by Marion Nestle

Currently browsing posts about: Research

Sep 7 2021

Nutrition research basics: Association does not equal causation

I subscribe to a newsletter, Obesity and Energetics Offerings, that often includes a section on “Headline versus Study.”  This demonstrates how  headline writers jump actual findings and draw attention-getting conclusions that the studies don’t always support.

Here are four examples, all from the UK Biobank study, an enormous epidemiologic investigation of half a million participants who filled out a dietary questionnaire, and then were followed and tested to see what diseases they developed.  These data enable investigators to link specific dietary factors to disease risk.

Such links are associations. 

This kind of study is not designed to determine whether a dietary factor causes (or prevents) a disease.  For that, other kinds of research are required.

These four examples examine associations of coffee intake with disease risk.  That’s all they do.

The headlines, however, assume causation—an epidemiologic fallacy.

I.  Headline: A Daily Dose of Coffee May Protect You from COVID-19.

Study: Self-Reported Dietary Behaviors and Incident COVID-19 in the UK Biobank.

Results: After multivariable adjustment, the odds (95% CI) of COVID-19 positivity was 0.90 (0.83, 0.96) when consuming 2–3 cups of coffee/day (vs. <1 cup/day), 0.88 (0.80, 0.98) when consuming vegetables in the third quartile of servings/day (vs. lowest quartile), 1.14 (1.01, 1.29) when consuming fourth quartile servings of processed meats (vs. lowest quartile), and 0.91 (0.85, 0.98) when having been breastfed (vs. not breastfed). Associations were attenuated when further adjusted for COVID-19 exposure, but patterns of associations remained.

Conclusions: In the UK Biobank, consumption of coffee, vegetables, and being breastfed as a baby were favorably associated with incident COVID-19; intake of processed meat was adversely associated.

Caveats:  This study looked at associations of several dietary factors to Covid risk: breastfed as baby, and consumption of coffee, tea, oily fish, processed meat, red meat, fruit, and vegetables.  Based on the results, the fallacious headlines could just as easily have read:

  • Vegetables may protect you from COVID-19
  • Being breastfed may protect you from COVID-19
  • Processed meats may increase your risk of COVID-19

The operative word is “may.”  This means that “may not” might also be appropriate.

2.  Headline: Too Much Coffee Can Cause Your Brain to Shrink, Raise Risk of Dementia by 53 Percent, Study Finds.

Study: Associations Among High Coffee Consumption, Brain Volume and Risk of Dementia and Stroke in UK Biobank.

Results: There were inverse linear associations between habitual coffee consumption and total brain (fully adjusted β per cup −1.42, 95% CI −1.89, −0.94), grey matter (β −0.91, 95% CI −1.20, −0.62), white matter (β −0.51, 95% CI −0.83, −0.19) and hippocampal volumes (β −0.01, 95% CI −0.02, −0.003), but no evidence to support an association with white matter hyperintensity (WMH) volume (β −0.01, 95% CI −0.07, 0.05). The association between coffee consumption and dementia was non-linear (Pnon-linearity= 0.0001), with evidence for higher odds for non-coffee and decaffeinated coffee drinkers and those drinking >6 cups/day, compared to light coffee drinkers. After full covariate adjustment, consumption of >6 cups/day was associated with 53% higher odds of dementia compared to consumption of 1–2 cups/day (fully adjusted OR 1.53, 95% CI 1.28, 1.83), with less evidence for an association with stroke (OR 1.17, 95% CI 1.00, 1.37, p = 0.055).

Conclusion: High coffee consumption was associated with smaller total brain volumes and increased odds of dementia.

Caveat: But why non-linear?  If coffee had these effects, shouldn’t more of it should have more of an effect?  Association, alas, does not equal causation.

3.  Headline: Your Morning Cup of Coffee May Lower Your Risk of Liver Disease.

Study: All Coffee Types are Associated with Lower Risk of Adverse Clinical Outcomes in Chronic Liver Disease: A UK Biobank Study.

Results: Compared to non-coffee drinkers, coffee drinkers had lower adjusted HRs of CLD (HR 0.79, 95% CI 0.72–0.86), CLD or steatosis (HR 0.80, 95% CI 0.75–0.86), death from CLD (HR 0.51, 95% CI 0.39–0.67) and HCC (HR 0.80, 95% CI 0.54–1.19). The associations for decaffeinated, instant and ground coffee individually were similar to all types combined.

Conclusion: The finding that all types of coffee are protective against CLD is significant given the increasing incidence of CLD worldwide and the potential of coffee as an intervention to prevent CLD onset or progression.

4.  Headline: Coffee Drinking Won’t Harm Your Health, New Study Reveals Caffeine Lowers Arrhythmia Risk.

Study: Coffee Consumption and Incident Tachyarrhythmias with Mendelian Randomization for Caffeine Metabolism in the UK Biobank.

Findings  In this large, prospective, population-based community cohort study of more than 300 000 participants, each additional daily cup of coffee was associated with a 3% reduced risk of developing an arrhythmia; these associations were not significantly modified by genetic variants that affect caffeine metabolism.

Meaning  Neither habitual coffee consumption nor genetically mediated differences in caffeine metabolism was associated with a heightened risk of cardiac arrhythmias.

Comment: Whether coffee drinking is good, bad, or indifferent to health has long been hotly debated.  For a long time, studies seemed aimed at proving coffee bad for health.  Now, studies seem aimed at showing the opposite.  The UK Biobank is expensive; its funders are largely private foundations and government agencies.  As far as I can tell, the coffee industry is not involved.  My take on all of this?  Take these epidemiological associations with a pinch of caffeine, and enjoy coffee if you like it.

Apr 14 2021

Study: how wines taste depends on what you think they cost

Thanks to Habib Benzian for telling me about this study.

Price information influences the subjective experience of wine: A framed field experiment.  Christoph Patrick Werner, et al.  Food Quality and Preference; 2021;92:104223

Highlights

  • First study manipulating wine prices using a framed field experiment.
  • Blind intensity ratings differ for 3 wines of different price and expert rating.
  • Blind pleasantness ratings do not differ for the same three wines.
  • Pleasantness of the budget wine increased when presented with a fake higher price.

The study: The authors got 140 people to taste wines of three different price ranges with open, deceptive, or no price information, and rate them for taste.

The main result: When price information was accurate, participants’ ratings were parallel to cost.  When price information was missing or deceptive, pleasantness ratings did not differ.

Wine A is inexpensive; Wine B is more expensive and rated as medium quality; wine C is expensive and rated outstanding

Authors conclusions: .”Thus, pricing information differentially influences the consumer’s subjective experience of wine, with no effects on intensity of taste ratings and no effects on pleasantness ratings with correct or no price information, but increased pleasantness of low-price wine when provided with a deceptive higher price. Thus, in wine may lay the truth, but its subjective experience may also lie in the price.”

Apr 2 2021

Weekend reading: More public funding for agricultural research

The press release says it all:  “New Report Highlights How Stagnant U.S. Public Funding for Agricultural Research Threatens Food Systems.”

Stagnant public funding for agricultural research is threatening the future vitality of U.S. food systems – posing risks to farmer productivity and profitability, the steady supply of affordable food for consumers, and ultimately global food security, according to a new report.

The report, jointly commissioned by Farm Journal Foundation and the American Farm Bureau Federation and authored by the IHS Markit Agribusiness Consulting Group, highlights the vital importance of public funding for agricultural research and development (R&D).

New innovations are crucial so that farmers can increase their productivity and meet rising global demand for food, even as climate change intensifies. The world population is expected to reach 10 billion by 2050, and food production will need to increase by 60%-70% to meet rising demand. While private-sector funding for agricultural R&D has been increasing, U.S. public spending has been flat for the past decade.

Here’s the big picture.

Here’s what’s happening with USDA research funding—flat.

And here’s what’s happening with overall agricultural research.  Public funding is flat.  Industry funding is rising rapidly. 

Why is this a problem?  Because industry funds research aimed at developing and marketing profit-making products

This leaves research aimed at public health to be supported by the public.  Research is needed to

  • Increase productivity
  • Improve crop protection
  • Promote animal health and welfare
  • Prevent animal diseases
  • Protect against pandemics
  • Reduce effects of climate change

Industry won’t fund these research areas if there’s no profit in them.

That’s why more public funds need to go to agricultural research.

Here’s a one page summary.

Here’s the full report.

 

 

 

Mar 23 2021

Vitamin C and the common cold. Again? Really?

I cannot believe that we are still talking about whether vitamin C prevents colds.  No such luck.

What triggered this is a recent and quite detailed critique of a 2018 meta-analysis of studies of this question: “Extra Dose of Vitamin C Based on a Daily Supplementation Shortens the Common Cold: A Meta-Analysis of 9 Randomized Controlled Trials.”

Its conclusion:  “The combination of supplemental and therapeutic doses of vitamin C is capable of relieving chest pain, fever, and chills, as well as shortening the time of confinement indoors and mean duration.”

You can read the detailed critique of this study for yourself, but I thought this was settled years ago by one of my all-time favorite nutrition studies: Karlowski TR, Chalmers TC, Frenkel LD, Kapikian AZ, Lewis TL, Lynch JM. Ascorbic acid for the common cold. A prophylactic and therapeutic trialJAMA 1975; 231: 1038–1042.

This fabulous study was done at NIH using NIH employees.  As the abstract puts it,

Three hundred eleven employees of the National Institutes of Health volunteered to take 1 gm of ascorbic acid or lactose placebo in capsules three times a day for nine months. At the onset of a cold, the volunteers were given an additional 3 gm daily of either a placebo or ascorbic acid.

The initial analysis of the data showed a highly significant effect of vitamin C in preventing colds or reducing symptoms.  But the trial had one major flaw: it had an usually big dropout rate.

One hundred ninety volunteers completed the study. Dropouts were defined as those who missed at least one month of drug ingestion. They represented 44% of the placebo group and 34% of those taking ascorbic acid.

These were good investigators.  They asked the dropouts why they had dropped out.  The reason: the study subjects knew (well, they thought they knew) whether they were taking vitamin C or the placebo.

The investigators reanalyzed the data according to what the study subjects thought they were taking.  Those who thought they were taking vitamin C had fewer colds and reduced symptoms—regardless of whether they were taking vitamin C or the placebo.  And those who thought they were taking the placebo had more colds and worse symptoms regardless of whether they really were taking the placebo or were actually taking vitamin C.

The authors’ cautious conclusion:

Analysis of these data showed that ascorbic acid had at best only a minor influence on the duration and severity of colds, and that the effects demonstrated might be explained equally well by a break in the double blind.

My conclusion: Vitamin C is one terrific placebo.

Nothing wrong with that, but that’s why I can’t believe investigators are still arguing about it.

Jan 13 2021

What’s happening with nutrition research?

I post often about conflicts of interest in nutrition research, mainly because I worry about how to  improve the quality of nutrition research studies.  Nutrition research is under attack for weaknesses well known to nutrition researchers, but recently rediscovered by critics outside the field who do not, unfortunately, propose meaningful alternatives (see this, for example).

Mainstream nutrition researchers have called for a new approach to nutrition research.

“The time has come for a national ‘moonshot’ on nutrition research,” said Dariush Mozaffarian, MD, DrPH, Dean of the Friedman School of Nutrition Science and Policy at Tufts University, chair of the session. “A strengthening of federal nutrition research has significant potential to generate new discoveries to improve and sustain the health of all Americans, reduce healthcare costs, improve health disparities, create new businesses and jobs, reinvigorate farms and rural communities, strengthen military readiness and optimize use of our natural resources.”

These researchers called for two priorities: a new authority for robust cross-governmental coordination of nutrition research; and strengthened authority and investment for nutrition research within the NIH.

It looks like they got it!  The NIH has proposed to transfer its existing Office of Nutrition Research into the NIH Director’s Office.

The National Institutes of Health (NIH) has proposed to transfer the Office of Nutrition Research (ONR) from the National Institute of Diabetes and Digestive and Kidney Diseases to the Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) within the NIH Office of the Director. DPCPSI was created by Congress to enhance NIH-wide coordination of cross-cutting research topics.

This proposed move follows two reports from NIH about nutrition research:

And now NIH says it is doing this!

The response from the public and the nutrition research community was overwhelmingly supportive. Such a move was also supported by the Council of Councils, an NIH advisory group, during a special meeting on December 30, 2020.

I’m pleased to share that this week, NIH has begun the official transfer of ONR to DPCPSI. This reorganization positions ONR to enhance engagement of the NIH Institutes and Centers in implementing the 2020-2030 Strategic Plan for NIH Nutrition Research to develop new collaborations and relationships focused on nutrition research within and outside NIH, and to ensure coordination of and leadership for nutrition research across the agency.

Will this strengthen the quality of nutrition research?  I certainly hope so.

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Apr 17 2020

Weekend reading: research on coronavirus and food

Research on this virus (officially SARS CoV-2, commonly COVID-19) is pouring out and filling every medical journal I typically read.  Here are a few recent articles on food-related aspects (some of these are not yet in print).

Obesity and its Implications for COVID-19 Mortality: The authors argue that the increased prevalence of obesity in Italy older adults as compared to its prevalence in China may account for the higher mortality observed in Italy.

Obesity is associated with decreased expiratory reserve volume, functional capacity and respiratory system compliance. In patients with increased abdominal obesity, pulmonary function is further compromised in supine patients by decreased aphragmatic excursion, making ventilation more difficult. Furthermore, increased inflammatory cytokines associated with obesity may contribute to the increased morbidity associated with obesity in COVID-19 infections.

Sudden and Complete Olfactory Loss Function as a Possible Symptom of COVID-19: This is a case study of a patient infected by SARS-CoV-2 whose presenting symptom was the sudden and complete loss of the ability to smell.

Loss of smell and taste in combination with other symptoms is a strong predictor of COVID-19 infection:  “Our study suggests that loss of taste and smell is a strong predictor of having been infected by the COVID-19 virus. Also, the combination of symptoms that could be used to identify and isolate individuals includes anosmia, fever, persistent cough, diarrhoea, fatigue, abdominal pain and loss of appetite.”

COVID‐19 Related School Closings and Risk of Weight Gain Among Children:  “In short, we anticipate that the COVID‐19 pandemic will likely double out‐of‐school time this year for many children in the U.S. and will exacerbate the risk factors for weight gain associated with summer recess.”

Should COVID-19 Concern Nephrologists?  Why and to What Extent? The Emerging Impasse of Angiotensin Blockade:  This is the easiest-to-understand review of the science of this extensively studied virus I have been able to find.  It covers the basics along with detailed explanations of what this virus does, how it works, and where vaccines might operate.    To penetrate human cells, this virus seems to hijack a particular enzyme in the complicated renin-angiotensin system that regulates body fluid balance and blood pressure.

Despite these differences, several studies have reported that SARS-CoV-2 exploits the same membrane-bound angiotensin-converting enzyme 2 (ACE2) as SARS-CoV to gain access to its target cells, although it has greater binding affinity. ACE2 is a carboxypeptidase that preferentially removes carboxy-terminal hydrophobic or basic amino acids. ACE2 cleaves a single residue from angiotensin I (Ang I), generating Ang 1–9, and a single residue from angiotensin II (Ang II) to generate Ang 1–7, whose vasodilator, anti-proliferative, and anti-fibrotic functional effects oppose those of the Ang II generated by angiotensin converting enzyme (ACE).

Jan 24 2020

Weekend reading: Nature Food

It’s pretty exciting when a major international science journal starts a satellite journal devoted to food issues.  Welcome to Nature Food.

Volume 1 Issue 1Silos and systems: The image of a corn processing plant with storage silos represents an early stage of the food supply chain and entry point to a complex, increasingly globalized food system with broad health, economic, social and environmental interactions. The journey from silo to system starts here.

Here’s what’s in Volume 1, Issue 1, January 2020:  

  • Editorial: From silos to systems.  The global food system needs a radical overhaul to sustainably feed 10 billion people by 2050. Nature Food calls on scientists from the many disciplines of food to contribute their knowledge and experience to a collective dialogue on food system transformation.
  • Comment: Planet-proofing the global food system  Without a great food system transformation, the world will fail to deliver both on the United Nations Sustainable Development Goals and the Paris Climate Agreement. There are five grand challenges to be faced, by science and society, to effect that transformation.  Johan Rockström et al.
  • Comment: A national approach for transformation of the UK food system: Transformation of the food system at the national scale requires concerted action from government, business and civil society, based on sound evidence from the research community. A programme for transformation of the United Kingdom’s food system, for healthy people and a healthy environment, is described here.  Riaz Bhunnoo  & Guy M. Poppy.
  • Comment:  A future workforce of food-system analysts:  A programme developed across five UK universities aims to equip graduate professionals with the skills, tools and capabilities to better understand and manage food-system complexity for food security, for the environment and for enterprise.  John Ingram, et al.
  • Q&A:  Where there is political will, there is a way.  Tom Arnold has a wealth of experience in humanitarian and development approaches to combatting hunger. In his roles in food and agriculture, including with Scaling Up Nutrition and Task Force Rural Africa, he advocates for policy consistency and supportive relationships between civil society, business and government.  Anne Mullen.
  • News & Views: Uncertainties in global crop modelling.  A consistent global gridded multi-model assessment of wheat production under climate change points to large uncertainties arising from crop models, particularly in mid and high latitudes.  Ann-Kristin Koehler
  • News & Views:  The changing nature of our food systems.  The wealth of national food supply data, collected over decades by member states of the Food and Agriculture Organization, provides intriguing insights into regional transitions.  Roseline Remans
  • News & Views:  Running AMOC in the farming economy.  Climate tipping points, such as the collapse of the Atlantic Meridional Overturning Circulation (AMOC), could drive significant structural changes in agriculture, with profound consequences for global food security.  Tim G. Benton
  • News & Views:  From stinkweed to oilseed.  Up to now, creativity, ingenuity, time and more than a little luck have been essential for transforming a wild plant into a new food crop. Building on the understanding of gene function in Arabidopsis, the process of domestication can be rapidly accelerated.  Anne B. Britt
  • News & Views: Mind the (supply) gap.  The gap between global supply and demand of omega-3 fatty acids is twice previous estimates. Opportunities to narrow that gap include increasing use of fishery by-products and reducing food waste.  Brett D. Glencross
  • Perspective:  Nitrogen pollution policy beyond the farm.  This Perspective builds on the concept of full-chain nitrogen use efficiency to propose policy interventions and criteria that target major actors in the agri-food chain.  David R. Kanter et al.
  • Perspective:  The unmapped chemical complexity of our diet.  Advances such as machine learning may enable the full biochemical spectrum of food to be studied systematically. Uncovering the ‘dark matter’ of nutrition could open new avenues for a greater understanding of the composition of what we eat and how it relates to health and disease.  Albert-László Barabási et al.
  • Review Article:  The nexus between international trade, food systems, malnutrition and climate change.  Trade agreements can constrain or enable governments’ ability to implement food system-level actions aimed at improving nutrition and mitigating climate change. The technical and political aspects of trade agreements that interact with food systems are reviewed here, and the coherence between trade policy goals and public interest goals, such as nutrition and climate change, is discussed.  Sharon Friel et al
  • Brief Communication:  Systems approach to quantify the global omega-3 fatty acid cycle.  Omega-3 fatty acids are important for the human diet and for some aqua and animal feeds. This study reports a supply gap, and using quantitative systems analysis identifies targets for increasing efficiency in the global omega-3 cycle.  Helen A. Hamilton et al.
  • Article:  Multidimensional characterization of global food supply from 1961 to 2013.  Food systems are increasingly globalized and interdependent. Using food supply data from over 170 countries, Bentham et al. characterize global patterns of food supply change over five decades, highlighting the decline in the supply of animal source food and sugar in many Western countries, the increase in the supply of such foods in Asian countries and remarkably little change in food supply in the sub-Saharan Africa region.  James Bentham et al.
  • Article: Shifts in national land use and food production in Great Britain after a climate tipping point.  Collapse of the Atlantic Meridional Overturning Circulation (AMOC) will impact agricultural land use and its economic value in Great Britain. Ritchie et al. model the impacts of smooth (conventional climate change) and abrupt (tipping point change) AMOC collapse on land use, arable farming and related economic outputs in Britain, as well as the economic feasibility of technological adaptations such as widespread irrigation. Paul D. L. Ritchie et al.
  • Article:  Identification and stacking of crucial traits required for the domestication of pennycress.  Thlaspi arvense (pennycress) has the potential to provide new sources of food and bioproducts when grown as a winter cover crop. Here, Chopra et al. demonstrate that multiple desirable traits can be stacked to rapidly domesticate pennycress. The resulting crop integrates into current crop rotations and produces seeds with improved nutritional qualities, easier harvesting and suitability for human consumption.  Ratan Chopra et al
  • Food for Thought:  The Londoner’s meal.  Globalization transforms societies, economies and cultures. As a subject, food allows us to draw unique narratives on these transformations . The history of pie and mash, also known as the ‘Londoner’s meal’, is such a story of globalization.  Ronald Ranta
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Sep 30 2019

Eat as much meat as you like? Really?

The press release from the Annals of Internal Medicine arrived last week under embargo, sent to me by several reporters: “New guidelines: No need to reduce red or processed meat consumption for good health.”

The press announcement was accompanied by 5 review papers, a sixth with this recommendation, and an editorial.  These are posted on the website of their publisher, the American College of Physicians, implying this organization’s endorsement of this guideline.

Collectively, these papers challenge dietary advice to eat less processed meat and red meat on the grounds of inadequate science.

These papers argue:

  • Eliminating processed and red meat from the diet may reduce disease risks but the effects are small and evidence for them is of low quality and low certainty.
  • Omnivores are unwilling to eat less meat.
  • If you continue to think eating meat is bad for you in the face of this evidence, you are a victim of the “the less you know, the more you hold to your beliefs” syndrome.
  • You can ignore dietary guidelines (regardless of source) and continuing eating meat as you always have.

This is a good example of what I call nutritional nihilism, an approach that insists that because observational studies are based on self-reported information and necessarily flawed, their conclusions are unscientific and should be discounted.  Therefore, because we can’t do more rigorous studies, we should not advise the public about diets best for health or the environment.

I have several concerns about all this:

  • Yes, the effects are small but that is true of nutrition studies in general.  The small effects show benefits from eating less meat.  The authors could easily have interpreted their work as suggesting that eating less meat might be useful.  This is an example of interpretation bias.
  • The authors took a strictly science-based approach to a problem strongly affected by social, economic, and political factors and values.
  • The studies look at previous studies that compared people who eat meat to those who eat less. The authors excluded studies of vegetarians compared to meat-eaters.
  • They look at meat outside its context of calories.
  • The authors did not look at the totality of the evidence; they excluded laboratory and animal studies that can be more closely controlled.
  • They excluded studies of environmental impact, which has a significant bearing on human dietary practices (meat production adds more greenhouse gases than vegetable production).
  • The conclusions fall into the category of “everything you thought you knew about nutrition is wrong.”  This rarely happens.  Science usually works incrementally, not in one enormous reversal like this.

Do the authors really believe that all those other committees and commissions urging less meat were wrong and continue to be wrong?   Their strictly science-based approach seems unrealistic.

The papers come across to me as a concerted attack on dietary guidelines (national and international), on nutrition science in general, and on nutritional epidemiology in particular.

The meat industry and its supporters will love them.

Attacks on the quality of nutrition research have been coming from many sources lately: the food industry, of course, but also statisticians (John Ioannidis at Stanford is making a career of this), and some scientists (usually with ties to food companies).  The criticisms themselves are not new.

What is new is the vehemence and level of effort to discredit observational studies, particularly those based on self-reports of dietary intake.  Yes, nutritional epidemiology has flaws, but the methods have been useful in many instances, as argued convincingly by two of its leading practitioners.

In looking at nutrition research, I think it is essential to evaluate the totality of information available: laboratory, animal, human epidemiology and clinical studies—and to do this in the context of what people actually eat and the number of calories they consume, as well as adding in a hefty dose of common sense.

Common sense is what’s missing in these studies.  Do the authors really believe that:

  • Meat eaters are healthier than vegetarians?
  • Eating more meat is better for health?
  • Meat eaters are less obese and have less heart disease and cancer than those who eat less?

If not, the conclusions make no sense.

Most of the authors report no financial ties to the food industry.  I would love to know the back story about why they chose to do these studies and to interpret them in this way.

Reactions (I will be adding to this list as they come in)