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:

Why Drinking Diet Soda Makes You Crave Sugar

Recommendations on limiting sugar consumption vary around the world, with guidelines ranging from “[l]imit sweet desserts to one every other day” to “[k]eep sugar consumption to 4 or less occasions per day.” In the United States, the American Heart Association is leading the charge, “proposing dramatic reductions in the consumption of soft drinks and other sweetened products” and recommending fewer than about 5 percent of calories a day from added sugars, which may not even allow for a single can of soda.

Why is the American Heart Association so concerned about sugar? “Overconsumption of added sugars has long been associated with an increased risk of cardiovascular disease,” meaning heart disease and strokes. We used to think added sugars were just a marker for an unhealthy diet. At fast-food restaurants, for example, people may be more likely to order a cheeseburger with their super-sized soda than a salad. However, the new thinking is that the added sugars in processed foods and drinks may be independent risk factors in and of themselves. Indeed, worse than just empty calories, they may be actively disease-promoting calories, which I discuss in my video Does Diet Soda Increase Stroke Risk as Much as Regular Soda?.

At 1:14 in my video, you can see a chart of how much added sugar the American public is consuming. The data show that only about 1 percent meet the American Heart Association recommendation to keep added sugar intake down to 5 or 6 percent of daily caloric intake. Most people are up around 15 percent, which is where cardiovascular disease risk starts to take off. There is a doubling of risk at about 25 percent of calories and a quadrupling of risk for those getting one-third of their daily caloric intake from added sugar.

Two hundred years ago, we ate an estimated 7 pounds of sugar annually. Today, we may consume dozens of pounds of sugar a year. We’re hardwired to like sweet foods because we evolved surrounded by fruit, not Froot Loops, but this adaptation is “terribly misused and abused” today, “hijacked” by the food industry for our pleasure and their profits. “Why are we consuming so much sugar despite knowing too much can harm us?” Yes, it may have an addictive quality and there’s the hardwiring, but the processed food industry isn’t helping. Seventy five percent of packaged foods and beverages in the United States contain added sweeteners, mostly coming from sugar-sweetened beverages like soda, which are thought responsible for more than a 100,000 deaths worldwide and millions of years of healthy life lost. Given this, can we just switch to diet sodas? By choosing diet drinks, can’t we get that sweet taste we crave without any of the downsides? Unfortunately, studies indicate that “[r]outine consumption of diet soft drinks is linked to increases in the same risks that many seek to avoid by using artificial sweeteners—namely type 2 diabetes, metabolic syndrome heart disease, and stroke.” At 3:15 in my video, you can see data showing the increased risks of cardiovascular disease associated with regular soft drinks and also diet soda. They aren’t that dissimilar.

“In other words, the belief that artificially sweetened diet beverages reduce long-term health risks is not supported by scientific evidence, and instead, scientific data indicate that diet soft drink consumption may contribute to the very health risks people have been seeking to avoid.” But, why? It makes sense that drinking all that sugar in a regular soft drink might increase stroke risk, due to the extra inflammation and triglycerides, but why does a can of diet soda appear to increase stroke risk the same amount? It’s possible that the caramel coloring in brown sodas like colas plays a role, but another possibility is that “artificial sweeteners may increase the desire for sugar-sweetened, energy-dense beverages/foods.”

The problem with artificial sweeteners “is that a disconnect ultimately develops between the amount of sweetness the brain tastes and how much glucose [blood sugar] ends up coming to the brain.” The brain feels cheated and “figures you have to eat more and more and more sweetness in order to get any calories out of it.” So, “[a]s a consequence, at the end of the day, your brain says, ‘OK, at some point I need some glucose [blood sugar] here.’ And then you eat an entire cake, because nobody can hold out in the end.”

If people are given Sprite, Sprite Zero (a zero-calorie soda), or unsweetened, carbonated, lemon-lime water, but aren’t told which drink they’re getting or what the study is about, when they’re later offered a choice of M&M’s, spring water, or sugar-free gum, who do you think picks the M&M’s? Those who drank the artificially sweetened soda were nearly three times more likely to take the candy than those who consumed either the sugar-sweetened or unsweetened drinks. So, it wasn’t a matter of sweet versus non-sweet or calories versus no-calories. There’s something about non-caloric sweeteners that somehow tricks the brain.

The researchers did another study in which everyone was given Oreos and were then asked how satisfied the cookies made them feel. Once again, those who drank the artificially sweetened Sprite Zero reported feeling less satisfied than those who drank the regular Sprite or the sparkling water. “These results are consistent with recent [brain imaging] studies demonstrating that regular consumption of [artificial sweeteners] can alter the neural pathways responsible for the hedonic [or pleasure] response to food.”

Indeed, “[t]he only way really to prevent this problem—to break the addiction—is to go completely cold turkey and go off all sweeteners—artificial as well as fructose [table sugar and high fructose corn syrup]. Eventually, the brain resets itself and you don’t crave it as much.”

We’ve always assumed the “[c]onsumption of both sugar and artificial sweeteners may be changing our palates or taste preferences over time, increasing our desire for sweet foods. Unfortunately, the data on this [were] lacking”…until now. Twenty people agreed to cut out all added sugars and artificial sweeteners for two weeks. Afterwards, 95 percent “found that sweet foods and drinks tasted sweeter or too sweet” and “said moving forward they would use less or even no sugar.” What’s more, most stopped craving sugar within the first week—after only six days. This suggests a two-week sugar challenge, or even a one-week challenge, may “help to reset taste preferences and make consuming less or no sugar easier.” Perhaps we should be recommending it to our patients. “Eating fewer processed foods and choosing more real, whole, and plant-based foods make it easy to consume less sugar.”

Speaking of stroke, did you see my Chocolate and Stroke Risk video?

For more on added sugars, see:

You may also be interested in my videos on artificial and low-calorie sweeteners:

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:

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: