Vitamin D Supplements for Reducing Cancer Mortality

It all started with a famous study entitled “Do sunlight and vitamin D reduce the likelihood of colon cancer?” that was published in 1980. Johns Hopkins University researchers were trying to figure out why states like New Mexico and Arizona have only about half the colon cancer rates of states like New York, New Hampshire, and Vermont. Could it be because New Mexicans and Arizonans get so much more sun? The researchers proposed that perhaps vitamin D, known as the sunshine vitamin, is a protective factor against colon cancer. Since then, sun exposure has also been associated with lower rates of 14 other types of cancer.

As I discuss in my video Do Vitamin D Supplements Reduce the Risk of Dying from Cancer?, vitamin D may also affect cancer survival. Higher blood levels of vitamin D were associated with lower mortality of patients with colorectal cancer. How much lower? Nearly half the mortality. And, the higher the vitamin D levels, the lower the death rate appeared to fall. This may explain why the survival rate from colon cancer may depend in part “on the season of diagnosis.” The risk of rapid death is lowest if you’re diagnosed in the fall after you’ve spent the summer building up your vitamin D stores. Other risk factors could be seasonal, too. For example, perhaps people are taking advantage of the fall harvest and eating healthier, which might explain lower risk in the autumn. Additionally, “[a]lcohol intake is a risk factor and may be highest in the winter season…” What about physical activity? In the summer, we may be more likely to be outside running around, not only getting more sun, but also getting more exercise, which may itself be protective.

These kinds of studies just provide circumstantial evidence. Establishing a cause-and-effect relationship between colon cancer and vitamin D deficiency using observational studies is challenging because of confounding factors, such as exercise habits—so-called lurking variables. For example, there may be a tight correlation between ice cream sales and drowning deaths, but that doesn’t mean ice cream causes drowning. A more likely explanation is that there is a lurking third variable, like hot weather in summertime, that explains why drowning deaths are highest when ice cream consumption is also at its highest.

This actually happened with hormone replacement therapy. Women taking drugs like Premarin appeared to have 50 percent less risk of heart disease, so doctors prescribed it to women by the millions. But, if we dig a little deeper into the data, we find that, indeed, women taking estrogen had 50 percent lower risk of dying from heart disease, but they also had a 50 percent lower risk of dying from accidents and homicide, so it probably wasn’t the drug. The only way to know for sure is to put it to the test in a randomized, clinical trial, where half the women are given the drug and we see what happens. A decade later, such a study was done. Instead of having a 50 percent drop in risk, within a year of being given the hormone pills, heart attack and death rates shot up 50 percent. In retrospect, the lurking variable was likely socioeconomic class. Poor women are less likely to be prescribed hormone replacement therapy and more likely to be murdered and die of heart disease. Because of the lurking variable, a drug we now know to be dangerous had initially appeared to be protective.

Besides lurking variables, there’s also the possibility of reverse causation. Perhaps low vitamin D levels didn’t worsen the cancer. Instead, maybe the cancer worsened the vitamin D levels. This may be unlikely, since tumors don’t appear to directly affect vitamin D levels, but cancer treatment might. Even simple knee surgery can cause vitamin D levels to drop dramatically within hours, thought to be due simply to the inflammatory insult of cutting into someone. So, maybe that could help explain the link between lower vitamin D and lower survival. And, cancer patients may be spending less time running around the beach. So, yes: Higher vitamin D levels are associated with improved survival in colorectal cancer, and the same has been found for breast cancer. In fact, there is about double the risk of breast cancer recurrence and death in women with the lowest vitamin D levels. What’s more, higher vitamin D levels are associated with longer survival with ovarian cancer, as well as having better outcomes for other cancers like lymphoma. But, the bottom-line, as we learned with hormone replacement, is that we have to put it to the test. There weren’t a lot of randomized controlled trials on vitamin D supplements and cancer, however…until now.

We now have a few randomized controlled trials, and vitamin D supplements do indeed appear to reduce the risk of dying from cancer! What dose? Researchers suggest getting blood levels up to at least about 75 nanomoles per liter. These levels are not reached by as many as three-quarters of women with breast cancer nor achieved by a striking 97 percent of colon cancer patients .

Getting up to these kinds of levels—75 or, perhaps even better, 100 nanomoles—might require about 2000 to 4000 IU of vitamin D a day, levels of intake for which there appear to be no credible evidence of harm. Regardless of what the exact level is, the findings of these kinds of studies may have a profound influence on future cancer treatment.


