Jane Brody, Dietary fat and carbohydrate, Vitamin D and really assessing the evidence

I admit that, as I write this, it is hard to think of anything else as important when Vladimir Putin has invaded Ukraine in an action that, in addition to its obvious direct impact on that country, had led to as great a threat to nuclear war and human extinction as we have seen in two generations. That a deranged power-mad autocrat can do this is even more terrifying when we look at the number of psycho autocrats that have gained power in the world, including recently (and hopefully not in the future) in the US. But I am not going to write about it, for three reasons:

--It is not the topic of this blog, which is Medicine and Social Justice

--There remain a lot of things that urgently need discussion in regard to American healthcare, mired as it is not only in the evils of for-profit capitalism but incredible inefficiency and incompetence, and

--These issues actually matter on a day-to-day, week-to-week, year-to-year basis for the American people.

First, I will start a good thing, or at least a mixed one. The less-good part is that Jane Brody, the health columnist in the New York Times, has written her last column. The good part is lauding her for the incredible contributions she has made to our understanding of the issues of our health over the decades (since 1976) that she has been writing it. We all have (or should have) learned much from her, about diet, and exercise, and dealing with illness and even death. In her last column she points out some areas where her advice has been incorrect, based on the science of the time, when new evidence has disproven it. I believe that an ability to acknowledge that you were wrong, whether because (as usually true for her) the scientific knowledge has changed, or because you wanted to believe something and so were previously unwilling to actually examine the evidence adequately. A particular area of health that she has been associated with is diet (she has written several cookbooks), and this is the area in which her admission of error is most incomplete and thus disappointing. While she notes that ‘One of the most significant shifts has concerned dietary fats,’ her emphasis is on how the recommendations in the ‘70s to shift away from animal fats missed the dangers of vegetable-based trans fats. She cautiously says ‘But time will tell whether specific dietary fats, or the much vaunted Mediterranean diet currently embraced by many doctors, will fall prey to future findings.’ 

But that’s it. There is no mention whatever of the problems with carbohydrates in the diet, particularly simple carbohydrates like sugars, on people’s health. This is a major lapse. Without getting into a discussion about the benefits of a very-low-overall carbohydrate diet (e.g., Atkins, paleo, etc.), there can be no question that large amounts of sugar (and possibly even small amounts of sugar) in the diet is deleterious, non-nutritious, and causes not only obesity but a great many other health problems, and that no reasonable diet today can fail to feature this fact. Moreover, it completely avoids the evidence that the campaign against dietary fat, carried on by organizations such as the American Dietetic Association (now the Academy of Dietetic and Nutrition, AND) and many others, for decades was funded by the sugar industry and the manufacturers of high-sugar foods such as soda pop (addressed in several blog posts, including Gangster capitalism and our health: In the US and in the World Jan1, 2019, The AAFP, Coca-Cola, and Ethics: Serving the public interest? Aug 20, 2010, and others). The lack of any mention of this in Ms. Brody’s column is concerning; does she still believe that fat is a bigger dietary problem that sugar? This is not an academic question; go to your grocery store and look at the labels on “low fat” or “fat free” products and see what is in them. My personal favorite is “fat-free half-and-half”, which is almost an oxymoron because fat is the basis of half-and-half: half whole milk (4% fat) and half cream (about 20%) for a total of about 12%. How can half-and-half be fat free? Read the label! It is full of sugars. Indeed, almost all foods with such labels are high in calories an high in carbohydrates, especially sugar (commonly in the form of ‘high-fructose corn syrup’).

Another undying health claim, promoted by some doctors and many non-medical professionals and non-scientists for several decades is vitamin D (not an issue which Ms. Brody, in this final column, addresses). Fifteen years ago, endocrinologists were promoting vitamin D deficiency as a major endemic problem, claiming deficiency at blood levels then (and now) considered normal. While most have backed away from the idea that it is a panacea, some have not and fed an ongoing commitment to taking more of this vitamin, an idea that flourishes on, of course, the Internet. With the onset of the COVID-19 pandemic, enthusiasts have found this to be the newest “indication” for it (Vitamin D, false nostrums, and conspiracy theories: The world has enough real problems, Jan 28, 2021). In an excellent – and brief and easy to read --Commentary on Medscape® (Feb 17, 2022), John Mandrola asks ‘Why Is Vitamin D Hype So Impervious to Evidence?’. His emphasis is on critical appraisal of the scientific research, on the quality, breadth, and significance of the studies done. He emphasizes that there are many, many randomized controlled trials that do not show that taking Vitamin D decreases the risk of any condition (other than true vitamin D deficiency, which occurs at quite low levels.) Among the many important points he makes is that association (many people with chronic disease have lower vitamin D levels) does not show causation (it was the low vitamin D levels that caused the disease), because often ill-health causes the lower levels, and still less that administration of vitamin D will cure it. Indeed, he discusses the many large, well-designed studies that prove that it does not.

