Some issues we eat or drink elevate our threat of lethal ailments like coronary heart illness or most cancers. However, unusually, a current paper argues that, as soon as now we have these ailments, a number of the similar components can present the other affiliation with survival in observational research. This survival twist – described within the paper as a threat–survival paradox and dubbed “Cuomo’s Paradox” – raises questions on how prevention findings translate to survivorship. It would not, by itself, overturn present dietary steerage.
Dietary epidemiology, the examine of how weight loss plan impacts illness threat and development, has been key in figuring out modifiable components for continual ailments. These embody components reminiscent of weight problems, hypertension, excessive ldl cholesterol, smoking, and alcohol consumption.
Typically, although, multiple piece of analysis will level to a paradox between a pre-diagnosis threat issue and its impact on post-diagnosis survival that challenges typical assumptions. In a brand new perspective paper, Raphael Cuomo, PhD, from the Division of Anesthesiology at UC San Diego’s Faculty of Medication, has examined this risk-survival paradox throughout 4 dietary components and two ailments: most cancers and coronary heart illness.
“Repeated findings confirmed that dietary exposures linked to illness threat had been related to higher survival as soon as illness was current,” mentioned Cuomo. “This paper formalizes the final precept, which the scientific neighborhood has named ‘Cuomo’s Paradox,’ that dietary components which assist stop most cancers or heart problems could be impartial and even present the other affiliation with survival after prognosis.”
Right here is Cuomo’s Paradox in easy phrases: A dietary issue can elevate an individual’s probabilities of getting a illness, however, in sure folks and with particular dietary selections, it may be related to longer survival. For the current examine, Cuomo targeted on the components of obesity, alcohol, cholesterol, and antioxidant dietary supplements in relation to post-diagnosis survival in sufferers with most cancers and heart problems.
“It must be famous that there exist some illness, reminiscent of diabetes and important hypertension, the place extant literature reveals little or no proof of risk-survival reversal, implying that the paradox might not be common,” Cuomo explains. “On this article, I limit our evaluation to most cancers and heart problems, given their prominence as international causes of demise and the in depth literature documenting paradoxical survival affiliation in these populations.”
Weight problems
Many research have proven that, earlier than a prognosis of illness, larger physique weight raises the chance of coronary heart issues and lots of cancers. After prognosis, nevertheless, some cohorts have reported higher brief‑time period survival amongst sufferers with larger BMI. Longer survival is likely to be because of having further vitality reserves, variations in tumor biology or therapy tolerance, or measurement points, reminiscent of BMI vs physique composition, so it should not be interpreted as proof of weight problems being helpful.
Alcohol
Even ingesting reasonable quantities of alcohol has been linked to an elevated most cancers threat. Nonetheless, for some cancers (like breast or colorectal) and in coronary heart illness, some observational research have reported longer survival amongst reasonable drinkers in contrast with abstainers, notably when excluding individuals who give up ingesting because of sickness (so-called “sick quitters”). Though this profit disappears or reverses for sure cancers, together with liver, head and neck cancers. It also needs to be identified that these findings are extremely delicate to confounding (e.g., “sick‑quitter” bias) and don’t justify beginning or persevering with alcohol for survival advantages.
Ldl cholesterol
Earlier than illness, excessive ranges of low-density lipoprotein (LDL or “dangerous” ldl cholesterol) are a significant driver of coronary heart illness. In superior coronary heart failure and late‑stage sickness, larger measured ldl cholesterol has generally tracked with higher survival, a sample doubtless influenced by sickness severity, irritation, and dietary standing moderately than a protecting impact of excessive LDL. This doesn’t argue towards LDL‑reducing for prevention.
Antioxidant dietary supplements
Antioxidants are supposed to assist cut back oxidative stress, an imbalance in reactive oxygen species (ROS) or free radicals and the physique’s capacity to neutralize them, which causes mobile harm that’s thought to contribute to most cancers. Nonetheless, giant randomized trials have proven that some antioxidant dietary supplements elevated most cancers threat in sure teams – in people who smoke, for instance, beta-carotene could act as a pro-oxidant, worsening moderately than stopping most cancers. These findings reveal that timing, dosage, and particular person biology matter, and that dietary supplements are usually not uniformly helpful and could be dangerous.
“It’s all the time essential to think about when different components is likely to be influencing the outcomes, however even when research account for issues like smoking, age, current well being issues and therapy, we nonetheless see patterns that line up with Cuomo’s Paradox,” the scientist mentioned.
Cuomo factors out two of the examine’s key limitations: “reverse causation” and “survivor bias.” Reverse causation is the traditional “chicken-and-egg” downside seen in observational research. Let’s say a examine finds that individuals with low physique weight die sooner after receiving a prognosis of coronary heart illness. At first look, which may appear like low physique weight causes early demise. However the reverse could also be true: people who find themselves already sicker could drop pounds as a result of illness or its therapy. Meaning the sickness is inflicting low physique weight, and the low weight is only a marker of being unwell, not the trigger of poor survival. Lots of Cuomo’s “paradoxes” could possibly be partly defined by reverse causation. The opposite rationalization, survival bias, refers to the truth that research miss the sickest sufferers as a result of they die early, and those that dwell lengthy sufficient to be studied could already be more healthy or biologically advantaged.
What Cuomo is suggesting – albeit cautiously at this stage, with out additional research to again it up – is that recommendation on tips on how to keep away from illness (that’s, prevention) won’t work the identical manner for survivors (that’s, tips on how to dwell longer with the illness). Present vitamin pointers usually assume that prevention and survival are aligned, however this analysis means that they are often very totally different.
“Wholesome must be outlined relative to an individual’s stage in life and objectives,” he mentioned. “Cuomo’s Paradox reframes well being as prevention versus survival. My analysis has uncovered pre-diagnosis versus post-diagnosis as a core variable in vitamin. It grew to become clear to me that prevention recommendation and survivorship recommendation have to be separated.”
Whereas there isn’t but a significant opinion piece from top-tier medical journals on Cuomo’s Paradox, there are a number of current expert-informed commentaries and essays that debate and reply to the idea. Care City Media, for instance, urges clinicians, particularly in oncology and cardiology, to rethink normal dietary recommendation. It advocates for stage-specific pointers, noting that methods geared toward stopping illness, reminiscent of weight reduction or ldl cholesterol reducing, would possibly undermine survival throughout sickness until these methods are tailored thoughtfully. Best Info Cloud suggests transferring from a one-size-fits-all strategy to vitamin to a personalised strategy.
Granted, not everybody will agree with Cuomo’s risk-survival paradox idea. Extra research, particularly randomized trials, are wanted earlier than making official adjustments to dietary suggestions for sufferers who have already got most cancers or coronary heart illness.
The examine was revealed in The Journal of Nutrition.
Supply: UC San Diego School of Medicine