What about just getting sun instead? Be sure to check out my six-part video series:

It’s better, of course, to prevent colon cancer in the first place. See, for example:

For more on that extraordinary story about Premarin and hormone replacement therapy, see How Did Doctors Not Know About the Risks of Hormone Therapy?

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Vegans Should Consider Taking DHA Supplements

We are all fatheads.

Indeed, about half the dry weight of our brain is fat. Lower levels of the long-chain omega-3 fat DHA in some areas of Alzheimer’s brains got people thinking that perhaps DHA is protective. Since the level of DHA in the brain tends to correlate with the level of DHA in the blood, cross-sectional studies of dementia and pre-dementia patients have been done. The result? The dementia and pre-dementia subjects do tend to have lower levels of both long-chain omega-3s, EPA and DHA, circulating in their bloodstream. This doesn’t necessarily mean that lower omega-3 levels cause cognitive impairment, however. It was just a snapshot in time, so we don’t know which came first. As I discuss in my video Should Vegans Take DHA to Preserve Brain Function?, maybe the dementia led to a dietary deficiency, rather than a dietary deficiency leading to dementia.

What we need is to measure long-chain omega-3 levels at the beginning and then follow people over time, and, indeed, there may be a slower rate of cognitive decline in those who start out with higher levels. We can actually see the difference on MRI. Thousands of older men and women had their levels checked and were scanned and then re-scanned. The brains of those with higher levels looked noticeably healthier five years later.

The size of our brain actually shrinks as we get older, starting around age 20. Between ages 16 and 80, our brain loses about 1 percent of its volume every two to three years, such that by the time we’re in our 70s, our brain has lost 26 percent of its size and ends up smaller than that of 2- to 3-year-old children.

As we age, our ability to make long-chain omega-3s like DHA from short-chain omega-3s in plant foods, such as flaxseeds, chia seeds, walnuts, and greens, may decline. Researchers compared DHA levels to brain volumes in the famed Framingham Study and found that lower DHA levels were associated with smaller brain volumes, but this was just from a snapshot in time, so more information was needed. A subsequent study was published that found that higher EPA and DHA levels correlated with larger brain volume eight years later. While normal aging results in overall brain shrinkage, having lower levels of long-chain omega-3s may signal increased risk. The only thing we’d now need to prove cause and effect is a randomized controlled trial showing we can actually slow brain loss by giving people extra long-chain omega-3s, but the trials to date showed no cognitive benefits from supplementation…until now.

A “double-blind randomized interventional study provide[d] first-time evidence that [extra long-chain omega-3s] exert positive effects on brain functions in healthy older adults,” a significant improvement in executive function after six and a half months of supplementation, and significantly less brain shrinkage compared to placebo. This kind of gray matter shrinkage in the placebo might be considered just normal brain aging, but it was significantly slowed in the supplementation group. The researchers also described changes in the white matter of the brain, increased fractional anisotropy, and decreases in mean and radial diffusivity—terms I’ve never heard before but evidently imply greater structural integrity.

So, we know that having sufficient long-chain omega-3s EPA and DHA may be important for preserving brain function and structure, but what’s “sufficient” and how do we get there? The Framingham Study found what appears to be a threshold value around an omega-3 index of 4.4, which is a measure of our EPA and DHA levels. Having more or much more than 4.4 didn’t seem to matter, but having less was associated with accelerated brain loss equivalent to about an extra two years of brain aging, which comes out to about a teaspoon less of brain matter, so it’s probably good to have an omega-3 index over 4.4.

The problem is that people who don’t eat fish may be under 4.4. Nearly two-thirds of vegans may fall below 4.0, suggesting a substantial number of vegans have an omega-3 status associated with accelerated brain aging. The average American just exceeds the threshold at about 4.5, though if we age- and gender-match with the vegans, ironically, the omnivores do just as bad. There aren’t a lot of long-chain omega-3s in Big Macs either, but having a nutrient status no worse than those eating the Standard American Diet is not saying much.

What we need is a study that gives those with such low levels some pollutant-free EPA and DHA, and then sees how much it takes to push people past the threshold…and here we go: Phase 2 of the study gave algae-derived EPA and DHA to those eating vegan diets with levels under 4.0. About 250mg a day took them from an average of 3.1 over the threshold to 4.8 within four months. This is why I recommend everyone consider eating a plant-based diet along with contaminant-free EPA and DHA to get the best of both worlds—omega-3 levels associated with brain preservation while minimizing exposure to toxic pollutants.