So why is this issue so impervious to evidence? The answer, it appears, is rooted more in psychology than science, in how people choose to believe what they believe and seek out evidence that supports it (if, indeed, they seek evidence at all). There are always experts who espouse their (and almost any) position. Even when they are a small minority, there are 330 million Americans and 8 billion people in the world, so a small minority can be a lot of people. Almost all people (scientists are a very small minority) do not have the training or the skill to read and assess the scientific literature, and it is uncommon that they even try. Instead, they seek (or have sent to them) articles by people that seem to be reputable that support their position. Mandrola focuses also on how even scientific papers engage in “spin”, pointing out how often they emphasize minor, secondary, and non-significant results even when the main point that they were trying to prove (that vitamin D cures or prevents something) is not shown by their research. Indeed, such minor things are pounced on by a public that wants to see what isn’t there; he gives this example:

the authors of the VITAL trial, which found that vitamin D supplements had no effect on the primary endpoint of invasive cancer or cardiovascular disease, published a secondary analysis of the trial looking at a different endpoint: a composite incidence of metastatic and fatal invasive total cancer. They reported a 0.4% lower rate for the vitamin D group, a difference that barely made statistical significance at a P value of .04. 

But everyone [he says; I think he means physicians and scientists] knows the dangers of reanalyzing data with a new endpoint after you have seen the data. What's more, even if this were a reasonable post hoc analysis, the results are neither clinically meaningful nor statistically robust.  Yet the fatally flawed paper has been viewed 60,000 times and picked up by 48 news outlets. [emphasis mine].

Think about that. It is not what is proven to be true that gets the most coverage, it is what is most provocative. And clearly, this is not just about vitamin D. COVID and the COVID vaccines are common and prevalent examples of people choosing to believe something and then picking and choosing research that supports it; they even call this “doing their own research”. Some of this is the result of religious-like devotion to a position or point of view, some is purposely malicious, some is conspiracy theory, and some is honestly being overwhelmed by data that they do not understand. But it sure can be very dangerous. You deciding that COVID is not a risk anymore (if ever) and you don’t need to be vaccinated and don’t need to wear a mask is dangerous to me!

If over 95% of climate scientists agree that human activity, especially the burning of fossil fuels, is the cause of global warming, but many people do not believe it, why would we think the kinds of foods we eat, the benefits (or not) of taking high doses of a vitamin, the risk of a pandemic virus, the benefit of vaccination, would not be controversial? I would like to agree with Dr. Mandrola that there is hope, but I am sometimes not sure.

In the meantime, get vaccinated, eat very little sugar, and do not overdose on vitamin D, which can absolutely happen.

 

Vitamin D, false nostrums, and conspiracy theories: The world has enough real problems

Near the end of December, Tiffany Hsu, writing in the NY Times, discussed “Dubious COVID Cures”. She compared them to the similar nostrums popularly recommended for the 1918 influenza epidemic, when ‘a spate of ads promised dubious remedies in the form of lozenges, tonics, unguents, blood-builders and an antiseptic shield to be used while kissing.’ She quotes the head of research at MyHeritage, Roi Mandel as saying “So many things are exactly the same, even 102 years later, even after science has made such huge progress.”

Even after all this scientific progress and all the advances in health care, people are still fascinated by over the counter magic drugs, things that seem easy, and are often cheap (although usually very profitable), and somehow better than the treatments being offered by the medical community. This is, of course, even more so when that medical community does not have a whole lot to offer in terms of treatment, a particular issue for virus infection, and mostly talks about prevention, about such things as isolation and physical distancing. Wouldn’t it be better if you could just take something that would cure it or make it better or at least decrease the seriousness of an infection? And, you know, there are ‘studies’ that show it works (although of course I haven’t actually read them and would have no idea how to understand if the research was legit) and, you know, there are doctors who recommend it!  Like ‘Dr. Pierce’s Pleasant Pellets promised that the pills — made from “May-apple, leaves of aloe, jalap” — offered protection “against the deadly attack of the Spanish Influenza.”’ Oh, wait, that was from 1918 – but we have Dr. Oz!

This is not to say that some popular treatments do not have benefit, and this is especially good if they do not harm you, and if they are cheap. One such could be Vitamin D, which has been advocated (most recently for COVID-19, but for a lot of things) by many people, some of whom are actually experts. As with many “natural” remedies, most of the basis for this is in syllogism. You extrapolate from something that is known about a substance (commonly, as in the case of Vitamin D, that it “promotes immunity” – a pretty general, non-specific claim), but such claims are uncommonly backed up by rigorous testing to see if it actually does work. (Freeman’s Second Law: Something that makes sense is properly called a “research question”. You wouldn’t want to study something that didn’t make sense. However, to know whether it is actually true, you have to actually do the studies!)

Recently, The Guardian had an article titled “Does Vitamin D Combat COVID?”. It is very positive about the vitamin, citing many important people (unsurprisingly, being The Guardian, many from England), but does stop short of claiming that it will definitely work. The claims for benefit vary: it makes it less likely that you will get infected, that if you get infected you will get less sick, that if you get sick you are less likely to die. Not really quantified though. The reason is that there are studies that show both benefit and not, and none of them are definitive. There is also concern that people with more melanin in their skin, presumably a genetic adaptation to being from areas with more sunshine (and thus more vitamin D) can become vitamin D deficient when they live in areas in northern latitudes with less sun. Obviously, this is confounded by the existence of a variety of other social and medical health risks accruing to dark-skinned people in northern latitudes. Maybe it is an additional one, but it is unlikely that just taking Vitamin D will solve the problem of inequity.

The actual evidence is summarized in a recent piece in JAMA, “Sorting out whether vitamin D deficiency raises COVID-19 risk”. The first thing that you note here is that it is answering quite a different question – whether people who have low vitamin D levels have greater risk (and, thus, presumably, should take vitamin D supplementation), not whether everyone should be taking vitamin D. ‘Research findings about vitamin D and COVID-19 have been mixed and sparse,’ is the key finding, and the ‘Upshot’ of the pieceis a quote from Dr. Catherine Ross, a nutritionist at Penn State: ‘“Avoiding vitamin D deficiency is always a goal.”’

So you should take vitamin D supplements if you are deficient (Dr. Fauci says this also), although knowing if you are deficient would require both your having your level measured, something which is not recommended by the most reliable source, the US Preventive Services Task Force (USPSTF) for asymptomatic adults (although it is by many who are consultants to vitamin D advocating groups), as well as to know what the level below which you are deficient is: 20? 30? 50? You can find all of these in the “literature”. And it is concerning when advocates have industry ties. Nonetheless, vitamin D is available cheaply and generically, is safe if you don’t take too much (as a fat-soluble vitamin you CAN overdose on it), and Dr. Fauci takes it (same article). I took one this morning.

But the really big question is not vitamin D, even if the evidence is not absolutely clear. Overall, it is pretty safe and pretty cheap and has a conceptual justification and at least some studies show some benefit. The really big issue, as put forth early in this piece, is why do people continue to search for magic treatments that are not mainstream? Why do they often trust their friends and neighbors and strangers on the Internet more than doctors? I don’t know for sure, but in Hsu’s article comparing today to 1918 he quotes Jason P. Chambers, associate professor of advertising at the University of Illinois: “Human beings haven’t changed all that much. We’d like to believe we’re smarter, that we’d be able to spot the lies, but the ability of advertising to maintain its veneer of believability has only become more sophisticated over time.” Unfortunately, we’re probably not. That is why advertising is so successful.

This fear is related to not only mistrust of science (it is hard to understand) but to conspiracy theories in general; recently the “political” belief in a “deep state”, that “they” are lying to us and trying to keep important information and benefits from us. Of course, “they” may be; I certainly do not trust the leadership of our country (or any country) to necessarily work in the best interests of the people, except of the richest, most powerful and well-connected people. I absolutely believe that Big Pharma is only interested in making as much money as possible and selling us drugs which may not be any better than cheaper ones, or none at all. But the suspicion that science and medicine are working to harm us often segues into pretty odd stuff (I was recently sent this nonsense about the COVID vaccine being a plan to engender female sterilization!) (On the subject of conspiracy theories, Andy Borowitz’ recent satire – QAnon merging with the Elvis-is-Alive groups -- is, as usual, not far off the mark.)

I am sure that some of this is the fault of the arrogance of scientists and doctors. A good friend was recently diagnosed with breast cancer and was told by her doctors to “not go on the Internet, to not talk to anyone who has had it, because everyone’s cancer is different”. This is ridiculous, although I understand that they probably get frustrated by people coming up with silly or, worse, dangerous treatment ideas that they have heard from someone, or stories from their sister-in-law’s neighbor. This can of course be much better addressed, with something like “You’ll hear a lot from people who have had breast cancer; it is a common disease. You will certainly look things up on the Internet. Listen to them, but remember you are you, and your experience is not likely to be exactly the same as theirs. Please don’t take any treatments without discussing it with us, so we can make sure there is no danger. Welcome the support.” And, I would be wrong to omit, the big reason that doctors feel so pressured and don’t have enough time to talk to and discuss things with folks is in large part because the big corporations they work for (for-profit or “non-profit”) are about maximizing income, not health.

Still, people seem to find themselves drawn to “alternatives”. They like “natural”. OK, keep your mind open, but remember than “natural” is not necessarily better. Any substance that has any effect, positive, negative, or neutral is because of chemicals in it. That they occur naturally does not make them safer than those that are manufactured.

And watch the conspiracy theories and think about what is important. Life on earth could be extinguished by climate change. That is real. War which leads to nuclear war could do it first. People all over the world are starving, are without housing, without basic health care, subjected to natural disasters and man-made ones. They are being killed, often in genocides. In all countries, including ours, there is structural oppression of people based on race, religion, gender. Wealth is being transferred from regular and even poor folks to the richest at an astounding rate. Authoritarian leaders, and even fascists, are proliferating.

These are real problems, that need real concerted efforts to combat. Work on these. Don’t be distracted by non-issues.

Calcium, Heart Attack and Osteoporosis

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A recent meta-analysis published in the British Medical Journal by Bolland, et. al., finds that there is a 30% increase in the risk of myocardial infarction (MI) in women taking calcium supplements for osteoporosis (“Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis”, BMJ 2010;341:c3691). If supported by other research, this could be big news, as millions of women are doing just that. A few “bullets”:

· 15 studies were reviewed by the meta-analysis comprising comparisons of 12,000 women either taking or not taking calcium supplementation for osteoporosis. For some of these studies results were available for individual women, and some for just the group as a whole, but the results were similar.

· Women receiving calcium had 30% more MIs than those who were not. Other end points: stroke, death from cardiovascular disease, and death overall, did not show significant differences, although they did show trends toward reduction in the non-calcium groups.

· The studies reviewed in the meta-analysis were all of women taking calcium but not taking vitamin D supplementation with it.

· The studies were not done for the purpose of looking at cardiovascular mortality; the data were re-analyzed and other sources of data were used to look at the outcome events.

The authors recommend that women who are taking calcium without vitamin D for osteoporosis stop doing so unless they are also taking a drug that treats osteoporosis, such as a bisphosphonate (which have their own risks, although in women with osteoporosis these are usually outweighed by the benefits) or selective estrogen receptor modulator (SERM) like raloxifene, usually used for breast cancer treatment (links are to a few different websites, including WebMD, FDA, and BreastCancer.org; they are representative although not definitive, and there are, of course, other sites). They note that their results are similar to other studies of women taking calcium alone, although a Women’s Health Initiative (WHI) study on women taking both calcium and vitamin D did not show any effect on the incidence of coronary artery disease. The authors suggest possible reasons for the difference, including protective effects of vitamin D, the younger age of the WHI participants (mean of 62 vs. 75 for the meta-analysis), and the interesting, but slightly confusing fact, that the WHI study had a much higher percent of women who were taking calcium before the study began (“non-protocol”): 54% vs. 1.2%. If taking calcium is associated with more MIs, why would women who were taking more calcium before the study have lower rates? And yet, the authors note that “Interestingly, the only study in our analysis that reported a relative risk of less than 1.0 for myocardial infarction with calcium also had high non-protocol use of calcium supplements.”

In their accompanying editorial, “Calcium supplements in people with osteoporosis”, BMJ 2010;341:c3856), JGF Cleland, K Witte and S Steel go farther than the authors of the meta-analysis, saying clearly in their sub-head “Should not be given without concomitant treatment for osteoporosis”, even when given with vitamin D. Their justification is the lack of good evidence for improved outcomes, including pathologic fractures, with the use of calcium and vitamin D. “Calcium supplements, given alone, improve bone mineral density, but they are ineffective in reducing the risk of fractures and might even increase risk, they might increase the risk of cardiovascular events and they do not reduce mortality. They seem to be unnecessary in adults with an adequate diet. Given the uncertain benefits of calcium supplements, any level of risk is unwarranted.” With regard to vitamin D, they say “Vitamin D supplements might reduce the risk of falls, might have important clinical effects on cardiovascular function, do not increase mortality, and may mitigate the trend to excess mortality seen with calcium supplements alone. However, no conclusive data are available to show that current doses of vitamin D supplements with or without calcium supplements reduce the rates of fracture, and meta-analyses found evidence of substantial reporting bias.”

The editorialists emphasize that while calcium does increase bone density, this is a surrogate variable while the issues of fractures and mortality are the true outcomes, an issue I have addressed several times recently (Rosiglitazone and the "Holy Grail", July 16, 2010; Statins and scientific integrity, July 6, 2010 ). They say “Surrogate measures may be useful in pilot studies but become problematic when they become the goal of treatment.” They are quite rigorous in looking and risk and benefit, noting even that exercise, while perhaps a good way to increase bone strength, “also carries risk”. They cite Kanis, et. al., from 2002[1], but it should be obvious that exercise can have risk.

The last part of the editorial is, however, more concerning to me. The authors call for greater demonstration that drugs will have positive effects on important outcome variables (a good thing) but they then worry that such requirements will be so burdensome as to stifle research: “Requiring companies to show before licensing that treatments for chronic diseases such as osteoporosis, diabetes, and hypertension reduce long term disability and death could lead to a cessation of research in these areas. The cost and commercial risk would be too high.” They then call for an extension of patents on these drugs to 50 years, similar to the Berne convention for copyrights on a song. The presumption is that this would be long enough for the companies to make back their money. Obviously, however, this also means that consumers would have to pay the higher costs for patent, rather than generic-equivalent drugs, for much longer.

Amazingly these authors, despite citing no conflicts of interests (which might explain such a position if they in fact held patents or were being paid honoraria by pharmaceutical manufacturers) dispense with such concerns in a single sentence “Lower prices for innovative drugs could be negotiated.” By whom? How? What would be the effect on the consumer? All I can imagine is that because they are British, and in Britain there is a National Health Service which charges a fixed fee to patients for all drugs, that they are thinking only of cost to the NHS and have no idea how much the cost of patented drugs is to Americans. Which, as Americans know, can be phenomenally high. (Example: generic alendronate, the oldest bisphosphonate, costs roughly $40 a month for either 35mg [recommended for prevention of osteoporosis] or 70mg [recommended for treatment of osteoporosis] per week doses, while the brand name, Fosamax ® costs about twice that; for those not available generically, risendronate (Actonel ®) costs 3 times as much, and ibandronate (Boniva ®) costs about $350 a month; all prices wholesale from ePocrates and www.drugstore.com.) Taking drugs that you need for a chronic disease is very different from downloading a song!

Of course, this is another strong argument for having a national health insurance plan that covers everyone. In the meantime, while we will wait for the certain flurry of responses and comments, not taking calcium unless one is also taking a bisphosphonate or similar osteoporosis treatment drug, seems prudent; taking vitamin D, without calcium, for its other benefits, is probably still a good idea.

[1] Kanis JA, Brazier JE, Stevenson M, Calvert NW, Lloyd JM. Treatment of established osteoporosis: a systematic review and cost-utility analysis. Health Technol Assess 2002;6:1-146.
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