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.

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Splenda Side-Effects

On April Fool’s Day, 1998, the Food and Drug Administration approved the artificial sweetener sucralose, aka 1,6-dichloro-1,6-dideoxy-beta-D-fructofuranosyl-4- chloro-4-deoxy-alpha-D-galactopyranoside. But, despite its scary name, the worst it seemed to do was just be a rare migraine trigger in susceptible individuals, to which the manufacturer of sucralose replied that you have to weigh whatever risk there may be against its broader health benefits, “helping to mitigate the health risks associated with the national epidemic of obesity.”

As I discuss in my video Effect of Sucralose (Splenda) on the Microbiome, the hope was to offer a harmless sugar substitute to provide a sweet taste without the calories or spikes in blood sugar. However, that’s not how it appears to have turned out: Population studies have tied consumption of artificial sweeteners, mainly in diet sodas, with increased risk of developing obesity, metabolic syndrome, and type 2 diabetes. But, an association is not causation. You’ve got to put it to the test.

Indeed, if you give obese individuals the amount of sucralose found in a can of diet soda, for example, they get a significantly higher blood sugar spike in response to a sugar challenge, requiring significantly more insulin—20 percent higher insulin levels in the blood—suggesting sucralose causes insulin resistance. This may help explain the links between artificial sweetener consumption and the development of diabetes, heart disease, and stroke. So, sucralose is not some inert substance. It affects the blood sugar response. But how?

The Splenda company emphasizes that sucralose is hardly even absorbed into the body and, as such, stays in the digestive tract to be quickly eliminated from the body. But the fact that it’s not absorbed in the small intestine means it makes it down to the large intestine and may affect our gut flora. Studies have been done on artificial sweeteners and the gut bacteria of rats going back years, but there hadn’t been any human studies until fairly recently. Researchers tested saccharin, sucralose, and aspartame, the artificial sweeteners in Sweet & Low, Splenda, and NutraSweet, respectively, and found that non-caloric artificial sweeteners induce glucose intolerance by altering the microbes in our gut. The human studies were limited, but, after a few days on saccharin, for example, some people got exaggerated blood sugar responses tied to changes over just one week to the type of bacteria they had in their gut.

Acesulfame K, another common artificial sweetener, also was found subsequently to be associated with changes in gut bacteria. So, all this time, artificial sweeteners were meant to stave off chronic diseases but may actually be contributing to the problem due to microbial alterations. Some in the scientific community were surprised that “even minor concentrations of a sweetener [in this case, aspartame] are sufficient to cause substantial changes in gut inhabitants…” Others were less surprised. Each molecule of aspartame is, after all, metabolized into formaldehyde. That may explain why some people who are allergic to formaldehyde have such bad reactions to the stuff. “Therefore, it is not unexpected that very small amounts of the sweetener can modify bacterial communities…” However, the reports about the safety of aspartame are mixed. “All of the studies funded by the industry vouch for its safety, whereas 92% of independently funded studies report that aspartame can cause adverse health effects.”

That should tell you something.

“Undoubtedly, consumers of these food additives, which are otherwise perceived as safe, are unaware that these substances may influence their gut bacteria. This may be of particular importance to patients with diseases correlated with modifications of the gut [bacteria], such as irritable bowel syndrome and inflammatory bowel diseases” (IBDs) like ulcerative colitis and Crohn’s disease. People may not realize artificial sweeteners may be affecting their gut.

Might the effect be large enough to be actually see changes in the incidence of inflammatory bowel disease? Let’s look at Canada, the first country to approve the use of sucralose. Their rates of IBD did seem to double after the approval of sucralose. What about in the United States? After decades of relatively stable rates of ulcerative colitis and Crohn’s disease, rates did appear to start going up. In China, after the approval of sucralose, IBD rates rose 12-fold. Again, these could just be total flukes, but such correlations were also found on two other continents as well. Indeed, the more graphs you see showing this rise in rates of IBD after sucralose’s approval in different countries, the harder it is to dismiss a possible connection.

The good news, though, is that after stopping artificial sweeteners, the original balance of gut bacteria may be restored within weeks. Now, of course, the negative consequences of artificial sweeteners should not be interpreted to suggest that we should all go back to sugar and high fructose corn syrup. For optimal health, it is recommended that we all try to cut down on both.

Can’t get enough of artificial sweeteners? Check out:

Erythritol May Be a Sweet Antioxidant, but there are some caveats for it and other nontoxic, low-calorie sweeteners. See:

Does it really matter if our gut flora get disrupted? You’re in for a surprise. 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, year-in-review presentations: