Optimize Vitamin D

The ideal way to optimize your vitamin D level is by exposing large portions of bare skin to the sun. I take an hour-long walk during solar noon every day, wearing just shorts and a baseball cap, and have not needed oral vitamin D supplementation for over 13 years.

This is not some theoretical obsession I have. I am now beyond convinced that swallowing vitamin D is exponentially inferior to getting it from the sun. I would encourage you to do everything in your power to get it from the sun. And, when you get it from the sun, you should not be swallowing it.

It is important to regularly check your vitamin D levels to see how you are doing with your program. Ideally, your level should be between 60 ng/mL and 80 ng/mL. Mine has been mid-90s this summer with no oral supplementation. Remember, vitamin D is a biomarker for all the good things the sun does for you.

Sun exposure also provides other biological health benefits over and beyond vitamin D production. If the science of sun exposure interests you, check out Dr. Roger Seheult’s MedCram lecture above.

In it, he explains the ins and outs of how sunlight impacts your health. One really important health benefit you can only get from sunlight and not oral supplementation is mitochondrial melatonin production.

The best review of the sun’s effect on melatonin is the February 2020 paper,²⁴ “Melatonin in Mitochondria: Mitigating Clear and Present Dangers,” published in the Physiology journal. It’s written by the best researcher in melatonin, Russel Reiter, Ph.D.

Reiter’s key finding is that 95% of the melatonin your body produces is made inside your mitochondria in response to near-infrared (IR) radiation from the sun or other near IR sources. Only 5% of melatonin is produced in your pineal gland.

Melatonin is a master hormone,²⁵ a potent antioxidant²⁶ and antioxidant recycler,²⁷ and a master regulator of inflammation and cell death.²⁸ These functions are part of what makes melatonin such an important anticancer molecule.²⁹

So, to produce melatonin inside your mitochondria actually makes perfect sense, as your mitochondria desperately need protection from the damage caused by oxidative stress produced in the electron transport chain.

In summary, your mitochondria produce ATP, the energy currency of your cells. A byproduct of this ATP production is reactive oxidative species (ROS), which are responsible for oxidative stress. Excessive amounts of ROS will damage your mitochondria, contributing to suboptimal health, inflammation and chronic health conditions such as diabetes, obesity and thrombosis (blood clots).

The good news is your body has a built-in way to counteract these ROS. Inside your mitochondria, you also have an antioxidant system, and the main antioxidant is melatonin.

Melatonin also upregulates your glutathione pathway, which is another potent antioxidant pathway shown to play an important role in COVID. Like vitamin D, glutathione deficiency is associated with COVID severity. In short, your body is well-designed to address oxidative stress, but you need sun exposure in order for that mechanism to work.

One aspect of sun exposure that Seheult did not mention was that it will also increase your testosterone levels naturally. Most people aren’t aware that the highest hormone concentration in men and women is testosterone. Obviously levels are far lower in women, but testosterone is higher than estrogen in women and it is important for optimal biological function — just one more reason why you want to aim for daily sun exposure on as much skin as possible.

Also remember it is not the sun that is the primary cause of sunburn and skin cancer: It is elevated linoleic acid (LA) in the seeds, nuts and seed oils you consume. LA should only be 1% to 2% of daily calories, and it is over 20% in most people. It takes years to lower your LA levels as it stays in your body for about seven years, so start eliminating it from your diet today.

Guidance for Oral Vitamin D Supplementation

If you do opt for oral supplementation, as an absolute last resort, there are additional considerations to take into account. For example, you need 244% more oral vitamin D if you’re not also taking magnesium and vitamin K2,³⁰ so these three should ideally be taken together. You can learn more about this in “Magnesium and K2 Optimize Your Vitamin D Supplementation.”

Remember, the most crucial factor when it comes to vitamin D is your blood level, not the dose, as the dose you need is dependent on several individual factors, including your baseline blood level. The level to shoot for is between 60 ng/mL and 80 ng/mL (150 nmol/L to 200 nmol/L); 40 ng/mL should be considered the low-end cutoff.

Before you start oral supplementation, you’ll want to get a baseline measurement. One of the easiest and most cost-effective ways of measuring your vitamin D level is to participate in the GrassrootsHealth’s personalized nutrition project, which includes a vitamin D testing kit.

Once you know what your blood level is, you can assess the dose needed to maintain or improve your level. The chart below can be helpful. Be sure to remeasure your vitamin D level in three to six months, to evaluate how your sun exposure and/or supplement dose is working for you, and adjust accordingly.

• ¹ Google Docs by Karl Pfleger, Ph.D., Meta Analyses List
• ^2, 10 Twitter Karl Pfleger August 11, 2022
• ^3, 4 J. Clin. Endcrinol. Metab. December 11, 2021; dgab892
• ^5, 6 Front. Public Health December 22, 2021; 9: 736665
• ⁷ Diabetes Metab. Res. Rev. May 2022; 38(4): e3517
• ^8, 9 PLOS ONE July 6, 2022; 17(7): e0268396
• ¹¹ Flgov.com December 17, 2021
• ¹² VitaminD4all.com December 7, 2020
• ^13, 14, 22 Nutrients October 31, 2020;12, 3361; DOI: 10.3390/nu12113361
• ¹⁵ Nutrients, 2020;12:988
• ¹⁶ Advances in Pharmacological Sciences 2018; 2018: 8494816
• ¹⁷ ATS Journals October 5, 2010; 183(10)
• ¹⁸ Medicina 2019 Sep; 55(9): 541
• ¹⁹ Diabetes.co.uk January 15, 2019
• ²⁰ The Lancet Diabetes & Endocrinology September 1, 2014; 2(9): 682-684
• ²¹ Current Treatment Options in Cardiovascular Medicine 2012 Aug; 14(4): 414–424
• ²³ Nutrients October 31, 2020;12, 3361; DOI: 10.3390/nu12113361, Table 3
• ²⁴ Physiology February 5, 2020 DOI: 10.1152/physiol.00034.2019
• ²⁵ Indian J. Exp Biol. May 1996; 34(5): 391-402
• ²⁶ Frontiers in Pharmacology August 21, 2020 DOI: 10.3389/fphar.2020.01220
• ²⁷ Allergy Research Group, Melatonin, the Antioxidant Recycler
• ²⁸ Cell Death & Disease 2019; 10 article number 317
• ²⁹ Oncotarget June 13, 2017; 8(24): 39896–39921
• ³⁰ GrassrootsHealth Magnesium and Vitamin K2 Combined Important for Vitamin D Levels