The important point of that post was that the previous (long-standing) evidence for possible beneficial effects of a small intake of alcohol on human mortality has recently been called into question. The previous evidence had been based on observing a so-called J-curve when plotting human mortality against alcohol intake, as shown in the first figure (below). Naturally, this graph might be right or wrong, and this distinction is the point at issue here.
Previous advice from WHO (ie. before last January) was based on comprehensive studies like this one (from which the above figure was taken): Di Castelnuovo A., Costanzo S., Bagnardi V., Donati M.B., Iacoviello L. and de Gaetano G. (2006) Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Archives of Internal Medicine 166: 2437-2445. This 17-year-old paper concluded:
Low levels of alcohol intake (1-2 drinks per day for women and 2-4 drinks per day for men) are inversely associated with total mortality in both men and women. Our findings, while confirming the hazards of excess drinking, indicate potential windows of alcohol intake that may confer a net beneficial effect of moderate drinking, at least in terms of survival.More recently, there are also summary papers like this one: Giovanni de Gaetano and Simona Costanzo (2017) Alcohol and health: praise of the J curves. Journal of the American College of Cardiology 70: 923–925. Clearly, this one supports the existence of the J-curves!
However, since then, this J-curve graph has been claimed to not be J-shaped after all, but to be monotonically increasing instead (ie. the more alcohol consumed then the greater the mortality), leading to the conclusion that the safest amount of alcohol is zero intake. That is, the J-curve was previously accepted as being correct, but it is now claimed to be wrong. This conclusion was clearly stated in a report by the Global Burden of Disease (GBD) collaborators; and the WHO has followed them.
My previous blog post called this new conclusion into question. I noted that, while this conclusion is literally true, it is not all of the truth — small amounts of alcohol were shown to be equally as safe as zero alcohol intake. I also claimed that I am appalled by this act of omission (leaving out part of the truth). I will continue my story here, pointing out some limitations of the study mentioned above, along with updated information from a more recent paper.
The GBD collaborators paper
The paper that I have been referring to above, by the Global Burden of Disease collaborators, is:Alcohol use and burden for 195 countries and territories, 1990—2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (2018) 392: 1015–1035.
Since I am questioning it, let’s look at what is in there. Their written summary in two sections of the paper is:
Methods
Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs [disability-adjusted life-years]. For our exposure estimates, we extracted 121,029 data points from 694 sources across all exposure indicators. For our relative risk estimates, we extracted 3,992 relative risk estimates across 592 studies. These relative risk estimates corresponded to a combined study population of 28 million individuals and 649,000 registered cases of respective outcomes.Findings
Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5—3.0) of age-standardised female deaths and 6.8% (5.8—8.0) of age-standardised male deaths, [so that] the attributable burden for men around three times higher than that for women in 2016. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0—0·8) standard drinks per week.There is no doubt that the contributors have performed an impressive study. They have collated a massive amount of data, and developed some innovative ways to analyze that data, accounting for previous limitations. However, there is still one basic limitation in this type of work — the authors compiled data from pre-existing sources, rather than doing an experiment of their own.
There are ways to grade what is called The Strength of Evidence of any published scientific paper. In this case, Lewis Perdue’s Stealth Syndromes Study grades this type of paper as only Strength C, with this comment:
Published pre-prints may be credible depending upon the study design (clinical, randomized, etc.), the investigators, methods, and institutional affiliations.Basically, there are these possible Complicating Factors For Human Studies:
C-SRD: Self reported / selected data
C-SRDb: Social pressure / desirability approval bias
So, we do not have Grade A evidence, or even Grade B evidence. There are thus serious limitations to the conclusions from the study, and we should bear that in mind when evaluating them. Basically, these are what we call “observational” studies, which do not yield causal data, but merely offer potential connections or indications between observations and conclusions.
Follow-up paper
The paper discussed above is from the Global Burden of Disease (GBD) Study 2016. There has been another part of this series of studies that has been published since then, this time by the GBD 2020 Alcohol Collaborators:Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020. Lancet (2022) 400: 185–235
Their notes about their new work are:
For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020.This study thus focuses on variation among ages and countries, which is valuable in-depth information. Their results are:
The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day.Note that they refer to the existence of J-curves for some age groups. So, J-curves do exist! Even using roughly the same data as in 2016! Furthermore, note that zero drinks is, indeed, the lower alcohol limit for safety, but that the authors also have a table updating the 2016 results to much less extreme levels. This table is shown as the second figure above.
This sort of apparent conflict among publications is the basic problem with what we call meta-analyses (where the results of multiple studies are considered together). It matters very much which studies are included in the meta-analysis, and what data analyses are done on the results (this is how you end up with Strength C evidence).
Very thorough analysis!
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