A list of my recommendations can be found here: Optimum Nutrition Recommendations.

Why not just eat fish or take fish oil? I explain why in these videos:

How else can we protect our brains? See, for example:

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Do DHA Supplements Improve Brain Function?

The concept of vitamins was first described by none other than Dr. Funk. In his landmark paper in 1912, he discussed the notion that there were complex compounds our body couldn’t make from scratch, so we had to get them from our diet. By the mid-20th century, all the vitamins had been discovered and isolated, but it wasn’t until the 1960s that we realized that certain fats were essential, too.

In 1929, the necessity for fat was definitively settled… “in the diet (of the rat),” but when one of the researchers tried a 99 percent fat-free diet on himself for six months, ironically, he felt better. His high blood pressure went away, he felt more energetic, and his migraines disappeared. This one-man experiment “fortif[ied] the medical profession’s doubt that essential fatty acids had any relevance to humans,” until TPN—Total Parenteral Nutrition, meaning feeding someone exclusively through an IV—was developed in the 1960s. TPN was initially developed for babies born without working intestines. Because we didn’t think humans needed fat, “the first preparations were fat free, and they rapidly induced severe EFA [essential fatty acid] deficiencies, ultimately convincing the medical community” that some fats are indeed essential. They started out using safflower oil, but, as they discovered in a young girl given the oil after an abdominal gunshot wound, we don’t just need fat—we need specific fats like omega-3s. So, when they switched from safflower oil to soybean oil, she was restored to normal.

The fact it took so long and under such extreme circumstances to demonstrate the essential nature of omega-3s illustrates how hard it is to develop overt omega-3 deficiency. Of course, the amount required to avoid deficiency is not necessarily the optimal amount for health. The vitamin C in a spoonful of orange juice would be enough to avoid scurvy (the overt vitamin C deficiency disease), but no one considers that enough vitamin C for optimal health.

As I discuss in my video Should We Take DHA Supplements to Boost Brain Function?, what would optimal omega-3 status look like? Well, doubt has been cast on its role in heart health (see Is Fish Oil Just Snake Oil?), which appears to have been based on a faulty premise in the first place (see Omega-3s and the Eskimo Fish Tale), so taking extra omega-3s for our heart might not make any sense (see Should We Take EPA and DHA Omega-3 for Our Heart?). But what about for our baby’s brain (see Should Pregnant and Breastfeeding Women Take DHA?)? Extra DHA may not help pregnant or breast-feeding fish-eaters, but those who want to avoid the contaminants in fishes can take supplements of pollutant-free algae oil to get the best of both worlds for their babies (see Should Vegan Women Supplement with DHA During Pregnancy?). What about adults? There doesn’t appear to be any apparent psychological (see Fish Consumption and Suicide) or neurological (see Is Fish “Brain Food” for Older Adults?) benefit of DHA supplementation for the general public, but what about in those who don’t eat fish?

The famous Alpha Omega Trial randomized thousands of people over three years to get either long-chain omega-3s from fish, short-chain omega-3s from plants, or placebo. The result? The study found no significant benefits for any kind of omega-3 supplementation on global cognitive decline. However, most of the subjects were eating fish, thereby already getting pre-formed DHA in their diets. General population studies like this, that find no benefit, can’t fully inform us about the role of DHA in brain health. It would be akin to giving half these people oranges, finding no difference in scurvy rates (zero in both groups), and concluding vitamin C plays no role in scurvy.

In 2013, for the first time, DHA supplementation was found to improve memory and reaction time among young adults who rarely ate fish. Previous randomized, controlled trials failed to find such a benefit among18- to 45-year-olds, but they only lasted a few months at most, whereas the 2013 study lasted for six months. If all the studies showed either no effect or a positive effect, one might give it a try. But in one of those shorter trials, DHA supplementation didn’t just fail to show benefit—it appeared to make things worse. After 50 days, those who consumed the DHA had worse memory than those taking the placebo. So, out of the six randomized controlled trials for DHA supplementation, four showed nothing, one showed a benefit, and one showed a harm. If it were just about boosting brain function in the short term, I’d err on the side of caution and spend my money elsewhere.


What about the long term though? See Should Vegans Take DHA to Preserve Brain Function?.

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations: