The Inuit Paradox Unravelled

The Inuit have often been cited in the past as support for a ketogenic diet. This is due to the incorrect belief that the Inuit have an unusually low risk of heart disease and that the reason for this might be due to ketosis (a high level of ketones in the bloodstream) caused by their high meat and fat diet. But does this paradox really exist?

The theory began in 1971 when Danish researchers, Hans Olaf Bang, Jørn Dyerberg, and Aase Brøndum, began a series of investigations into the health of the Greenland Inuit (1). Unfortunately they failed to study the outcome that their conclusions were centered upon, the true prevalence of coronary heart disease in Greenland. What they did investigate in the Inuit people were their blood lipid levels; their meals, consisting mainly of meat from whales, seals, seabirds and fish; and their causes of death. Cause of death statistics were gleaned from annual reports produced by the Chief Medical Officer of Greenland during the 1960s and 1970s which indicated low incidence of death from coronary artery disease and led the three researchers to speculate that marine fats from the meats the Inuit were eating were granting some sort of protection to coronary arteries.

Considering the remote areas where much of the population lived and died and where medical personnel were woefully lacking, investigations over the ensuing decades have questioned the validity of these medical reports (2).  A 2003 scientific paper from the National Institute of Public Health in Greenland produced autopsy studies and clinical observations that prove that heart disease was actually quite common among the Inuit, even in those of younger age (2). A recent 2014 review agreed, noting that more than 20% of the death certificates in the official records were completed with no examination of the body by a physician (3). Furthermore data accumulated over the past forty years shows that the incidence of coronary artery disease in the Inuit was not low at all but actually at a similar level to that of non-Inuit populations and that they also suffered from unusually high rates of cerebrovascular strokes. Even more illuminating is the life expectancy of the Inuit people of both Greenland and Canada which is ten years less than that of people living in more temperate latitudes and shows an overall mortality from all causes of twice that of non-Inuit populations (3,4). As if all this is not enough, there was the discovery of frozen Inuit mummies from thousands of years ago revealing advanced cardiovascular disease even in young people (5) and the fact that westernization of the Inuit diet, not generally a step towards better health, actually lowers their rates of heart disease (2). Finally, multiple studies over the last century examining Inuit people eating a traditional diet have found almost no occurrence of ketosis (6). The conclusion can only be that an Inuit Paradox does not exist.

Recently a startling piece of the Inuit puzzle has come to light that may explain why the state of ketosis is rare in Inuit people. Between 23,000 and 6,000 years ago a gene mutation of the CPT1a (carnitine palmitoyltransferase 1a) gene occurred in residents across the Arctic leaving them unable to develop ketosis (7). The CPT1a gene carries the instructions for making the enzyme that is essential for fatty acid oxidation, a process in which fats are broken down and converted into ketone bodies that can be used for energy.

It helps to understand this whole concept if you have an idea about what ketosis is. In brief, ketosis occurs when there is a very high level of ketone bodies in the bloodstream. Glucose is the preferred and, in some cases, essential energy source for human body cells. Glucose is easily obtained from carbohydrate sources such as fruits, vegetables and grains. Ketosis is a metabolic state that is the outcome of very low glucose availability due to starvation or a high fat diet with very low carbohydrate intake. Lack of glucose forces the body to turn to burning other macronutrients such as fat for energy. Fat is made up of fatty acids and many of our body tissues can use fatty acids directly for energy. Indeed humans evolved to be able to utilize fatty acids in order to survive periods of hardship such as drought when carbohydrates would be hard to find. However some body tissues cannot burn fatty acids directly and the brain is one of them. And so conversion of fatty acids into ketone bodies, a process that evolved to provide an emergency back-up fuel that would keep the brain alive during periods of food crisis, then comes into play to provide energy to the brain.

Why is ketosis so dangerous that it caused this major change in metabolism in this specific group of people? It is because severe ketosis can become ketoacidosis in which the accumulation of acidic compounds from the metabolism of fatty acids substantially lowers the pH of the blood (making it acidic) past the point where normal body mechanisms can bring it back into balance. This is a risky situation that can be fatal on its own but any added stress such as illness or injury, fairly common events in Inuit life especially in the past, can further lower the body’s pH and make death almost inevitable (15). Additionally, research in other populations shows that diets that produce ketosis are associated with higher rates of death from several specific causes and from all causes (18,19,20,21).

Now back to the prehistoric Inuit people who have populated the Arctic for millennia. In this harsh environment the growing season is very short and the cold dark winter can last for ten months of the year. It follows that access to plants for food (and a source of carbohydrates) was virtually impossible for most of the year. Only during the short summer could plant foods such as grasses, roots, seaweeds and berries be gathered. Accordingly the ancient Inuit were obliged to eat diets high in meat and fat most of the year, producing ketone bodies for energy and living at least part of the year in a state of ketosis (8). The process of evolution is always working away in the background towards its goal for all organisms, human or otherwise, and that goal is to survive long enough to procreate. The CPT1a gene mutation would at first have occurred randomly but it would result in lengthened lifespan for people with the mutation who were living under harsh arctic conditions. Very slowly, as genetic material was passed down through surviving generations, the CPT1a mutation became increasingly prevalent and eventually a very significant part of the genome of the Inuit. Today this mutation is present in 88% of Canadian Inuit, more than 80% of Greenland Inuit and about 68% of the people of northeast Siberia (7,9). It is a gene mutation that only appears in people of the Arctic.

People of the Arctic generally show few adverse effects of this gene alteration. However they do obtain their energy through an unusual variety of methods that employ fatty acids, ketone bodies and carbohydrates. The fatty acids derived from high fat foods are used directly as fuel in many body tissues. About 15 to 20% of CPT1a activity is retained allowing the slow production of ketone bodies, enough to fuel the brain and other tissues that cannot run on fats, but not in enough excess to cause ketosis (8,10). Glucose can be synthesized through the process of gluconeogenesis from amino acids released by the digestion of protein (11). Traditional Inuit consider the stomach contents of their prey a delicacy, offering an unexpected source of carbohydrate material (16). Lastly and perhaps most surprisingly, the ingestion of raw muscle meat and raw liver provides carbohydrate in the form of glycogen. Glycogen is the storage form of glucose for many organisms. In most meats the glycogen breaks down quickly after death of an animal and is not present at all after cooking (11,17). However in marine animals, creatures such as whales that have adapted to be able to withstand prolonged dives, glycogen breakdown after death is delayed due to their increased aerobic metabolism, allowing their glycogen to become a source of carbohydrate for those who end up eating them (12).

This mutation does have negative consequences. For instance it dramatically raises the risk of developing hypoglycemia while fasting. But it seems that over the centuries the Inuit have developed habits to combat this risk. Anecdotal evidence tells of their habit of always carrying snacks with them, especially during strenuous activity, to prevent the weakness, blurred vision, sweating and irritability that was common to them if they became hungry (14). These are classic symptoms of hypoglycemia. Also the increased risk of developing hypoglycemia created by the CPT1a mutation is considered the most probable explanation for the well-documented three-fold greater infant death rate in Arctic Canada as compared with the rest of the country (13).

Yet in spite of these destructive tendencies, natural selection effectively “judged” the CPT1a mutation as better suited for survival in the arctic environment. In other words, ketosis is perilous to life and avoiding ketosis confers a survival advantage for people eating a high-fat diet in a cold environment (7). In fact this particular mutation has been called the strongest “selective sweep” reported in humans; a case of the natural selection of a beneficial mutation raising it to a very high frequency in the affected population (7).

What does this fascinating story of natural selection in human beings all boil down to? First of all, it is astonishing that one small sector of the human population can been transformed to protect their survival in their unique environment. We can now understand that, not only is there no Inuit Paradox, it turns out that ketosis is not a possible path to cardiovascular health at all. Instead it is a threatening state strong enough to become the catalyst for significant evolutionary change, one that allowed the Inuit to eat the only diet available to them with fewer destructive consequences to their health.

 

SOURCES:

1 Bang HO, Dyerberg J, Nielsen AB. Plasma lipid and lipoprotein pattern in Greenlandic West-coast Eskimos. Lancet July 1971; 1(7710): 1143-1145.

2 Bjerregaard, P., Young, T.K., Hegele, R.A. Low incidence of cardiovascular disease among the Inuit – what is the evidence? Atherosclerosis. 2003 Feb; 166(2):351-357.

3 Fodor, J.G., Helis, E., Yazdekhasti, N., Vohnout, B. “Fishing” for the origins of the “Eskimos and heart disease” story: facts or wishful thinking? Can J Cardiol. 2014 Aug; 30(8):864-868.

4 https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=1310040301

5 Zimmerman, M.R. The paleopathology of the cardiovascular system. Tex Heart Inst J. 1993; 20(4):252-257.
The paleopathology of the cardiovascular system.

6 Heinbecker, P. Studies on the Metabolism of Eskimos. J. Biol. Chem. 1928;; 80 (2): 461–475.

7 Clemente, F.J, Cardona, A., Inchley, C.E., Peter, B.M., Jacobs, G., Pagani, L., Lawson, D.J., Antão, T., Vicente, M. et al. A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations. Am J Hum Genet. 2014 Nov 6; 95(5):584-589.

8 Greenberg, C.R., Dilling, L.A., Thompson, G.R., Seargeant, L.E., Haworth, J.C., Phillips, S., Chan, A., Vallance, H.D., Waters, P.J., Sinclair, G., Lillquist, Y., Wanders, R.J., Olpin, S.E. The paradox of the carnitine palmitoyltransferase type Ia P479L variant in Canadian Aboriginal populations. Mol Genet Metab. 2009 Apr;96(4):201-207.

9 Rajakumar, C., Ban, M.R., Cao, H., Young, T.K., Bjerregaard, P., Hegele, R.A. Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I. J Lipid Res. 2009 Jun; 50(6): 1223–1228.

10 Bennett, M.J., Santani, A.B., Carnitine Palmitoyltransferase 1A Deficiency. Gene Reviews; Editors – Adam, M.P., Ardinger,H.H., Pagon, R.A., et al., Seattle (WA): University of Washington, Seattle; 1993-2018.

11 Draper, H.H. The Aboriginal Eskimo Diet in Modern Perspective. American Anthropologist 1977; 79: 309-316.

12 Lockyer, C., Body composition of the sperm whale, Physeter cation, with special reference to the possible functions of fat depots. Journal of the Marine Research Institute. 1991; 12 (2).

13 https://www150.statcan.gc.ca/n1/pub/82-003-x/2017011/article/54886/tbl/tbl02-eng.htm

14 Klutschak, H. Overland to Starvation Cove. Trans. and Ed. William Barr. Canada: Univ. of Toronto Press, 1987.

15 Pankaj, S.,Kaur, H., Kaur, M. Clinical Profile of Diabetic Ketoacidosis: A Prospective Study in a Tertiary Care Hospital. J Clin Diagn Res. 2015 Jun; 9(6): OC01–OC04.

16 Rabinowitch, I.M. Clinical and Other Observations on Canadian Eskimos in the Eastern Arctic. Can Med Assoc J. 1936 May; 34(5): 487–501.

17 Pethick, D.W., Rowe, J.B., Tudor, G. Glycogen Metabolism and Meat Quality. Recent Advances in Animal Nutrition in Australia: July 199.5: 97-103.

18 Noto, H., Goto, A., Tsujimoto, T., Noda, M. Low-carbohydrate diets and all-cause mortality: a systematic review and meta-analysis of observational studies. PLoS One. 2013; 8(1):e55030.

19 Song, M., Fung, T.T., Hu, F.B., Willett, W.C., Longo, V., Chan, A.T., Giovannucci, E.L. Animal and plant protein intake and all-cause and cause-specific mortality: results from two prospective US cohort studies. JAMA Intern Med. 2016 Oct 1; 176(10): 1453–1463.

20 Ornish, D., Scherwitz, L.W., Billings, J.H., Brown, S.E., Gould, K.L., Merritt, T.A., Sparler, S., Armstrong, W.T., Ports, T.A., Kirkeeide, R.L., Hogeboom, C., Brand, R.J. Intensive lifestyle changes for reversal of coronary heart disease. JAMA. 1998 Dec 16;280(23):2001-2007.

21 Seidelmann, S.B., Claggett, B., Cheng, C., Henglin, M., Shah, A., Steffen, L.M., et al. Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis. Lancet. Sept. 2018; 3(9): PE419-E428.

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My name is Debra Harley (BScPhm) and I welcome you to my retirement project, this website. Over the course of a life many lessons are learned, altering deeply-rooted ideas and creating new passions.

2 Comments

  1. Marlene Clarke on January 25, 2019 at 10:37 am

    Very enlightening. Thank you.

  2. Susan Snelgrove on January 25, 2019 at 9:46 am

    Super interesting! I love u derstanding the science behind this topic.

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