Malocclusions and Urolithiasis in Evolutionary Medicine

1. Malocclusions and Urolithiasis in the Context of Evolutionary Medicine Giacinto Libertini giacinto.libertini@tin.it www.r-site.org/ageing www.programmed-aging.org

2. Preamble What is Evolutionary Medicine?

3. Evolutionary or Darwinian Medicine [1-6] comes into being in 1991 [1], but there are some known forerunners [7] (e.g. [8]) and others not generally cited as forerunners [9,10]. [1] Williams GC, Nesse RM (1991) The dawn of Darwinian medicine. Quart. Rev. Biol. 66, 1-22. [2] Nesse RM, Williams GC (1994) Why we get sick. New York (USA), Times Books. [3] Stearns SC (ed) (1999) Evolution in health and disease (1st ed.). Oxford (UK), Oxford University Press. [4] Trevathan WR, Smith EO, McKenna JJ (eds) (1999) Evolutionary Medicine. New York (USA), Oxford University Press. [5] Trevathan WR, Smith EO, McKenna JJ (eds) (2008) Evolutionary Medicine: new perspectives. New York (USA), Oxford University Press. [6] Stearns SC, Koella JC (eds) (2008) Evolution in health and disease (2nd ed.). Oxford (UK), Oxford University Press. [7] Trevathan WR, Smith EO, McKenna JJ (2008) Introduction and overview of Evolutionary Medicine. In: Trevathan WR, Smith EO, McKenna JJ (eds) Evolutionary Medicine: new perspectives. New York (USA), Oxford University Press. [8] Eaton SB, Shostak M, Konner M (1988) The paleolithic prescription: a program of diet & exercise and a design for living. New York (USA), Harper & Row. [9] Price WA (1939) Nutrition and Physical Degeneration. New York – London, Paul B. Hoeber. [10] Libertini G (1983) Ragionamenti Evoluzionistici. Naples (Italy), Società Editrice Napoletana; English Edition (2011): Evolutionary Arguments. Crownsville (USA), Azinet Press.

4. Evolutionary Medicine is not an Alternative Medicine (like homeopathy, iridology, ayurvedic medicine, naturopathy, traditional Chinese medicine, energy medicine, etc.) but a Medicine that is more thoroughly scientific In that it involves the concepts of Evolutionism. A medicine that ignored the principles of chemistry, for example, would be partially scientific. Similarly, a medicine that ignores the principles of evolution is partially scientific.

5. So the contrast is not between: Current Medicine Alternative Medicines but between: Evolutionary Medicine (which is a more thoroughly scientific medicine) Current Medicine (which in most cases ignores Evolutionism) However, the first practical question is immediate: Is this difference only a theoretical / verbal nicety? or Has this difference strong and significant implications for the structure of medical studies and for health organization?

6. Evolutionary Medicine involves many concepts and applicative consequences. Here, I develop a practical application of a simple concept, the “mismatch” [1,2], to the genesis of malocclusions and of urolithiasis. The concept of “mismatch” is simple but with huge implications: If a species is adapted to a certain range of conditions (including diet, environmental conditions, interrelations with other living beings, etc.), called for brevity “ecological niche”, any change in the ecological niche potentially is a source of disfunctions (diseases), because there is no adaptation to the new conditions. This is defined as "mismatch”. [1] Eaton SB, Shostak M, Konner M (1988) The paleolithic prescription: a program of diet & exercise and a design for living. New York (USA), Harper & Row. [2] Libertini G (2009) Prospects of a Longer Life Span beyond the Beneficial Effects of a Healthy Lifestyle, in: Bentely JV, Keller MA (eds) Handbook on Longevity: Genetics, Diet & Disease, New York (USA), Nova Science Publishers Inc.

7. Malocclusions and Urolithiasis in the Context of Evolutionary Medicine Step 1 - Epidemiological study of modern populations For Malocclusions: In USA: “Noticeable incisor irregularity occurs in the majority of all racial/ethnic groups, with only 35% of adults having well-aligned mandibular incisors. Irregularity is severe enough in 15% that both social acceptability and function could be affected, and major arch expansion or extraction of some teeth would be required for correction.” [1] In a study on Peruvian children: “The prevalence of malocclusions was 85.6%” [2] … [1] Proffit WR et al. (1998) Prevalence of malocclusion and orthodontic treatment need in the United States: estimates from the NHANES III survey. Int. J. Adult Orthodon. Orthognath. Surg. 13, 97-106. [2] Aliaga-Del Castillo A et al. (2011) [Malocclusions in children and adolescents from villages and native communities in the Ucayali Amazon region in Peru] [Article in Spanish] Rev. Peru Med. Exp. SaludPublica 28, 87-91.

8. Step 1 - (CONTINUED) … A study on Tanzanian children showed that 63.8 per cent of the subjects had at least one type of anomaly [1]. For Urolithiasis: “The overall probability of forming stones differs in various parts of the world: 1-5% in Asia, 5-9% in Europe, 13% in North America, 20% in Saudi Arabia.” [2] Among 20- to 74-old United States residents nephrolithiasis incidence increased from 3.8% in the period 1976-1980 to 5.2% in the period 1988-1994 [3]. “Recent data provide evidence that the incidence of nephrolithiasis in children is rising.” [4] “Pediatricurolithiasis has increased globally in the last few decades.” [5] … [1] Mtaya M et al. (2009) Prevalence of malocclusion and its relationship with socio-demographic factors, dental caries, and oral hygiene in 12- to 14-year-old Tanzanian schoolchildren. Eur. J. Orthod. 31, 467-76. [2] Ramello A et al. (2000) Epidemiology of nephrolithiasis. J. Nephrol. 13, S45-50. [3] Stamatelou KK et al. (2003) Time trends in reported prevalence of kidney stones in the United States: 1976-1994. Kidney Int. 63, 1817-23. [4]Sas DJ. (2011) An update on the changing epidemiology and metabolic risk factors in pediatric kidney stone disease. Clin. J. Am. Soc. Nephrol. 6, 2062-8. [5] Sharma AP, Filler G. (2010) Epidemiology of pediatricurolithiasis. Indian J. Urol. 26, 516-22.

9. Step 1 – (CONTINUED) … “There has been considerable increase in the incidence of idiopathic renal stone in Europe, North America, Australasia and Japan within the present century (Grossmann, 1938; Inada et al., 1958; Andersen, 1969; Fig. 4.1)” [1] [1] Trowell HC, Burkitt DP (eds) (1981). Western diseases, their emergence and prevention. Edward Arnold, USA.

10. Step 2 - Comparison between the frequency of a disease in modern populations and the frequency of the same disease in populations in primitive conditions For Malocclusions: “Although previous studies of primitive Eskimos have reported practically no malocclusion, 82 per cent of the children in this study had malocclusions.” [1] “It is a matter of great significance that the Eskimos who are living in isolated districts and on native foods have produced uniformly broad dental arches and typical Eskimo facial patterns. Even the first generation forsaking that diet and using the modern diet, presents large numbers of individuals with marked changes in facial and dental arch form” [2] “… from 25 to 75 per cent of individuals in various communities in the United States have a distinct irregularity in the development of the dental arches and facial form … In a study of 1,276 skulls of these ancient Peruvians, I did not find a single skull with significant deformity of the dental arches.” [2] (see fig. on the right) … Figure 78 from [2] • [1] Barry FW (1971) Malocclusion in the modern Alaskan Eskimo. Amer. J. Orthod. 60, 344-54. • [2] Price WA (1939) Nutrition and Physical Degeneration. New York – London, Paul B. Hoeber.

11. Step 2 – (CONTINUED) … Seminole Indians using native (left, fig. 24) and modernized (right, fig. 25) foods. “Note the change in facial and dental arch form in the children of this modernized group.” [1] … • [1]Price WA (1939) Nutrition and Physical Degeneration. New York – London, Paul B. Hoeber.

12. Step 2 – (CONTINUED) … “Another important source of information regarding the Aborigines of Australia was provided by a study of the skeletal material and skulls in the museums at Sydney and Canberra, particularly the former. I do not know the number of skulls that are available there for study, but it is very large. I examined many and found them remarkably uniform in design and quality. The dental arches were splendidly formed.” [1] “Note the marked difference in facial and dental arch form of the two Samoan primitives above and the two modernized below. The face bones are underdeveloped below causing a marked constriction of the arches with crowding of the teeth.” Comment to fig. 36 (on the right) from [1]. … • [1] Price WA (1939) Nutrition and Physical Degeneration. New York – London, Paul B. Hoeber.

