It is human nature to continually want to improve things. In a great many cases, when our knowledge was sufficient and the universe unfolded as expected, our efforts led to social, material and medical advances that have stood the test of time. In other cases, rather than delivering the expected benefits, these innovations led to unintended consequences that plagued us for long periods before we discovered the true nature of their effects and dispensed with them. One of the areas of interest that has seen a great many of these dilemmas has been the field of food and nutrition.

The ancient Greeks and Romans discovered that when they coated the interiors of their copper or bronze cooking pots with lead, many of the food and beverages they prepared tasted much better. Nowhere was this more evident than in the preparation of acidic products such as wines. Popular recipes of the day called for the boiling of the must from grapes in lead-lined vessels in order to prepare a liquid additive that would enhance the color, flavor and shelf life of wine. The resultant sweet, syrupy liquid was called “sapa”.

Sure, they could have added natural honey as they had for centuries, but this new development was considered a real advancement. What actually happened when they boiled the must in lead vessels was a reaction between the acetic acid from the grape ferment and the lead of the pot to form a compound called lead acetate. Lead acetate is also called ‘lead sugar’ because it is so sweet and it made wine more tasty.

What they did not know was that lead sugar was toxic - not the acute toxicity that could be detected immediately - but the chronic toxicity which often evades immediate notice. Thus, the unintended consequence of lead poisoning ushered in an epidemic of morbidity and mortality that lasted for more than 1500 years before being discovered . Unbelievably, this new development in taste contributed significantly to the downfall of Rome, because more than two thirds of the leading Roman aristocrats who served between 30 – 220 C.E. including all the Roman Emperors, were most likely victims of lead poisoning .

In the current rush to replace salt (sodium chloride) in our diet with chemicals that mimic its taste, we may be seeing "déjà vu, all over again." Salt replacement is a very complex task because nothing quite duplicates its taste perfectly. For example, not only does potassium chloride have a considerably lower taste intensity, but it has a large bitter component that has to be compensated for. To get over the bitterness, chemicals such as 2,4-dihydroxybenzoic acid have to be added. But it doesn't stop there because the low-level of salty taste inherent in all the proposed salt replacers require that they be enhanced through the employment of chemical enhancers such as inosine 5-monophosphate, disodium guanylate, glycine monoethyl ester, ornithyl-β-alanine, L-arginine or (N-(1-Carboxethyl)-6-hydroxymethyl-pyridinium-3-ol) commonly known as alapyridaine.

In the past, these industrial chemicals have been approved as additives with the understanding that they would be used in minute amounts within our foods. However, if they are to be used to replace salt throughout our food system we will consume a lot more of them than ever anticipated. Unless long-term chronic toxicity testing of these chemicals is carried out, we may very well be exposing ourselves to the unintended consequences that have befallen humankind in the past. In fact, it is strange that consumer advocacy groups such as CSPI have not questioned their use more closely.

Of course, in more recent history, we have seen the good intentions of trying to eliminate all forms of fat in our diet. Unfortunately, good intentions may not have been enough, because we are now coming to realize that the whole genre of no fat, low fat and reduced fat foods may have contributed significantly to the epidemic of obesity we now see all around us.

Before we go grabbing at another dietary gold ring, it may be prudent to get all our knowledge in place if we want the universal to unfold as it should.

German bakers are up in arms, reports Judy Dempsey in the Feb. 26 NY Times .

European Union officials have offered to sit down with German bakers in an endeavor to defuse the latest uproar over proposed regulations from Brussels.

Echoing a recent furor over legislation dictating the size, shape and texture of fruits and vegetables, German bakers have criticized a proposal that would force a change in the salt content of their products.

The anger of the bakers — who condemned the bureaucrats in Brussels as “taste police” — seems to reflect a rising resentment of the European Union by a country that has long been among its biggest supporters.

The bakers' association declared:

“What the E.U. is doing amounts to stupid interference. ... “The E.U. is trying to change the way we bake our bread, change the way we market it — and of all things, change the taste of our bread. And all this is taking place just months before we go to the polls to elect a new European Parliament. This is exactly the kind of interference and overregulation by Brussels that annoys citizens and even makes the E.U. unpopular.”

This is noteworthy on two counts:

1. Until now, food companies in Europe and North America acted like lapdogs of the food police, failing to challenge the fundamentally-flawed science behind "healthy" food definitions and taking the stance that food manufacturers can avoid being tarred for destroying their customers' health by rolling out new "healthy" foods; and
2. The bakers' lobbying group, the Central Association of German Bakeries, has developed a new line of defense: preparing low-salt breads as the EU wants is energy inefficient, "undermining its goal of improving energy efficiency." The article quotes a Bavarian bakery spokesperson declaring: "We are being asked to change our recipes by reducing the level of salt. But that means we will have to bake the bread for longer and use more energy."

We don't know the validity of the energy efficiency argument, but it's heartening that food companies are awakening to the insatiable bureaucratic appetite for regulating personal dietary choices.

Medical science is evolutionary. We learn as we go and adjust our remedies as we better understand the problems we confront. Guidelines for medical practicioners and for consumers can help us make intelligent choices, but their credibilty can be jeopardized if they stray from recounting the scientific data into the minefield of promoting the policy preferences of the expert scientists who draft the guidelines.

We can and should preserve the credibilty of guidelines by injecting them with a healthy dose of humility.

Scientists have developed a system to grade the guidelines based on the quality of the evidence supporting the advice. The process is as valuable for clinical advice given in the doctor's office as it is for general population advisories such as the Dietary Guidelines for Americans.

The February 25 issue of the Journal of the American Medical Association contains an important article by Pierluigi Tricoci et al which grades the evidence underlying the joint cardiovascular practice guidelines of the American College of Cardiology and the American Heart Association. The results were important in their own right. Authors from Duke University and the University of North Carolina agreed that most of the guidelines are based on "lower levels of evidence or expert opinion" and disturbingly documented that "(t)he proportion of recommendations for which there is no conclusive evidence is also growing." Nearly half (48%) of the guidelines were based solely on expert opinion, not data. And, an icreasing percentage of guidelines are not based on "Class I" evidence but more on "Class II" which are supported by "conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment." Fully 41% of the ACC/AHA guidelines are based on contentious Class II evidence.

The authors called for a more evidence-based approach.

We agree. The background discussion of the paper should be required reading for all expert groups preparing guidelines. After all, at least the ACC and AHA report that their recommendations are based on "Level of evidence C" -- expert opinion, the lowest level of evidence after "Level of evidence A: recommendations based on evidence from multiple randomized trials or meta-analyses" or "Level of evidence B: recommendations based on evidence from a single randomizd trial or nonrandomized studies."

In contrast, the process of preparing the Dietary Guidelines for Americans is purely "Level of evidence C: recommendation based on expert opinion, case studies, or standards of care." Sure, the experts select evidence of quality scientific studies, but the process is inverted: their cited literature follows the experts' conclusions (level C) rather than drive the process (levels A and B).

In an accompanying editorial , Terrence M. Shaneyfelt and Robert M. Centor opine:

Current use of the term guideline has strayed far from the original intent of the Institute of Medicine. Most current aticles called "guidelines" are actualy expert consensus reports. ...

The overreliance on expert opinin in guidelines is problematic. All guideline committees begin with implicit biases and values. However, bias may occur subconsciously and, therefore, go unrecognized. Converting data into recommendations requires subjective judgments; the value structure of the panel molds these judgments.

While many focus on direct financial conflicts of interest as the motivating bias of experts, Tricoci et al dig a bit deeper:

Recommendations based only on expert opinion may be prone to conflicts of interest becaue, just as clinical trialists have conflicts of interests, expert clinicians are also those who are likely to receive honoraria, speakers bureau, consulting fees, or research support....

The list could be much longer and include career and other professional advancement considerations.

The overall message is one of humility and restraint. Don't over-interpret the evidence and fit the evidence to desired policy options. That's what robs guidelines of credibilty and leaves practicioners and the general public whip-sawed with conflicting advice.

For guidelines on dietary salt, the lesson is that we need to adhere more faithfully to an evidence-based approach embodied in the approaches of the international Cochrane Collaboration and the U.S. Preventive Services Task Force, both of which have concluded there is insufficient evidence to justify a population guideline on salt intake levels. That's a "Class I, Level of evidence A" conclusion we should incorporate.

The article and editorial are timely for two reasons:

1. One of the authors, Dr. Robert Califf of Duke University, is reportedly a top contender to become the new Commissioner of Food and Drugs in the Obama Administration and
2. The Dietary Guidelines Advisory Committee has just begun a periodic reassessment of the Dietary Guidelines.

Our vote is for Dr. Califf to head FDA and for a new measure of data-driven humility in rendering dietary advice on Americans' eating habits, converting the Guidelines from expert opinion to a true evidence-based product.

George Will's column today, "Bon Appetit ," his reader-voted best column so far this year, explores the thesis of Stanford University/Hoover Institution fellow Mary Eberstadt that human appetites for food and sex are polar opposites. Intriguing speculation.

The argument runs that a half century ago, people were uptight about sex and casual about their diets while today the reverse is true.

Surely we'll all accept that humans are hard-wired to consume food and enjoy sex, both are essential to our survival as a species. But Will's (and Eberstadt's) thesis that social mores are the driving force in determining the level of indulgence -- the appetite -- may be misplaced. At least for food.

Research published a year ago in Experimental Physiology -- and being studiously ignored by today's dietary morality enforcers -- shows that, at least in the case of "salt appetite," consumption of given dietary intake levels is an unconscious process driven by the brain, not a conscious behavioral choice by consumers.

Theories are stimulating. Data are controlling. That's why human physiology trumps dietary guidelines and why Americans (and others around the world) are eating the same amount of salt today as they did a century ago -- before the food police arrived on the scene to render assistance.

John Tierney's Science column in yesterday's New York Times , is yet another reminder of the problems we're having sorting out scientific fact from scientists' opinion. Tierney takes his cue from the new book, The Honest Broker , by Roger Pielke, Jr. who asks: can scientists be honest brokers? Pielke's concerned that scientists are "jeopardizing their credibility while impeding solutions to problems."

Tierney notes how Pres. Obama's new Energy Secretary and National Science Advisor have both made extremely radical "scientific" doomsday predictions (e.g. no farms in California by the end of the century and a billion deaths from climate change-induced famines by the year 2020, respectively) and recounts Pielke's analysis that scientists think they have two roles: pure researchers or experts providing evidence for political decisions:

A scientist can enter the fray by becoming an advocate for certain policies, like limits on carbon emissions or subsidies for wind power. That’s a perfectly legitimate role for scientists, as long as they acknowledge that they’re promoting their own agendas.

But too often, Dr. Pielke says, they pose as impartial experts pointing politicians to the only option that makes scientific sense. To bolster their case, they’re prone to exaggerate their expertise (like enumerating the catastrophes that would occur if their policies aren’t adopted), while denigrating their political opponents as “unqualified” or “unscientific.”

“Some scientists want to influence policy in a certain direction and still be able to claim to be above politics,” Dr. Pielke says. “So they engage in what I call ‘stealth issue advocacy’ by smuggling political arguments into putative scientific ones.”

When experts disagree, too often the result is name-calling, not resort to hard scientific data.

We've seen that in spades in the discussion of salt and health policy. We need to elevate science to its proper role in sorting out facts, not muddy the waters with expert opinion self-proclaimed as "science."

Put another way, as it is titled in an editorial in February's PLosMedicine: "An unbiased scientific record should be everyone's agenda ." Absolutely.

Recognizing that authors and publishers have built-in biases, the editorial identifies five problem areas:

1. "Journals generally have policies regarding declaration of competing interests by authors. Similarly, editors’ political and scientific views, personal relationships, and professional and financial interests can all conceivably interfere with the objectivity of their decisions."
2. "So much has been published relating to the damaging nature of commercial competing interests that it is tempting to ignore the influence of non-commercial interests in research. Yet publications can be influenced by the desire to promote an idea, or a research program, rather than a commercial product."
3. "All contributors to the debate agree on one thing: a transparent declaration of author contributions is an essential requirement. As part of such a transparency policy, editors can therefore ensure that the individuals responsible for essential roles in research (such as designing the project, carrying out analyses, and writing the paper) are actually named, and their roles and competing interests made clear in the publication."
4. "Many journals now have policies requiring, or recommending, the submission of original protocol documents before papers reporting the results of clinical trials are peer reviewed....these policies enable verification of the study’s prespecified objectives and analysis plan, and require clear description of any subsequent changes."
5. "Editors have an important role to play in encouraging authors to value their results, irrespective of the study’s outcome. For example, in an attempt to impress editors with the importance of a study, authors may overemphasize an intriguing post-hoc subgroup analysis, or may avoid stating that a well-conducted trial was inconclusive in its primary outcomes. Editors can help combat this problem by emphasizing to authors that their data are still publishable if overstated conclusions are appropriately toned down."

We stand with the editors who conclude:

Peer-reviewed publication is the final, essential step in any research project, providing legitimization and credit for the work that has been done. It is the responsibility of everyone involved to ensure that the published record is an unbiased, accurate representation of research. We recognize that today there are many, and increasing, pressures on authors and journals to bias this record. If this pressure is not resisted, journals may increasingly become closer to works of fiction telling the stories dictated by various lobbies rather than works of science. We hope that PLoS Medicine’s efforts, and those of many other journals, to promote full transparency will ultimately lead to a more rigorous and unbiased knowledge base.

A study just published in Hypertension documents that continuous activation of the renin-angiotensin system impairs cognitive function in mice. In humans, low-salt diets reliably predict increased activity of the renin-angiotensin system. The body produces these neurohormones when it senses inadequate salt intake -- and that "inadequacy" is far, far above the IOM's "adequate intake" level for sodium. Low-salt dieters can be assumed to have continuously high renin-angiotensin activity levels.

Other studies have suggested low-salt diets may produce mental impairment. This could be the mechanism.

All this is in addition to the contributions of iodized salt, the consensus solution to overcoming the most easily-prevented, but still-widespread cause of mental retardation: iodine deficiency

Several years ago, the massive Women’s Health Initiative examined the health outcomes of hormone replacement therapy (HRT) where post-menopausal women received supplemental estrogen. “Everyone” knew it was safe and it made logical sense: after menopause, women didn’t produce estrogen so, “of course,” replacing the hormone would make them healthier and live longer lives.

Only it didn’t.

Results of the trial showed clearly that many women died from the treatment. Surprise. The embarrassed NIH quickly shut off that portion of the trial and doctors were warned that what “everyone” knew was the right treatment regime was, in fact, endangering the lives of their patients.

The Salt Institute has cited the incident as a “learning experience” for public health policy-makers: that sometimes the most obvious and popular health nostrum turns a cropper so prudence dictates reserving population health interventions to those that have been tested in controlled trials. HRT never had been tested before it was rushed into practice. “People are dying. We can’t wait,” cried advocates.

Well it’s happened again. Same study. Different health outcome. A study published in the New England Medical Journal February 5 found increased incidence of breast cancer in HRT-treated women “suggesting a cause-and-effect relation between hormone treatment and breast cancer.”

Coming close on the heels of two studies done in Italy that found Coronary Heart Failure patients receiving salt-reduced diets (because for the past century “everyone knew” they work or at least cause no harm) suffered massively greater mortality than those on regular salt diets, the new HRT study drives home the point made repeatedly by the Salt Institute: we need a controlled trial of the health outcomes of low-salt diets. We should not ask the population to be the guinea pigs as we did the women in the Women’s Health Initiative.

Elsewhere we report the news that the European Union is cracking down on food health claims, approving only 9 of the first 43 evaluated and imposing stricter-than-FDA standards, usually based on "convincing" evidence from human clinical trials.

We applaud EFSA for its professed objective of preventing unproven health claims on food labels that would further confuse consumers in making informed dietary choices. To do the job right, EFSA has addressed one critical element: reliable, high quality data should be required to support approved health claims. There is a second crucial standard EFSA should also address: health claims should be based on disease outcomes, not intermediate variables, risk factors or biomarkers -- hard outcomes like disease-caused events or mortality.

On the first point, data quality, the key is to adopt a process like "evidence-based" medicine as defined by the Cochrane Collaboration: first set the standard for quality before looking at what the evidence might be; that's exactly the opposite of what the US Dietary Guidelines Advisory Committee is doing in its expert-based review (which it also calls "evidence-based").

For the second point, the key is to stop looking at "indicators" and "risk factors," recognizing that there are often multiple and conflicting bodily processes affected by any single nutrient. Not only is a carefully controlled trial needed to isolate those effects, but its is their combined totality that concerns us: does the intervention improve health, extending healthy lives, or just change one risk factor (ignoring others)?

With regard to salt, the implications are enormous. The Cochrane Review on health outcomes of salt-reduced diets finds insufficient evidence of improved health to justify a population advisory (as has the US Preventive Services Task Force). That much is clear, though ignored by diehard salt reductionist activists like WASH and its most vocal advocate, Dr. Larry Appel. It is the second question that will prove pivotal for EFSA if it hews consistently to the high standard it professes. For salt, the proper measure is cardiovascular health. Not blood pressure. Not insulin resistance. Not neurohormonal activity. All of these are risk factors. Some "improve" in some people when they reduce salt. Others impose additional risks when salt is reduced. It is the net effect -- the health outcome -- that is important.

In the US, FDA has wandered off into the health policy wilderness on this point. Its health claim (whatever one's view of its scientific rigor, the subject of another discussion) is for "hypertension," a risk factor, not "cardiovascular health" (or heart attack incidence, another "hard outcome"). FDA could just as well approve a health claim that diets with today's salt intake levels protect insulin resistance and warn consumers of the fact that salt-reduced diets endanger our ability to metabolize glucose properly, setting up low-salt dieters for diabetes and metabolic syndrome. For FDA to follow the professed EFSA approach, it should replace a "salt and hypertension" health claim with one for "salt and cardiovascular health" -- but then, of course, back to point one, quality of evidence, there would be insufficient evidence to support such a claim.

The challenge for EFSA is to resist the blandishments of the salt reduction lobbyists who claim to "know" that their computer-modeled extrapolations of blood pressure changes due to salt intake levels represent true health outcomes. EFSA should insist not only on good quality science, but on evidence that an intervention (or food) will actually improve HEALTH.