Is it possible that vitamin D can ward off cancer, cardiovascular diseases, diabetes, metabolic disorders, depression, infectious diseases, autoimmune diseases, mortality and even autism? Readers of health articles have been deluged by such stories. Researchers are spending time and millions of dollars to explore vitamin D. A search on PubMed (a massive on-line bibliography of articles published in medical journals) for vitamin D finds more than 20,000 studies within the past five years alone.
In response, some people are boosting their vitamin D intake above the recommended dietary allowance, hoping to maximize supposed benefits. Could too much vitamin D create bad side effects or lead to adverse events?
Can increasing the intake above the current recommended dietary allowance really cure or prevent other health conditions?
Vitamin D is really a hormone.
Vitamin D is actually a pro-hormone that is involved in many metabolic processes. Your body makes vitamin D from sunlight on your skin. You can also take supplements and you can get a small amount from fortified food sources such as milk or orange juice.
Supplements come in two formats: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D2 is found in sun-exposed mushrooms. Vitamin D3 is the form made naturally in human skin and is made from a cholesterol precursor obtained from lanolin. It can be found in oil-rich fish like salmon, mackerel and herring. There is some evidence that the D3 format is more effective in raising levels of vitamin D in the body as compared to vitamin D2. Vitamin D is fat-soluble, meaning that if you take more than your body can immediately use, the excess is stored in your body and is not excreted in urine (as many vitamins are).
In your body, your liver converts vitamin D from sunlight or supplements to 25-hydroxyvitamin D [25(OH)D], the form that’s measured in a blood test. (In this article, when we refer to blood levels of vitamin D, this is what we mean.) The 25(OH)D is then converted again, mostly in the kidneys, to the activated form of vitamin D, a hormone called calcitriol (1,25-dihydroxyvitamin D).
It’s plausible that vitamin D may play a role in a host of other diseases and conditions such as cancer, cardiovascular disease and diabetes, because there are calcitriol receptors on nearly all tissues in the body. Calcitriol plays a role in regulation of more than 900 different genes. In cell culture and animal studies, researchers have found that calcitriol is involved in cell differentiation, proliferation and inhibition, inflammation, and the synthesis and secretion of insulin. Calcitriol also has an impact on brain function and development. Two US researchers proposed a mechanism to explain how calcitriol may be involved in the regulation of the production of serotonin, a brain chemical that is often out of balance in autistic children.
At first blush, it may seem hard to believe that vitamin D could be associated with so many different conditions. However, John J. Cannell, MD, founder and executive director of the Vitamin D Council, says, “Many people are turned off by these claims and say it’s impossible that one thing is involved in so many different disease processes, but they are unaware of the mechanism of vitamin D. It is actually a steroid hormone precursor that turns genes on and off. There are at least a thousand genes that are directly regulated by vitamin D.”
Recent Vitamin D Studies
Here are some examples of studies that found a link between vitamin D and health conditions. Keep in mind, many times doctors find that vitamin D is low in a patient with a particular condition — RA or bone density, for example. Research is having a difficult time proving which came first: Did the low vitamin D cause the condition or did the condition cause the low vitamin D? Put simply, a person suffering from the pain of RA is less likely to spend time outside absorbing the sunlight needed to produce the hormone vitamin D.
Vitamin D and Bone Health
Vitamin D was originally thought to be good for maintaining bone health; however, a new study from the Lancet is casting doubt that there are bone benefits after all. An analysis of 81 studies involving more than 53,000 adults took vitamin D supplements to observe how effective they might be in boosting bone mineral density and preventing falls and fractures. Results also showed that the dosage present in the supplements did not make a difference.
This meta-analysis echoes the results of another one published in December 2017 that examined vitamin D plus calcium supplements and bone fractures in the elderly. The study involved 33 trials with more than 51,000 participants.
Cholesterol and Vitamin D
Vitamin D may improve cholesterol numbers.
A recent study analyzed data from 576 postmenopausal women who were part of the National Institutes of Health’s Women’s Health Initiative trial. Women who took 400 IU of vitamin D plus 1,000 mg of calcium daily showed a significantly higher blood level of vitamin D after two years, compared to a control group that took a placebo. Interestingly, those who had higher blood levels of vitamin D also had better lipid profiles, showing increased high-density (“good”) cholesterol, decreased low-density (“bad”) cholesterol and lower triglycerides. The researchers acknowledge that the sample size was small and their findings are not conclusive about how vitamin D affects cardiovascular health. However, given that these results were from blood work for women followed for several years, there is a relationship here that merits further research. The study was published in the March 2014 issue of Menopause.
Heart Disease, Cancer and Vitamin D
Experts were hoping a comprehensive trial just completed called VITAL (VITamin D and OmegA-3TriaL) would reveal health benefits of vitamin D. Dr. Manson was the lead investigator for this large-scale US study among 10,000 adult women over 55 and 10,000 men over 50. She and her colleague, Julie Buring, DSc, investigated if taking daily doses of 2,000 IU of vitamin D or a supplement of omega-3 fatty acids (Omacor fish oil, 1 gram) could reduce the risk of developing cancer, heart disease and stroke in healthy people with no history of these diseases.
