Exploring the Link Between Sugar and Disease

The research strongly suggests that it’s time to rethink our nutritional choices and urge patients to do likewise.

By Paul Cerrato, MA, senior research analyst and communications specialist and John Halamka, M.D., Diercks President, Mayo Clinic Platform

In an earlier column, we reviewed the evidence suggesting that dietary sugar increases the risk of cancer and may speed up its progression in patients who already have the disease. A deeper dive into the research suggests that dietary sugar and ultra processed foods contribute to a variety of degenerative diseases. 

A large French study that involved over 100,000 participants over the age of 18 found that overall cancer risk was 17% greater among persons consuming the most sugar, compared to those consuming the least. The risk of breast cancer was even more significant: 51% greater amongst those consuming the most sugar. Similarly, systematic reviews and meta-analyses of observational studies revealed a significant association between dietary sugar and “8 endocrine/metabolic outcomes, 10 cardiovascular outcomes, seven cancer outcomes, and 10 other outcomes (neuropsychiatric, dental, hepatic, osteal, and allergic).”

Of course, critics will point out that an association or correlation doesn’t prove causation. But there are several steps one can take to address this shortcoming. While randomized controlled trials remain the gold standard to determine what’s true and what’s not, they are expensive and can be unethical when the intervention under consideration is suspected of doing harm. An alternative is to consider using observational studies like case/control and cohort trials to justify a specific therapy or prove a lifestyle choice is harmful. And while such observational studies may still mislead because some confounding variables have been overlooked, there are epidemiological criteria that strengthen the weight given to these less than perfect studies. The following are part of a more inclusive set of guidelines referred to as the Bradford Hill Criteria:

• A stronger association or correlation between two variables is more suggestive of a cause/effect relationship than a weaker association.
• Temporality. The alleged effect must follow the suspected cause not the other way around. It would make no sense to suggest that exposure to Mycobacterium tuberculosis causes TB if all the cases of the infection occurred before patients were exposed to the bacterium.
• A dose-response relationship exists between alleged cause and effect. For example, if researchers find that a blood lead level of 10 mcg/dl is associated with mild learning disabilities in children, 15 mcg/dl is linked to moderate deficit, and 20 mcg/dl with severe deficits, this gradient strengthens the argument for causality.
• A biologically plausible mechanism of action linking cause and effect strengthens the argument. In the case of lead poisoning, there is evidence pointing to neurological damage brought on by oxidative stress and a variety of other biochemical mechanisms.
• Repeatability of the study findings: If the results of one group of investigators are duplicated by independent investigators, that lends further support to the cause/effect relationship.

Investigators have found a dose response relationship between dietary sugar and several diseases, including stroke, depression, and cancer. A meta-analysis that included 32 studies found higher intake of sugar-sweetened beverages (SSBs) increase the relative risk (RR) of stroke by 12%, depression by 25%, and cancer by 10%. Wang et al explain: “The associations were dose-dependent, with per 250 mL increment of SSB intake daily increasing the risk of stroke, depression, cancer, and all-cause mortality by RR 1.09 … 1.08…  1.17… and 1.07, respectively.” Similarly, the meta-analysis has shown that the research is repeatable. Researchers have also established a plausible mechanism of action that explains the relationship between sugar and disease by contributing to inflammation, oxidative stress, obesity, and metabolic dysfunction.

Dietary sugar is part of a larger group referred to as ultra-processed foods (UPFs). They typically include packaged products that contain high fructose corn syrup, hydrogenated oils, sugar-sweetened beverages, breads and cereals made from white flour or white rice, and processed meats. The American Heart Association considers the harm caused by UPFs so significant that it recently published a scientific advisory statement about the problem, concluding that “diets high in these products consistently have been linked with heightened risks of cardiometabolic diseases and mortality. Most ultra-processed foods are calorie dense and high in saturated fat, added sugars, and sodium. But beyond nutritional quality, there’s mounting evidence that the processing these products undergo and the additives they contain may contribute to the harms in a variety of ways.”

Similarly, a recent issue of Nature Medicine featured ultraprocessed diet on its cover, and published a randomized clinical trial that compared minimally processed food (MPF) to UPFs to see how they affected volunteers’ weight. Since it was a carefully controlled intervention study, it too addressed the criticism that all the evidence linking sugar to disease was weak because the research has been mostly observational.  Volunteers in the new study who consumed the MPF regime lost about twice the weight as those on the UPF diet, which links UPF with obesity, which in turn has been shown to be a risk factor for a long list of diseases.

There is even reason to suspect that dietary sugar may contribute to neurodegenerative diseases. Cheng et al  reviewed dietary records of over 12,000 participants in the National Health and Nutrition Examination Survey and found those consuming 25% of more of their calories from added sugar were more than 3 times as likely to have Parkinson’s Disease, when compared to those in the lowest quartile. Their analysis took into account several possible confounding factors that may have distorted the findings. Admittedly, there are no randomized controlled trials available to establish a cause/effect relationship. However, consistent with studies on other chronic diseases, an independent analysis found that “foods associated with the reduced rate of PD progression included fresh vegetables, fresh fruit, nuts and seeds, nonfried fish, olive oil, wine, coconut oil, fresh herbs, and spices (P < 0 05). Foods associated with more rapid PD progression include canned fruits and vegetables, diet and nondiet soda, fried foods, beef, ice cream, yogurt, and cheese.”

Considering all the evidence connecting poor diet to a variety of life-threatening diseases, it’s time to rethink our nutritional choices and tactfully encourage patients to do the same.