Does Aspartame Cause Lymphoma?

The approval of aspartame has a controversial history. The Commissioner of the U.S. Food and Drug Administration (FDA) concluded that “there is a reasonable certainty that human consumption of aspartame: (1) …will not pose a risk of brain damage resulting in mental retardation, endocrine [hormonal] dysfunction, or both; and (2) will not cause brain tumors.” However, the FDA’s own Public Board of Inquiry withdrew their approval over cancer concerns. “Further, several FDA scientists advised against the approval of aspartame, citing…[the aspartame company’s] own brain tumor tests…” Regardless, the Commissioner approved aspartame before he left the FDA and went on to enjoy a thousand-dollar-a-day consultancy position with the aspartame company’s PR firm. Then, the FDA actually prevented the National Toxicology Program (NTP) from doing further cancer testing. As I discuss in my video Does Aspartame Cause Cancer? we were then left with people battling over different rodent studies, some of which showed increased cancer risk, while others didn’t.

This reminds me of the saccharin story. That artificial sweetener caused bladder cancer in rats but not mice, leaving us “to determine whether humans are like the rat or like the mouse.” Clearly, we had to put the aspartame question to the test in people, but the longest human safety study lasted only 18 weeks. We needed better human data.

Since the largest rat study highlighted lymphomas and leukemias, the NIH-AARP study tracked blood cancer diagnoses and found that “[h]igher levels of aspartame intake were not associated with the risk of…cancer.” Although the NIH-AARP study was massive, it was criticized for only evaluating relatively short-term exposure. Indeed, people were only studied for five years, which is certainly better than 18 weeks, but how about 18 years?

All eyes turned to Harvard, where researchers had started following the health and diets of medical professionals before aspartame had even entered the market. “In the most comprehensive long-term [population] study…to evaluate the association between aspartame intake and cancer risk in humans,” they found a “positive association between diet soda and total aspartame intake and risks of [non-Hodgkin’s lymphoma] and multiple myeloma in men and leukemia in both men and women,” as you can see at 2:12 in my video. Why more cancer in men than women? A similar result was found for pancreatic cancer and diet soda, but not soda in general. In fact, the only sugar tied to pancreatic cancer risk was the milk sugar, lactose. The male/female discrepancy could have simply been a statistical fluke, but the researchers decided to dig a little deeper.

Aspartame is broken down into methanol, which is turned into formaldehyde, “a documented human carcinogen,” by the enzyme alcohol dehydrogenase.The same enzyme that detoxifies regular alcohol is the very same enzyme that converts methanol to formaldehyde. Is it possible men just have higher levels of this enzyme than women? Yes, which is why women get higher blood alcohol levels than men drinking the same amount of alcohol. If you look at liver samples from men and women, you can see significantly greater enzyme activity in the men, so perhaps the higher conversion rates from aspartame to formaldehyde explain the increased cancer risk in men? How do we test this?

Ethanol—regular alcohol—competes with methanol for this same enzyme’s attention. In fact, regular alcohol is actually “used as an antidote for methanol poisoning.” So, if this formaldehyde theory is correct, men who don’t drink alcohol or drink very little may have higher formaldehyde conversion rates from aspartame. And, indeed, consistent with this line of reasoning, the men who drank the least amounts of alcohol appeared to have the greatest cancer risk from aspartame.

A third cohort study has since been published and found no increased lymphoma risk associated with diet soda during a ten-year follow-up period. So, no risk was detected in the 18-week study, the 5-year study, or the 10-year study—only in the 18-year study. What should we make of all this?

Some have called for a re-evaluation of the safety of aspartame. The horse is kind of out of the barn at this point with 34 million pounds of aspartame produced annually, but that doesn’t mean we have to eat it, especially, perhaps, pregnant women and children.


For more information on the effects of aspartame, watch my videos Aspartame and the Brain and Aspartame-Induced Fibromyalgia. Interested in learning more about the effects of consuming diet soda? See, for example:

What about Splenda? Or monk fruit sweetener? I have videos on those, too—watch Effect of Sucralose (Splenda) on the Microbiome and Is Monk Fruit Sweetener Safe?.

I also do a comparison of the most popular sweeteners on the market, including stevia and xylitol, in my video A Harmless Artificial Sweetener.

Perhaps the best candidate is erythritol, which you can learn about in my video Erythritol May Be a Sweet Antioxidant. That said, it’s probably better if we get away from all intense sweeteners, artificial or not. See my video Unsweetening the Diet for more on this.

In health,
Michael Greger, M.D.

