Prof. Dr. med. Robert Heaney
About Dr. Heaney
Robert P. Heaney, BS'47, MD'51, is a clinical endocrinologist specializing in nutrition. Until 2014 He held the John A. Creighton University Professorship. He is world-renowned for providing nearly 50 years of advancements in our understanding of bone biology, osteoporosis, and human calcium and vitamin D physiology.
VITAMIN D AND THE HUMAN FAMILY TREE
Why the Neanderthals Lost the Race
Based on both physical and DNA evidence, anthropologists classify humans as members of the family of great apes, which includes orangutans, gorillas, and chimpanzees, as well as various human species. The branch to which we modern humans belong includes at least six species belonging to the genus Homo whose fossil remains have been found in East Africa over the past 60+ years. There was once a tendency to think of the latter as ancestors of modern humans, as if they were stages up a single branch of the tree, rising from primitive to advanced over hundreds of thousands of years, with Homo sapiens at the very tip, i.e., the "highest" form of human. On the contrary, the human family tree is both more complicated and more interesting. These various other members of the genus Homo are now recognized as separate twigs off the human branch of the great ape lineage. They are not so much our ancestors as our cousins. That branching continued to occur for millennia alongside the twig that we now recognize as modern humans (Homo sapiens). Some of those other humans made it to Europe before we (Homo sapiens) did.
The migratory path of the several human groups took them north out of Africa, then through the Middle East, ultimately colonizing Europe and Western and Southern Asia. Evidence for the European in-migration of Homo sapiens is clear and points to a time about 40,000 to 50,000 years before the present. But that's not early enough to qualify as "first." The discovery of settlements by other species of Homo throughout Europe, extending as far east as Western Siberia (e.g., the Denisovan people, >50,000 yrs ago), indicates that they predated the arrival of Homo sapiens by thousands of years.
The best studied of these earlier migrants out of Africa are the Neanderthals, whose remains and cultural artifacts are found throughout Europe, and who clearly precede the arrival of Homo sapiens. Anthropologists and paleontologists have puzzled over how it was that Homo sapiens, as late arrivers, came to displace the Neanderthals. Many theories have been proposed, ranging from superior weapons and technology to superior intelligence, and most recently to the use of what Scientific American termed "the ultimate weapon," cooperation.
For the most part, these explanations have not been completely satisfying. Nevertheless, one factor does seem certain: Homo sapiens effectively "swamped" the Neanderthals. There were simply many more of us than of them. But that alone does not explain the apparent, complete disappearance of the Neanderthals. DNA evidence indicates that there was some limited interbreeding between resident Neanderthals and immigrant Homo sapiens. So, in one sense, some of the Neanderthal genome has survived. Interestingly, the presence of Neanderthal DNA in the modern human genome, which amounts to something like 2-3 % of the total genome, is largely confined to modern Europeans and Asians, indicating that the interbreeding occurred after the arrival of Homo sp. in the Middle East and/or Europe.
Still, why did the Neanderthals disappear from Europe? Recently, Leonard Greenfield, a physical anthropologist/paleontologist at Temple University, has set forth a persuasive case for a critical role of vitamin D, both in shaping the evolution of modern humans, and in explaining the disappearance of the Neanderthals.It is generally agreed that the ancestral home of all of the various Homo species was East Africa, a location that would have provided abundant vitamin D in the form of sunlight. (Solar UV-B radiation converts a precursor compound into vitamin D.) Contemporary individuals from East African tribes exhibit a vitamin D status, derived mainly from cutaneous synthesis, which is equivalent to what would be produced in a Caucasian by a purely oral intake of 5,000 to 8,000 IU/day. However, it is also known that solar input of vitamin D inexorably diminishes as individuals move north out of equatorial latitudes.Thus north-migrating peoples coming out of East Africa pretty much all faced some degree of vitamin D deficiency.
That fact is generally considered to be the main explanation for the rapid loss of skin pigmentation among the migrating tribes of Homo sp. The heritable mutation that lead to the shift to pale skin thereby enhanced cutaneous synthesis of vitamin D and thus partially offset the diminished solar UV-B irradiance at higher latitudes. Individuals without that change in skin pigmentation would have been even more seriously vitamin D deficient than the others, and their pelvic bone structures could have been so distorted by D-deficiency rickets that delivery of babies from below would have been difficult or outright impossible, leading ultimately to extinction of those tribes and families that failed to develop pale skin.
But that simply means that all migrants coming out of Africa would have had marginal to deficient vitamin D status. The farther the northward migrants got from their place of origin, the worse their vitamin D status. But that tells us nothing about why Neanderthals, particularly, lost the race to survive in Europe. The only sources of vitamin D available to European Homo sp. would have been what little sun exposure might have been available and a diet rich in seafood & marine mammals. The high latitude of most of Europe and its extensive and persistent cloud cover mean that most individuals would have gotten little vitamin D by the solar route, which leaves only food. Greenfield points out that only the Homo sapiens immigrants had developed cultural practices that included fishing and/or eating the meat and fat of marine mammals. As a result, the Homo sapiens "immigrants" would have had been better able to achieve and maintain a healthy vitamin D status than the Neanderthal "natives".
But general health, alone, is probably not a satisfactory explanation for what appears to have been the fairly rapid extinction of the Neanderthals. There's more to the story. Adequate vitamin D status is absolutely essential for an organism to mount an adequate immune response, particularly in the face of foreign antigens, to which the "natives" would have had no prior exposure. (There are many contemporary examples of populations being "wiped out" by infectious diseases with which they had had no experience, brought to them, even if unwittingly, by "discoverers" or colonizers.)
Thus it appears likely that native, Neanderthal populations, would have declined both in numbers and in dominance simply because, unprotected by adequate vitamin D and hence with compromised immune competence, they succumbed to diseases brought to them by the invading Homo sapiens, whose vitamin D status was better and who, in addition, had inherited some degree of resistance to the diseases concerned. Also, as just noted, the invaders had dietary practices that, in comparison to Neanderthals, better suited them to live and thrive in a vitamin D-deprived environment (i.e., fish eating). Presumably, had the resident Neanderthals been able to achieve a more adequate vitamin D status they would have been better equipped to deal with the diseases brought to them by the invading Homo sapiens migrant bands.
There is a moral to this story, namely that nutrition is important after all, not just for the health of individuals, but for the survival of whole populations. But there is yet another insight to be gained. We are able to discern the association between poor population-level survival and low vitamin D status in the Neanderthals, but only from our great distance in time. Individual Neanderthals with inadequate immune competence would have been prone to become sick or to die, but up close one could not have been certain that it was the vitamin D status that was responsible, even if we had been there. Nor would every individual with low vitamin D status have succumbed. There is great deal of variability in sensitivity to, and need for, vitamin D from person to person. It's just that, considering the population as a whole, the risk of a Neanderthal individual's developing one of those unfamiliar diseases would be elevated, and, as a group, Neanderthals would thus be less competitive in a Darwinian sense. This was the reason Greenfield puts forth and it seems the most satisfactory of extant explanations for the fact that the Homo sapiens population grew and prospered, while the Neanderthal population, already fewer in numbers, shrank.
Greenfield, L.O. Vitamin D Deficiency in Modern Humans and Neanderthals. (2015). OutskirtsPress, Denver, CO
The IOM Miscalculated Its RDA For Vitamin D
Posted on February 13, 2015 by Robert P. Heaney
Last year (2014) saw an unusual event. Two statisticians at the University of Alberta in Ednonton, Canada (Paul Veugelers and JP Ekwaru) published a paper in the online journal Nutrients (6(10):4472-5) showing that the Institute of Medicine (IOM) had made a serious calculation error in its recommended dietary allowance (RDA) for vitamin D. Immediately, other statisticians checked the Canadians' analyses and found that, indeed, they were right. Together with my colleagues at Grassroots Health, I went back to square one, starting with a different population entirely, and came to exactly the same conclusion. The true RDA for vitamin D was about 10 times higher than the IOM had said. Not a small error. To understand, how this might have happened and why this is important, some background may be helpful.
An RDA is technically the amount of a nutrient every member of a population should ingest to ensure that 97.5% of its members would meet a specified criterion of nutritional adequacy. For vitamin D, the IOM panel determined that the criterion for adequacy was a serum concentration of a particular vitamin D derivative (25-hydroxyvitamin D) of 20 ng/mL or higher, and that for adults up to age 70, 600 IU of vitamin D per day was the RDA.
Both of those figures provoked immediate and unprecedented dissent from a diverse group of nutritional scientists, but the disagreement centered mostly around the IOM panel's reading and interpretation of the evidence, rather than its calculation of the RDA. The Edmonton statisticians took the dissent a step further, showing that the actual calculation was itself wrong. Here's what seems to have happened.
Not everyone gets the same response to a given intake of any particular nutrient, i.e., some require more than others to reach the specified target, and while the average response to a certain dose of vitamin D may be above the target level, a substantial fraction of a population can still be below it. Thus, the RDA will always be higher than the average requirement, and for some nutrients, substantially so. As a consequence, ensuring that every member of a population receives the RDA guarantees that 97.5% of that population will be getting at least enough, while many will be getting more than they actually need.
The IOM panel identified a number of published studies showing the 25-hydroxyvitamin D response to various vitamin D doses. They plotted the average response in each of those studies against dose, thereby generating what is termed a "dose response curve", i.e., a way to estimate how much of a response would be predicted for any given vitamin D intake. But, to make a long story short, because it used average responses, that curve tells us nothing about the intake requirement for the individual members of a population, and particularly those whose response to a given dose falls in the bottom 2.5 percentiles. The IOM panel surely knew that the average intake required to meet or exceed 20 ng/mL was not the same as the RDA, as it would be inadequate for all those with below average responses (about half the population). So, to catch the "weak" responders, they calculated the 95% probability range around their dose response curve, designating as the RDA the point where the bottom end of that probability range exceeded 20 ng/mL. While this might seem to have been the right approach, it was not. The panel appears to have overlooked the fact that the 95% probability range for their curve is for the average values that would be expected from similar studies at any particular dose. The dispersion of averages of several studies is, as every beginning student of statistics knows, much more narrow than dispersion of individual values within a study around its own average. And it's the 2.5th percentile individual values from those studies, not the study averages, that should have been used to create the relevant dose response curve.
It's this latter approach that the Canadian statisticians used. They took precisely the same studies as the IOM had used and demonstrated that the requirement to ensure that 97.5% of the population would have a value of at least 20 ng/mL, was 8,895 IU per day. Recall that the IOM figure was less than 1/10 that, i.e. 600 IU per day up to age 70 (and 800 IU per day thereafter). When my colleagues and I analyzed the large GrassrootsHealth dataset, we calculated a value closer to 7,000 IU per day, still a full order of magnitude higher than the estimate of the IOM, and not substantially different from the estimate of Veugelers and Ekwaru.
Why This Is A Problem
This is an important mistake, not simply because it shouldn't have been allowed in a major policy document, but because IOM recommendations have important effects on a wide array of government programs. These include nutritional standards for US military, for school lunch programs, for WIC and many others, both in the United States and in Canada.
Canada, which paid one third the cost of generating the IOM report, is in a particularly difficult situation. Its First Nations peoples, living near the Arctic Circle, do not get any vitamin D from the sun, as do those of us living at more temperate latitudes. They are totally dependent upon food and supplement sources. Their ancestral diets, based largely on seals and whales, constituted a rich source of vitamin D. They are much less commonly consumed today, in part because of the ready availability of low nutrient density foods flown in from the south, and in part because environmental pollution has made seal and whale products a source of dangerous toxins (as well as necessary nutrients). The Canadian government, responsible for the health of all of its citizens, can turn only to the existing IOM recommendation (600 IU per day) to set standards for the people living in its northern territories. But, as the Edmonton statisticians noted, that number is woefully inadequate.
There is almost no public awareness of this error or its implications in the United States, but that is not true for Canada. A large nutritional health foundation located in Calgary (Pure North S'Energy Foundation) has taken out a series of half page advertisements in Canada's national newspaper (Globe and Mail), alerting Canadians to the fact that the error was made and that they need more vitamin D than current policy indicates (http://www.purenorth.ca/?page_id=1356). The IOM, Health Canada, and the Canadian Ministry of Health have all been formally alerted to this problem. The Health Ministry has agreed to undertake an independent reanalysis of the calculation of the RDA, but the results are not yet available and the shape of the ministry's action is still uncertain.
How It May Have Happened
It's one thing to know how the mistake was made, and quite another to know how it could have happened. Here, one can only speculate, as the IOM processes are shrouded in secrecy. The IOM report was a massive document and it is likely that much of the background work, such as the literature search, the drafting of the report, and the statistical calculations, were done by IOM staff members who may not, themselves, have been sufficiently expert in the vitamin D field to recognize discrepancies that might have popped up. (It is noteworthy that several of the dissenting letters submitted to scientific publications following release of the IOM report had specifically cited the fact that 600 IU per day was not sufficient to guarantee a level of 20 ng/mL.) It would then have been up to the expert panel to review and adjust this staff work. To be fair to the panel, it is important to understand that the scientific members of IOM panels are not compensated for their time and effort. They do it as a public service, and they are all busy scientists with work of their own. Still, it was their job, and one must wonder how they failed to see an error that was apparent to other equally knowledgeable, but outside, scientists.
There may be a moral here. It is widely recognized that many of the panel members, before coming together to review the evidence, had already staked out a position to the effect that, while the previous (1997) recommendation for vitamin D (200 IU per day) was probably inadequate, the actual RDA was almost certainly below 1000 IU per day. Accordingly, when the statistical calculations produced a number that matched their own expectations, they may not have been inclined to question its derivation.
There is a generally held belief that science is objective, data-driven. And to a substantial extent that is so. But science and scientists are not identical. Scientists often have strongly held opinions and, like people in general, find ways to construe the evidence to support their beliefs. When those beliefs are wrong, science, as a field, ultimately abandons them. I am confident that this IOM error will be corrected sooner or later. This is partly because it is demonstrably erroneous, and partly because the related set of IOM recommendations for vitamin D has not elicited a consensus in the field of vitamin D research. If the Dietary Reference Intakes produced by the IOM are important, then it is important that they be right. I can only hope that not too much human damage will occur as we wait for the needed correction to happen.