13. Step 2 - (CONTINUED) … Price, in his irreproducible work, documented in many parts of the world (in people now completely modernized, but in 1939 divided into groups living in primitive conditions and others with more or less advanced degree of civilization) very different rates of tooth decay depending on the degree of diet modernization. In populations living with a natural diet, the set of teeth was well-formed, the bones of the face well developed, and the teeth practically free from caries. By contrast, in populations with modernized diets, the set of teeth was disordered, the face underdeveloped and tooth decay widespread, and all these alterations were proportional to the degree of diet modifications. [1] … Figures 17 (left) and 19 (right) from [1] • [1] Price WA (1939) Nutrition and Physical Degeneration. New York – London, Paul B. Hoeber.

14. Step 2 - (CONTINUED) ... For Urolithiasis: “Renal stone is rare among persons living in poor or primitive socio-economic circumstances and is very rare in African Bantu living under tribal conditions (Modlin, 1969)” [1] “To summarize, from being virtually unknown in historical times, renal stone has become significant as a common morbid condition in the affluent, westernized countries within the last 80 years whilst remaining rare in communities where the people live in primitive and poor conditions.” [1] Epidemiological data strongly contrast the possible hypothesis that the high frequencies of malocclusions and urolithiasis suffered by modern populations are caused by a recent (in evolutionary terms) relaxation of natural selection pressures. On the contrary, they indicate that these diseases are largely due to alterations of the ecological niche to which our species is adapted, that is presumable phenomena of mismatch. • [1] Trowell HC, Burkitt DP (eds) (1981). Western diseases, their emergence and prevention. Edward Arnold, USA.

15. Step 3 - Hypotheses on the possible changes in the ecological niche underlying the disease and on possible pathogenetical mechanisms Price, in his fundamental work [1], not surprisingly called Nutrition and Physical Degeneration, attributes the high frequency of malocclusions (and of other dental diseases) to changes in diet and lifestyle compared with the habits of primitive societies. A critical factor emphasized by Price is the amount of dietary vitamin D and of sun exposure for the formation of additional vitamin D. According to Price, an insufficient intake and absorption of dietary calcium in the early years of life determines, among other things, insufficient development of facial bones and an improper development of the set of teeth. Konner and Eaton [2] reported that prior to 1990 the recommended daily intake of vitamin D was 400 IU and that of calcium 800 mg. In 2010, this advice had become 1000 IU of vitamin D and 1000 mg of calcium. But the estimate for the ancestral population was over 4000 IU of vitamin D (also by sunlight) and 1500 mg of calcium. It is clear that with regard to ancestral conditions there is a strongly reduced intake of dietary calcium and a considerable deficiency of vitamin D, a poorly understood problem even in scientific circles. … [1] Price WA (1939) Nutrition and Physical Degeneration. New York – London, Paul B. Hoeber. [2] Konner M, Eaton SB (2010) Paleolithic Nutrition: Twenty-Five Years Later. Nutr. Clin. Pract. 25, 594-602.

16. Step 3 – (CONTINUED) … But if malocclusions are largely caused by reduced intake of dietary calcium and by reduced intake and production of vitamin D, these factors could seem to cause a reduced frequency of urolithiasis, a thing that is clearly contradicted by data from modernized population. However, it has been shown that urolithiasis frequency is inversely related to dietary calcium intake [1-3], even though supplemental calcium may increase the risk [2]. Dietary calcium reduces oxalate absorption and the urinary excretion of oxalate and this lowers the risk of kidney stones of calcium oxalate, the prevalent type of stones [1]. This “may be due to increased binding of oxalate by calcium in the gastrointestinal tract” [1]. Other factors correlated with a lower frequency of urolithiasis are potassium intake [1] and fluid intake [1]. The intake of fiber and plant foods reduces urinary calcium excretion and thus the frequency of the stones, while carbohydrate intake has the opposite effect [3]. A higher protein intake is associated with a moderate increase of urolithiasis risk [1]. … [1] Curhan GC et al. (1993) A Prospective Study of Dietary Calcium and Other Nutrients and the Risk of Symptomatic Kidney Stones. New Engl. J. Medic. 328, 833-8. [2] Curhan GC et al. (1997) Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann. Intern. Med. 126, 497-504. [3] Heller, HJ (1999) The role of calcium in the prevention of kidney stones. J. Am. Coll. Nutr. 18, 373S-378S.