The trial ended in 2018 and revealed that supplementation with 1 g/day of n-3 fatty acid or a dose of 2,000 IU/day did not prove to be effective for prevention of cardiovascular disease or cancer among middle-aged men and women after a five-year follow-up.
Breast Cancer and Vitamin D
Patients with higher levels of vitamin D at the time of breast cancer diagnosis may live longer.
A randomized trial with 15,646 women from the Women’s Health Initiative sought to see if higher vitamin D levels could reduce the incidence of breast cancer. Of the participants, 57% took 400 IU/d of vitamin D3 along with 1,500 mg/d of calcium, while 43% did not take either. The supplements were given at random. Ca+D was proven to reduce the risk of total, breast and invasive breast cancers by 14-20%. The study was published in the February 2018 issue of Anticancer Research.
Arthritis and Vitamin D
Studies show it may slow progression, but is not yet proven.
Dawn Hunter, a freelance editor based in Toronto, Ontario, takes 2,000 IU of vitamin D daily, even though some health guidelines call for a much smaller dose of 600 IU per day. “Every time I stop taking it, my levels just plummet,” says Hunter, who has arthritis and says that she does not have the opportunity to get much natural sunshine.
Five years ago, Hunter found out she was severely deficient after her rheumatologist ordered a blood test. She addressed her deficiency by taking 4,000 IU daily for a year to boost her blood level from 14.8 ng/mL (nanograms per milliliter) and has been maintaining her level at 30.4 ng/mL with a daily dose of 2,000 IU for the past four years. (The normal range is 30.0 to 74.0 ng/mL.)
“When my vitamin D level increased, I noticed a small reduction in the general ache I had with my arthritis,” notes Hunter. “My rheumatologist says there is some evidence that arthritis can progress faster in people who have low levels of vitamin D. I was just turning 40 when my arthritis was diagnosed, so managing progression is important to me.”
Research published in May 2019 has shown rheumatoid arthritis (RA) to be an autoimmune disorder that takes form in a painful and achy feeling in different parts of the body. It is a complex disorder caused by both genetic and environmental factors. Vitamin D is a molecule that aids in the maintaining and signaling of calcium and phosphate homeostasis, two huge factors of RA. Therefore, low levels of vitamin D are shown to be related to higher risk of RA. There are many ongoing studies surrounding the impact of plasma vitamin D (within the blood) and the effect on slowing RA. However, while it works for some, it is not proven yet.
Autism and Vitamin D
Vitamin D may play a role in abnormal social behavior seen in people with autism spectrum disorder.
Rhonda Patrick, PhD, and Bruce Ames, PhD, at the Children’s Hospital Oakland Research Institute (CHORI) in California, proposed a causal mechanism for how three brain hormones that influence social behavior — serotonin, oxytocin and vasopressin — are activated by vitamin D at the genetic level. These brain hormones are often out of balance in children with autism spectrum disorder. These researchers hypothesize that the drop in adequate levels of vitamin D in the US over the past few decades — due in part to increased use of sunscreens and more indoor work — may in part explain the increase in autism rates.
Vitamin D may be a key factor in improving the symptoms of autistic children due to its role in regulating the genes active in brain development, neurotransmission (communication between neurons in the brain) and synaptic plasticity (the ability of the brain to learn and retain new information). The Association for Child and Adolescent Mental Health conducted a double-blind clinical trial spanning four months involving 109 autistic children between the ages of three and 10. The trial’s setup aimed to assess the impact that vitamin D has on the core symptoms of autism. In the study, there were 85 boys and 24 girls. Half received a vitamin D3 supplement of no more than 5,000 IU/day, while the other half received a placebo. The vitamin D blood levels were measured at the beginning and end of the trial. Severity of autism and social maturity were measured using the Childhood Autism Rating Scale, Aberrant Behavior Checklist, Social Responsiveness Scale and the Autism Treatment Evaluation Checklist. Symptoms greatly improved in the group that received vitamin D supplementation, while no changes were noted in the placebo group. Although the results are very promising, this is the first double-blind study assessing the efficacy of vitamin D in autistic children. The study was published in the January 2018 issue of the Journal of Child Psychology and Psychiatry.
Risk of Mortality and Vitamin D
Low vitamin D levels carry a greater risk of death.
In a large systematic review and meta-analysis published in the April 2014 issue of the British Medical Journal, researchers looked at the link between vitamin D and cardiovascular disease to assess mortality risk. Vitamin D blood levels were measured in 4,114 patients said to have had angina pectoris, better known as chest pain. Low blood levels of vitamin D were associated with a greater risk of death from cardiovascular disease, cancer and other causes. Calculations showed that in participants with 25(OH)D concentrations below 42.5 nmol/L had a greater risk of mortality and that supplementation with vitamin D3 at an ideal level (50 nmol/L) can maximize the benefits and reduce mortality.
However, in a 2018 study following 25,871 people age 50 and over for five years, the data shows that there is not a decrease in cardiovascular events or cancer incidence. Secondary findings did show a 28% decrease in heart attacks when using fish oil supplements as well as fewer deaths from cancer.
Different Views On The Ideal Level of Vitamin D?
How much vitamin D do lifeguards and roofers and hunter-gatherers from modern-day Tanzania have?
Almost 70% of the US population has insufficient levels of vitamin D when defined as less than 30 ng/mL, according to data combined from many studies. The level of vitamin D in your body is checked by a blood test that measures 25-hydroxyvitamin D [25(OH)D], the form of vitamin D that your body makes after converting what you receive from sunlight on skin, supplements or from some food sources, such as fortified milk and orange juice or from the flesh of fatty fish, including salmon, tuna and mackerel. The Vitamin D Council, a nonprofit organization based in California that works to educate the public about vitamin D, notes that there are several factors that affect how much vitamin D your body produces when your skin is exposed to sunlight. These factors include the time of year and time of day of exposure, where you live and the type of skin you have. You can request a blood test to check your vitamin D levels from your doctor, and the cost is usually covered in the US if a doctor orders it with the right diagnostic code.
According to the IOM (Institute of Medicine), the current recommended dietary intake of 600-800 IU for adults under the age of 70 and 800-1,000 IU for adults over 70 is sufficient to meet the needs of 97.5% of healthy adults who have minimal sun exposure. The IOM defines sufficiency of 25(OH)D as greater than 20 ng/mL. This recommendation was based on proven benefits for bone health, as the IOM did not find convincing evidence about causal outcomes with other health conditions.
The Vitamin D Council recommends a much higher daily intake of 5,000 IU to achieve a sufficiency level of 50 ng/mL. Dr. Cannell says, “The Vitamin D Council arrived at a recommendation very simply — to reproduce natural vitamin D from sun exposure. We know that natural vitamin D levels for lifeguards and roofers and hunter-gatherers from modern-day Tanzania are about 50 ng/mL. Until all the studies are done and all the science is completed, the safest thing for you to do is to maintain a natural vitamin D level.”
The IOM, however, noted a concern for attaining levels above 50 ng/mL and designated 4,000 IU daily as the tolerable upper intake limit, with the caution that this is not to be interpreted as a target intake level. JoAnn E. Manson, MD, DrPH, chief of preventive medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, was on the IOM Committee that developed the guidelines. She says, “There’s still a pretty wide range of intake in the IOM guidelines. The recommended dietary allowance is what will meet the requirements for a very large majority of the population, 97.5% in the US and Canada, but the IOM is also saying that there is a risk of adverse events at intake levels above 4,000 IU per day.”
Risks of Too Much Vitamin D
How much is too much?
Observational studies suggest that shooting for blood levels above 50 ng/mL may be associated with an increased risk of pancreatic cancer, cardiovascular disease and an increased risk of death. Dr. Manson says, “Some vitamin D is good, but more is not necessarily better. People should understand that there is limited research on long-term intakes above 2,000 IU daily. If they are regularly taking 3,000-4,000 IU per day, even if those levels may not have been linked to adverse events, we do not know if the benefits outweigh the risks long-term because we don’t have the evidence.”
Massive doses of 10,000 IU or more daily of vitamin D can put you at risk of developing high calcium levels in the blood or urine, which could cause calcification of blood vessels, kidney problems and kidney stones, especially if calcium intake is also high.
Dr. Manson advises that it’s important to distinguish between public health guidelines and medical situations where individual patients actually need more vitamin D, such as those who have bone health problems, malabsorption or who are on medications that may interfere with the metabolism of vitamin D. For example, steroid drugs like prednisone, weight loss drugs like Alli (orlistat) and the cholesterol-lowering drug Questran (cholestyramine) can reduce the absorption of vitamin D.
The National Institutes of Health (NIH) identifies a number of interactions of moderate concern, including with the cholesterol-lowering statin Lipitor: “Atorvastatin (Lipitor): Vitamin D might decrease the amount of atorvastatin (Lipitor) that enters the body. This might decrease how well atorvastatin (Lipitor) works.”
While there may be some situations that warrant higher doses of vitamin D, Dr. Manson cautions against taking megadoses of the “sunshine” vitamin. “Clinicians still have latitude to make individualized recommendations for higher amounts for their patients, but the public health guidelines are saying that most of the population should not be taking high doses or getting blood screening tests regularly because there is no evidence to support that,” says Dr. Manson
New Evidence On The Horizon
Right now, the excitement about vitamin D is focused on the promise it offers in helping with a host of health conditions beyond bone health. “The enthusiasm is definitely outpacing the evidence,” notes Dr. Manson. “Although we know that vitamin D deficiency needs treatment, there is a disconnect between the observational studies that have linked low vitamin D to nearly every known health condition and the randomized trials of high-dose vitamin D supplements that have been largely disappointing to date. We do need more large-scale randomized trials, though, to test rigorously whether supplementation above the recommended dietary allowance confers greater health benefits.”
***updated from 2017-18