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

The Foods With the Highest Aspirin Content

The results of a recent aspirin meta-analyses suggesting a reduction of cancer mortality by about one-third in subjects taking daily low-dose aspirin “can justly be called astounding.” Yet the protection from “Western” cancers enjoyed by those eating more traditional plant-centered diets, such as the Japanese, “is even more dramatic.” I examine this in my video Plants with Aspirin Aspirations.

Before the Westernization of their diets, animal products made up only about 5 percent or less of the Japanese diet. At 0:37 in my video, you can see the difference in cancer mortality of U.S. men and women compared with Japanese men and women. “[A]ge-adjusted death rates from cancers of the colon, prostate, breast, and ovary were on the order of 5–10-fold lower in Japan than in the US at that time; mortality from pancreatic cancer, leukemias, and lymphomas was 3–4-fold lower in Japan. But this phenomenon was by no means isolated to Japan; Western cancers were likewise comparatively rare in other societies where “people ate plant-based diets.”

“The cancer protection afforded by lifelong consumption of a plant-based diet, in conjunction with leanness and insulin sensitivity (which tend to be promoted by low-fat plant-based diets)…may be very substantial indeed.” Therefore, a “lifestyle protocol for minimizing cancer risk” may include a whole-food plant-based diet.

If part of this cancer protection arises out of the aspirin phytonutrients in plants, are there any plants in particular that are packed with salicylates? Though salicylic acid, the main active ingredient in aspirin, is “ubiquitously present in fruits and vegetables,” the highest concentrations are found in herbs and spices.

Red chili powder, paprika, and turmeric contain a lot of salicylates, but cumin is about 1 percent aspirin by weight. Eating a teaspoon of cumin is like taking a baby aspirin. (See the table at 1:54 in my video for details on other herbs and spices, and their salicylate content.) “Consequently, populations that incorporate substantial amounts of spices in foods may have markedly higher daily intakes of salicylates. Indeed, it has been suggested that the low incidence of colorectal cancer among Indian populations may be ascribed in part to high exposure to dietary salicylates throughout life from spice consumption.”

“The population of rural India, with an incidence of colorectal cancer which is one of the lowest in the world, has a diet that could be extremely rich in salicylic acid. It contains substantial amounts of fruits, vegetables, and cereals flavored with large quantities of herbs and spices.” Some have proposed it’s the curcumin in the spice turmeric (which I discuss in detail in my video Turmeric Curcumin and Colon Cancer), but it may be the salicylic acid in cumin—and the spicier the better.

A spicy vegetable vindaloo may have four times the salicylates of a milder Madras-style veggie dish. As you can see from the chart at 2:55 in my video, after just one meal, we get an aspirin spike in our bloodstream like we just took an aspirin. So, eating flavor-filled vegetarian meals, with herbs and spices, may be more chemoprotective—that is, more protective against cancer—than regular, blander vegetarian meals.

We may also want to eat organic produce. “Because salicylic acid is a defense hormone of plants, the concentration…is increased when plants become stressed,” like when they are bitten by bugs (unlike pesticide-laden plants). Indeed, soups made from organic vegetables were found to have nearly six times more salicylic acid than soups prepared from conventionally grown ingredients.

We should also choose whole foods. Whole-grain breads, which are high in salicylic acid, contain about 100 times more phytochemicals than white bread: 800 phytochemicals compared to 8.

“Interest in the potential beneficial effects of dietary salicylates has arisen, in part, because of the extensive literature on the disease-preventative effects of Aspirin™. However, it should not be forgotten that plant products found to contain salicylic acid are generally rich sources of other phenolic acids…[and many] also have a marked anti-inflammatory and redox-related bioactivity [that is, antioxidant activity] in mammalian cells. Their potential protective effects should not be overlooked. In this context, the importance of dietary salicylic acid should not perhaps be over emphasised…Indeed, some believe that ‘salicylic acid deficiency’ has important public health implications and that it should be classed as an essential vitamin, namely ‘Vitamin S’.”

What they’re saying is that we should all eat a lot of plants.


If you missed the first two videos in this series, see Should We All Take Aspirin to Prevent Heart Disease? and Should We All Take Aspirin to Prevent Cancer?.

The drug-like anti-inflammatory power of certain plant foods may make them a risky proposition during pregnancy. See Caution: Anti-Inflammatory Foods in the Third Trimester.

Herbs and spices not only have some of the most anti-inflammatory properties, but they also are well-rounded protectants. See:

In health,
Michael Greger, M.D.

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

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: