Got it. I’ll look into the long-term health consequences of drinking one liter of diet Pepsi daily over 30–40 years in an otherwise healthy, active 50-year-old man. I’ll focus on high-quality, peer-reviewed scientific and medical research that examines the impact of chronic consumption of diet sodas—especially those sweetened with artificial sweeteners like aspartame—on outcomes such as cardiovascular disease, cancer, metabolic health, neurological function, and overall mortality.I’ll update you as soon as I have a clear summary of the evidence.

Long-Term Health Effects of Daily Diet Pepsi Consumption

Introduction: Regularly consuming one liter of Diet Pepsi (or any diet soda) per day means chronic exposure to artificial sweeteners (primarily aspartame, plus others like acesulfame-K) and other soda ingredients. Research over decades has examined whether such intake is truly “health-neutral” or if it carries long-term risks. The individual in question is a 50-year-old healthy, active man; this context is important because lifestyle and health status can influence outcomes. Many findings on diet soda come from observational studies, which have noted that heavy diet soda consumers often have other risk factors (e.g. higher BMI, more smoking, poorer diet)www.sciencemediacentre.org. Researchers adjust for these factors, but some residual confounding may remain. Below, we summarize high-quality evidence on various health domains – cardiovascular disease, metabolic health, cancer, cognitive/neurological effects, kidney function, and overall mortality – focusing on systematic reviews and large cohort studies in top-tier journals.

Cardiovascular Health

Several large studies suggest that long-term daily consumption of diet soda is associated with elevated cardiovascular risk. In a 2022 BMJ study of 103,000+ adults (mostly women) followed ~9 years, those with higher artificial sweetener intake had a higher incidence of overall cardiovascular disease (CVD) eventspubmed.ncbi.nlm.nih.gov. Specifically, aspartame, acesulfame-K, and sucralose intake showed a potential direct association with increased risk of heart disease and strokepubmed.ncbi.nlm.nih.gov. Similarly, an analysis from the French NutriNet-Santé cohort found that participants consuming the most artificial sweeteners had higher rates of coronary heart disease, and certain sweeteners were linked to cerebrovascular disease (stroke) riskpmc.ncbi.nlm.nih.gov. These observational links were modest in magnitude but persisted even after controlling for diet and lifestyle.Meta-analyses reinforce these findings. A 2024 systematic review pooled 12 prospective cohorts (~1.2 million people) and reported that drinking at least one diet beverage daily was associated with increased CVD eventspubmed.ncbi.nlm.nih.gov. Notably, high diet soda intake was linked to greater risk of stroke (pooled hazard ratio ~1.15) and cardiovascular mortality (HR ~1.29) over timepubmed.ncbi.nlm.nih.gov. Some studies (including the U.S. Nurses’ Health Study) have not found statistically significant CVD risk from diet drinks, indicating mixed evidencepmc.ncbi.nlm.nih.gov. However, the overall trend in recent research is that diet soda provides no cardiovascular benefit and may even contribute to riskwww.sciencemediacentre.org. Mechanistically, artificial sweeteners might impact gut microbiota, vascular function, or appetite in ways that influence CVD risk factors, though causation is unproven. Given our patient’s profile (male, age 50, active), it’s worth noting much of the cohort data skew female; still, no evidence suggests men are exempt from these associationswww.sciencemediacentre.org. In summary, daily diet soda intake has been linked to higher rates of heart attacks, strokes, and related mortality, especially at high consumption levels, even if the absolute risk for a healthy individual might be lower than for someone with other risk factors.

Metabolic Effects (Metabolic Syndrome & Diabetes)

One liter of diet cola contains no sugar or calories, yet paradoxically, epidemiologic studies have found associations between diet soda and metabolic disorders. Multiple large cohorts (e.g. Framingham, ARIC, MESA) reported that people who drink diet soda regularly have higher odds of developing metabolic syndrome and type 2 diabetes over timepmc.ncbi.nlm.nih.gov. For instance, a recent analysis from the NutriNet-Santé cohort (105,000+ individuals) found that high consumers of aspartame, sucralose, and acesulfame-K had a significantly elevated risk of type 2 diabetes compared to non-consumerspmc.ncbi.nlm.nih.gov. Even after excluding early cases (to reduce reverse causation, i.e. people who switched to diet soda because they were already at risk), the association with diabetes remained robustwww.nature.com. The magnitude of risk increase in such studies is on the order of ~20–30% higher relative risk for the highest intake group, though again causality is debated.Importantly, these findings contributed to a 2022 World Health Organization (WHO) systematic review on non-sugar sweeteners. That review (covering both randomized trials and cohort studies) concluded there is no clear long-term benefit of artificial sweeteners for weight control, and it found low-certainty evidence that higher nonnutritive sweetener use might be linked to increased weight/BMI, higher type 2 diabetes incidence, and even cardiovascular eventspmc.ncbi.nlm.nih.gov. In May 2023, WHO officially recommended against using artificial sweeteners for weight management, since substituting sugar with diet sweeteners didn’t consistently improve body fat in the long run and potential undesirable effects (like diabetes risk) were observedpmc.ncbi.nlm.nih.gov.From a mechanistic perspective, several hypotheses exist: chronic artificial sweetener use may alter gut microbiota and glucose metabolism, potentially impairing insulin sensitivity or promoting fat storage. Some studies have also noted that diet soda drinkers may unconsciously compensate by eating more calories, mitigating any calorie-saving benefit. That said, clinical trials show mixed results – short-term trials sometimes find that replacing sugary drinks with diet drinks can modestly improve weight and glucose control (since you’re cutting lots of sugar calories)pmc.ncbi.nlm.nih.gov. But no RCT has followed people for decades. Overall, for an otherwise healthy, active 50-year-old man, one liter of diet soda daily could contribute to metabolic changes that elevate the risk of weight gain, insulin resistance, and eventually type 2 diabetes. These risks are not as immediate or large as those from drinking a liter of regular sugary soda, but they are not negligible. Vigilance about diet quality and total calorie intake is needed if one consumes diet soda, as it’s not a guaranteed “free pass” metabolically.

Cancer Risk

The question of artificial sweeteners and cancer has been studied for over 40 years, especially regarding aspartame (Diet Pepsi’s primary sweetener). Regulatory agencies (FDA, EFSA) have long deemed aspartame safe at typical intakes, based on animal and human data showing no clear carcinogenic effectwww.cancer.gov. However, recent research has kept the debate alive. In July 2023, the International Agency for Research on Cancer (IARC) – a WHO cancer research arm – classified aspartame as “possibly carcinogenic to humans” (Group 2B)www.cancer.gov. This 2B category is used for agents with limited evidence of causing cancer in humans and less-than-sufficient evidence in animals. In aspartame’s case, IARC noted a possible link to hepatocellular carcinoma (liver cancer) in a few observational studies, but the evidence was not definitive (chance or bias couldn’t be ruled out)www.cancer.gov www.cancer.gov. Notably, no public health agencies have suggested people avoid aspartame entirely – at the same time IARC made its hazard classification, the Joint WHO/FAO Expert Committee on Food Additives (JECFA) reaffirmed the acceptable daily intake for aspartame, concluding that it has not been proven to cause harm at doses up to 40 mg/kg body weight (far above a liter of diet soda per day)www.cancer.gov.What do large epidemiologic studies show? Overall, human studies have not found consistent evidence that diet soda or artificial sweeteners cause cancer. An umbrella review of dozens of studies found only weak, inconsistent associations between consuming artificially sweetened beverages and overall cancer incidence or mortalitywww.cancer.gov. For example, one U.S. cohort of older women found a higher risk of kidney cancer in heavy diet soda drinkers, but a European cohort did notwww.cancer.gov. A French cohort study (NutriNet-Santé) reported that people with the highest artificial sweetener intakes had a slightly elevated risk of cancer (all types combined) compared to non-consumerswww.cancer.gov. The excess risk was small, and specific cancers varied; when they looked specifically at obesity-related cancers, the risk was a bit higher in the sweetener groupwww.cancer.gov. Conversely, an Australian long-term study found no association between diet beverage intake and obesity-related cancerswww.cancer.gov.For specific cancers, such as brain tumors, leukemias, or others that caused past controversies: extensive research in the 1990s–2000s (including the NIH-AARP diet study of ~500k people) found no clear link between aspartame and risks of those cancerswww.cancer.gov www.cancer.gov. The slight signals that led to the IARC classification – primarily regarding liver cancer – came from at most three studies with methodological limitationswww.cancer.gov. In summary, current high-quality evidence does not demonstrate that daily diet soda causes cancer in humans. There may be a slight increase in risk of certain cancers (e.g. perhaps liver or breast cancer) in high consumers, but results are inconsistent and confounded. The absolute cancer risk for an individual healthy 50-year-old man drinking diet soda is likely very low. Nonetheless, given the recent IARC flag and the lingering uncertainties, continuing to monitor new research is prudent.

Cognitive and Neurological Effects

Beyond the cardiovascular and metabolic impacts, researchers have explored whether long-term diet soda intake affects the brain – notably risk of stroke, dementia, or cognitive decline. A pivotal study in 2017 (Framingham Heart Study Offspring cohort) grabbed headlines by reporting that people who drank one or more diet sodas per day had a significantly higher risk of stroke and dementia over a 10-year follow-upwww.heart.org. In that analysis, diet soda consumers were almost 3× more likely to develop an ischemic stroke or Alzheimer-type dementia than those who drank nonewww.heart.org. Interestingly, the study did not find these risks with regular sugar-sweetened soda – only the artificially sweetened beverages showed the associationwww.heart.org. This suggests it wasn’t just overall unhealthy behavior causing the outcome, though the authors cautioned that this does not prove causation (it was “hypothesis-generating”www.heart.org). Experts noted that people with vascular risk factors might switch to diet drinks (reverse causation), and indeed diet soda users in that cohort tended to have more hypertension and diabetes at baselinepmc.ncbi.nlm.nih.gov.Since then, additional studies have observed similar patterns. For example, an analysis combining the Nurses’ Health Study and Health Professionals Follow-up Study found that high intake of low-calorie sweetened drinks was associated with a greater risk of hemorrhagic stroke (in the brain) in those cohortspmc.ncbi.nlm.nih.gov. However, not all data are consistent – some longitudinal studies have not found a significant link between diet beverages and cognitive decline or Alzheimer’s disease when controlling for other factorspmc.ncbi.nlm.nih.gov. There is also emerging research on whether artificial sweeteners could impact the brain’s reward centers or memory over time, but no firm conclusions yet.For our 50-year-old man, these findings raise a caution flag that habitual diet soda intake might contribute to brain aging or neurovascular risk in the long run. Stroke is a major concern with aging; if diet soda even slightly increases stroke risk, that becomes more relevant in one’s 70s and 80s. Dementia is multifactorial, and while diet soda alone is unlikely a major driver, the observed association means it’s something to watch (especially if other risk factors for dementia are present). In short, some evidence suggests chronic diet soda consumption could negatively affect brain health, particularly vascular aspects (strokes) and perhaps cognitive decline, though more research is needed to confirm direct effects. Maintaining overall cardiovascular health (through exercise, diet, blood pressure control) is likely the best protection, and that will also help mitigate any small risk from diet beverages.

Kidney Function

Long-term diet soda intake may have consequences for the kidneys. Notably, the high consumption of cola (even diet cola) introduces phosphoric acid and artificial additives that might impact kidney health. In the authoritative Nurses’ Health Study, researchers followed over 3,000 women for 20 years and examined change in kidney function. Women who drank ≥2 servings of diet soda per day had a two-fold increased odds of significant kidney function decline (≥30% drop in estimated GFR) compared to those who drank <2 per daypubmed.ncbi.nlm.nih.gov. In fact, by the end of the study, the high diet soda group had about a 30% greater reduction in kidney function over two decades than non-drinkerswww.kidney.org. Interestingly, this association was not seen with sugar-sweetened soda – only diet soda correlated with faster declinewww.npr.org. No link was found with increased albuminuria, suggesting the effect was more on filtration capacity than on early kidney damage markerspubmed.ncbi.nlm.nih.gov.Why might diet soda harm the kidneys? One hypothesis is that artificial sweeteners and the cola’s acidity may induce subtle chronic injury. Another factor is that diet cola often contains phosphorus (as phosphoric acid), which in high amounts can strain the kidneys and promote kidney stones or renal calcium deposition. Additionally, heavy diet soda consumption might be a marker for other behaviors (like high sodium intake, which also appeared deleterious to kidneys in the NHS study)www.npr.org. In our scenario, the man is physically active and presumably health-conscious, so he might not have the typical risk profile of the soda-drinking women in the study (who were slightly older and mostly white females). Nonetheless, the physiology of kidney aging is similar, and a chronic acid load from multiple colas a day could accelerate age-related GFR decline. While one liter is not extreme (some people drink 2L+ daily), it still exceeds the “≥2 servings” threshold (~2 cans). Over 30–40 years, this could plausibly translate to a noticeable impact on renal function by his 80s. Keeping hydrated with water and moderating cola intake could help preserve kidney health.

Mortality and Overall Health

The ultimate question for many is whether daily diet soda affects longevity or risk of premature death. Several high-quality cohort studies have evaluated all-cause mortality in relation to artificially sweetened beverages. The consensus of recent evidence is that heavy diet soda consumption is associated with a modest increase in mortality risk. For example, an updated 2023 meta-analysis of 11 prospective studies (over 2.1 million total participants) found that the highest category of diet beverage intake was linked to about a 13% higher risk of all-cause death compared to the lowest intake categorypubmed.ncbi.nlm.nih.gov. The same analysis found a similar elevated risk for cardiovascular mortality in diet drink consumerspubmed.ncbi.nlm.nih.gov. Importantly, these risks were lower than those associated with regular sugar-sweetened beverages – i.e. drinking a liter of regular Pepsi daily would pose a greater mortality hazard – but the diet drinks were not completely benignpubmed.ncbi.nlm.nih.gov.Individual large studies echo this. A 2019 JAMA Network study of 450,000 Europeans (EPIC cohort) reported that participants who drank ≥2 glasses of artificially sweetened drinks daily had a higher all-cause death rate than those who drank none, even after controlling for lifestyle. Similarly, the Women’s Health Initiative cohort linked diet soda intake to increased mortality, especially from cardiovascular causes. Some of these associations might reflect underlying conditions (e.g. overweight individuals opting for diet soda), but the researchers do attempt to adjust for BMI, diet quality, etc. The WHO meta-analysis mentioned earlier also noted a signal for increased mortality with high non-sugar sweetener usepmc.ncbi.nlm.nih.gov. All told, the mortality impact seems to be on the order of a 10–15% relative increase in risk for heavy consumers. In practical terms, for a healthy 50-year-old man, this would slightly raise the probability of dying from any cause in the next decades – a subtle effect, but one that could matter when compounded over millions of people.It’s worth emphasizing that correlation is not causation. If someone is otherwise very healthy (good diet, exercises, normal weight, nonsmoker), that healthy lifestyle may counterbalance a lot of the risk associated with diet soda in the population data. Indeed, many high-quality studies try to isolate the effect of the soda itself, but residual confounders could still play a role. Nonetheless, the preponderance of evidence points to little if any health benefit from long-term diet soda use, and at least the possibility of harm in multiple domains.

Conclusion:

In summary, drinking one liter of diet Pepsi daily for decades may have several long-term health implications:

Cardiovascular: Long-term daily diet soda intake is associated with higher risks of heart disease and strokepubmed.ncbi.nlm.nih.gov. While not proof of causation, the lack of any cardiovascular benefit means it could be an unnecessary risk factor.
Metabolic: Chronic intake of aspartame and other sweeteners has been linked to weight gain, metabolic syndrome, and type 2 diabetes in observational studiespmc.ncbi.nlm.nih.gov. Short-term clinical trials don’t show major harms, but they also don’t show the hoped-for benefits in preventing obesity. A healthy, active individual might experience less metabolic impact than an overweight sedentary person, but the risk of diabetes appears elevated with daily use over many years.
Cancer: Current evidence does not conclusively tie diet soda to cancers. Regulatory bodies continue to deem aspartame safe within limits. A possible link to certain cancers (like liver cancer) has been observed but remains weak and inconsistentwww.cancer.gov www.cancer.gov. Overall cancer risk from one liter daily is likely very low, though prudence is warranted given recent questions.
Neurological: Some data indicate higher rates of stroke and dementia among older adults who consume diet drinks dailywww.heart.org. While causality is unproved, it suggests potential impacts on brain health over the long term.
Renal: High intake of diet soda (particularly colas) has been associated with kidney function decline in long-term studiespubmed.ncbi.nlm.nih.gov. Regularly consuming a liter a day could contribute to faster reduction in kidney filtration as one ages, compared to drinking water or other beverages.
Mortality: Large-scale evidence suggests a modest increase in all-cause mortality among habitual diet soda drinkerspubmed.ncbi.nlm.nih.gov. In other words, people who drink a lot of diet soda tend to live slightly shorter on average, although this could be partly due to other health factors. Bottom Line: For a healthy 50-year-old man, an occasional diet soda is not going to cause measurable harm. But making it a daily 1-liter habit for 30–40 years is associated with several potential long-term risks according to the best available evidence. These include a higher likelihood of cardiometabolic diseases (like strokes, heart attacks, and diabetes), possible contributions to cognitive decline or dementia, and strain on the kidneys. The man’s active lifestyle and good health certainly work in his favor and may mitigate some risks, but they do not render him immune to the physiological effects observed. Given that diet soda provides no nutritional benefit, many experts suggest moderation. Substituting some of that daily liter with water, tea, or other unsweetened beverages would be a prudent step to minimize any potential harm while still allowing the enjoyment of an occasional diet cola.Sources:
Debras et al., BMJ (2022) – NutriNet-Santé cohort study linking artificial sweetener intake with higher CVD riskpubmed.ncbi.nlm.nih.gov.
NutriNet-Santé (2023) – Prospective analysis showing aspartame, acesulfame-K, sucralose intake associated with increased type 2 diabetes incidencepmc.ncbi.nlm.nih.gov.
World Health Organization (2022/2023) – Systematic review and guideline advising against non-sugar sweeteners for weight control due to potential risk of diabetes, CVD, and no long-term weight benefitpmc.ncbi.nlm.nih.gov.
National Cancer Institute – Summary of studies on artificial sweeteners and cancer (no consistent evidence of harm; IARC classification of aspartame as 2B possible carcinogen based on limited data)www.cancer.gov www.cancer.gov.
Pase et al., Stroke (2017) – Framingham study reporting higher stroke and dementia risk with daily diet soda consumptionwww.heart.org.
Lin et al., Clin J Am Soc Nephrol (2011) – Nurses’ Health Study finding double the risk of kidney function decline in women drinking ≥2 diet sodas/daypubmed.ncbi.nlm.nih.gov.
Chen et al., Nutrition Journal (2024) – Meta-analysis of 11 cohorts indicating higher all-cause and CVD mortality with greater artificially sweetened beverage intakepubmed.ncbi.nlm.nih.gov.