17. Step 3 – (CONTINUED) It is essential to compare the ancestral diet with that of contemporary Western populations [1].In the table, the factors in the modern diet that increase urolithiasis risk are highlighted in pink, while those having the opposite effect are highlighted in green. It is not shown in the table the reduced intake of calcium in modern diets that is strongly correlated with urolithiasis frequency. [1] Konner M, Eaton SB (2010) Paleolithic Nutrition: Twenty-Five Years Later. Nutr. Clin. Pract. 25, 594-602.

18. Step 4 - Study of the mechanisms linking the alteration of the ecological niche to the pathogenesis of the disease For malocclusions The proper development of facial bones and set of teeth is optimal when the values ​​of dietary calcium and of vitamin D absorption and production are those to which our species is adapted. Modernized alimentation has severely altered these factors, and perhaps others that are more or less important to a correct development. The details of these alterations and the mechanisms by which the correct development is compromised require further information and explanations, but the correlation between alterations in diet and lifestyle and the correct development of facial bones and set of teeth are clear and well documented for a long time past [1]. [1] Price WA (1939) Nutrition and Physical Degeneration. New York – London, Paul B. Hoeber.

19. Step 4 – (CONTINUED) … For urolithiasis There is hypercalciuria in 95% of patients with nephrolithiasis[1]. The mechanism by which hypercalciuria causes an increased risk of renal stones is known [2]. There are foods that reduce calcium absorption, and therefore the urinary calcium - K, PO4, fiber, Alkali Load alias fruits and vegetables - and others that have the opposite effect – supplemental Ca, Na, Mg, Carbohydrates, Acid Load alias animal flesh - and the mechanisms that cause these effects are quite known [2]. But an increase in dietary calcium reduces oxalate absorption and oxalate excretion in the urine and thus reduces the frequency with which they form calcium oxalate stones, the most common type of calculations [3]. [1] Levy FL et al. (1995) Ambulatory evaluation of nephrolithiasis: an update of a 1980 protocol. Am. J. Med. 98, 50-9. [2] Heller, HJ (1999) The role of calcium in the prevention of kidney stones. J. Am. Coll. Nutr. 18, 373S-378S. [3] Curhan GC et al. (1993) A Prospective Study of Dietary Calcium and Other Nutrients and the Risk of Symptomatic Kidney Stones. New Engl. J. Medic. 328, 833-8.

20. Step 5 - Possible restoration of the normal, alias primeval, conditions or possible compensatory conditions • It is clear that Paleolithic diet and lifestyle are optimal to prevent malocclusions and urolithiasis, but it is also true that the return to ancestral conditions of life is not feasible. • More realistically, it is certainly useful to correct as much as possible those changes in diet and lifestyle that to a greater extent show to increase disease frequencies. • Available data suggest the following indications: • - to increase the intake of dietary calcium, potassium and vitamin D to the levels estimated for the Paleolithic ; • to increase the exposure to sunlight, so as to increase the production of vitamin D; • to increase the intake of foods and elements that reduce oxalate absorption and calcium absorption (and therefore urinary calcium: K, PO4, fiber, Alkali Load alias fruits and vegetables); • - to increase the intake of plain water; • to reduce the intake of the foods and elements that increase oxalate absorption and calcium absorption (and therefore urinary calcium: supplemental Ca, Na, Mg, Carbohydrates, Acid Load alias animal flesh).

21. Step 6 - Analysis of the results achieved and ideation and proposal of further improvements Afterwards, it will be indispensable to evaluate the results obtained with different types of diet more or less suited to these principles. Useful indications will be obtained from these results, which obviously in their application will be influenced by economic factors, dietary customs, and individual choices. At the same time, it is essential to continue the deepening of the study of ancestral conditions of life to which our body is better adapted. If these guidelines were not followed, the populations will gradually adapt to the new conditions of life with known evolutionary mechanisms, but it is good to point out that this choice is ethically unacceptable as it would result in countless cases of illness and death before, over many generations, a good adaptation will be reached.

22. First Objection Before applying these measures of prevention on a large scale, observation of controlled groups in order to confirm their validity is necessary. But this objection would be generated by a contradiction of current Medicine. In fact, if a new drug is proposed, we rightly expect a series of experiments, in several stages, before its use is authorized. Meanwhile, the NON-use of the drug is considered to be due and NOT subject to preventive experimentation. On the contrary, in the case of a new habit of life, alias a change of the ecological niche, the new habit is introduced and accepted WITHOUT any trial that demonstrates its safety. Now, If a new NOT tested habit of life is suspected of causing illness, the indication to stop this habit of life is rightful and proper. Why, before its suspension, should we demonstrate its harmfulness and the benefits resulting from its suspension?

23. Such an absurd principle has been used for decades to extend the use of smoke without that smokers were at least warned of the deadly risks they were running. Again a new habit (smoking) was introduced without any evidence that proved its safety and for decades it was claimed that its harm should be proved before taking action against it. After many scientific tests (while the slaughter continued)

24. Any change of the ecological niche to which a species is adapted must be considered potentially harmful until the contrary is proved. In the case of a new drug, this principle is observed! [Precautionary principle] But for other modifications of the ecological niche, no precaution is taken. It is presumed – irrationally and stupidly, because of non-scientific evaluations – that a modification must not be considered harmful until the experience proves the contrary! [Imprudence Principle]

25. The correct scientific logic would be to take steps against a change in the ecological niche on the sole grounds of the suspicion that this change is bad and BEFORE the sure demonstration in irreproachable scientific terms. Afterwards, the results in populations (or fractions of populations), which pursue - to a greater or lesser extent - the restoration of more physiological (alias natural) conditions must be compared both to confirm the expected results and for evaluating other possible measures. But one should not expect the results of test samples before applying the aforesaid preventive actions on a large scale.

26. Second Objection Malocclusions and urolithiasis should be attributed to the combination of environmental and genetic factors. This is a misleading way of describing the case. Certainly, when an individual is exposed to an ecological niche to which its genes are not adapted, in the diseases that are caused by the altered ecological niche, his genes, which are more or less resistant to the onset of diseases, come into play. But, we cannot and should not consider the genes that are less resistant to the diseases as pathological: they are entirely normal genes that in new conditions, to which the species is not adapted, have responses that are more or less effective against the onset of pathological changes. For example, our species is certainly not adapted to smoking. If, in smokers, some suffer respiratory failure, others chronic bronchitis and others cancer, it is not correct to say that those who develop these diseases have bad genes that somehow must be corrected, or for which it is necessary to develop opportune treatments. The logic says that we must avoid the alteration of the ecological niche and thus prevent the development of diseases that result from it. It should be noted that in some cases malocclusions or urolithiasis are actually due to genetic alterations. In these cases any preventive measure is not able to prevent the diseases. But, if we refer to data from the study of populations living under primitive conditions, the incidence of such cases is rare. Therefore, the attribution of responsibility to genetic factors should not be an excuse to diminish or avoid to address the most attention and efforts on prevention.

27. Malocclusions and urolithiasis involve significant costs and causes sufferings, reduced quality of life and even death. Current Medicine is directed to pursue means of correction that are increasingly sophisticated and refined. But the best goal would certainly be to minimize new cases of malocclusions and urolithiasis, reserving the cures to exceptional cases. This would limit the degradation of quality of life, a lot of suffering, and - last but something to be reckoned with - rising costs. This is possible with the correct application of trivial principles of Evolutionary Medicine. Conclusion

28. Conclusion Modern doctors, largely unaware even of the most basic principles of Evolutionism, do not know these possibilities. At the same time, evolutionary biologists are unaware of the extreme importance of these possibilities for a rational organization of a health system that should primarily prevent diseases. It is therefore essential the integration of the knowledge of Evolutionism in the active body of current Medicine, transforming it in Evolutionary Medicine.

29. Thanks for your attention This presentation is on my personal pages too: www.r-site.org/ageing (e-mail: giacinto.libertini@tin.it)