I commend the BMJ on publishing more debate on dietary advisories in ‘Are some diets “mass murder”?’ by Richard Smith. He has penned papers such as ‘Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies’ which is relevant to diet related disease. More and more medication is prescribed to treat the risk markers (not causes) of hypertension, dyslipidaemia and hyperglycaemia for diabetes, liver, and cardiovascular (CV)and neurodegenerative diseases, and cancer. Nutraceuticals, vitamins as well as medication is sold to manage obesity. There is less and less emphasis on real, high nutrient food as being preventative of, and probably able to ameliorate, much obesity related metabolic syndrome (MetS).
However, although Smith’s overall ideas, and those of the popular and scientific authors he cites probably lie in the correct direction, none acknowledges some very basic and highly likely scientific theory about diet in humans.
It would seem eminently sensible, and remiss not to start, to look at human evolution and most importantly to review the metabolic oddities that we find in large brained human mammals1.
Evidence that humans have evolved some intriguing interrelated pathways in energy metabolism2 and micronutrient nutrition3 4, including fat turnover and storage5, should not come as surprise to scientists. Furthermore unique human brain neurotransmitter biology6 relates to strong behavioural drives for finding or producing energy dense food, and in fact for ‘perseveration’ in many human endeavours. These factors together should indicate that reliance on studies of small nocturnal, short-lived, rodents (lab rats and mice) which are bred or engineered to live outside their natural habitat, will not yield appropriate science on diets for humans.
Once humans got to the stage of devising and building technology that changed their physical, chemical and dietary environment, development tended to proceed under pressure from technology-commodity driven industry. Evidence again indicates that once humans started farming, approximately 10,000 years ago7, energy dense, preserveable, rather than nutrient dense, food was produced and traded, and human health and robustness declined8 9.
As Smith’s articles allude to, the current food and drug industry has picked up parts of medical science that it can profit from and dissuaded researchers from pursuing solid, hypothesis driven biological science, using basic principles, such as Bradford Hill’s criteria10 11.
Ironically, the science on appropriate food for humans has largely been undertaken, albeit accidentally, in studies where the right questions were not asked and results poorly interpreted; we just have to apply real scientific hypothesis and start from the beginning of this science – human evolution - which we can now do12 13. Studies on human diet and health can no longer be single-item, reductionist, randomised controlled trials (RCT) alone.
Smith has critiqued a meta-analyses of RCT type studies, which commonly do not produce clear results, when the questions of what was studied, and how, were not appropriate. He has spent much time in the past, when he was the BMJ editor involved in investigating a single researcher in India, who was at least investigating a difficult area (multi-nutrient food effects on cardiovascular health) in difficult conditions before the correct tools were developed, and at worst fabricating data.
In fact, a more robust meta-analysis of high nutrient, low toxicity diets 14, and studies of the traditional Mediterranean diet 15-30, along with systems modelling that are starting to be used in energetics and epidemiology of nutrition31 show that whole food diets will likely lead to improved health at the population level. Further evolutionary and epidemiological data collection, together with prospective clinical and community studies, and human physiological studies all augmented with sophisticated mathematical systems modelling, is urgently required.
Oddly, the free internet has now become a repository of extremes – well thought out science that the major journals rarely publish, and crackpot opinion. These are what the public read – and many people can see the value of pre-agricultural forager type-diets for conferring health. Increased efforts are being made by some to move to ‘paleo diets’.
However, high nutrient, uncontaminated, whole food based diets will likely suffice if it is the nutrient density that is important, and this is the scientific debate that public health researchers and policy makers need to air in high profile journals, without industrial interference.
1. Leonard WR, Snodgrass JJ, Robertson ML. Effects of Brain Evolution on Human Nutrition and Metabolism. Annu. Rev. Nutr. 2007;27(1):311-27.
2. Zhang Q, Pi J, Woods CG, Andersen ME. A systems biology perspective on Nrf2-mediated antioxidant response. Toxicol. Appl. Pharmacol. 2010;244(1):84-97.
3. Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem. Sci. 2014;39(4):199-218.
4. Dinkova-Kostova AT, Kostov RV. Glucosinolates and isothiocyanates in health and disease. Trends Mol. Med. 2012;18(6):337-47.
5. Cunnane SC, Crawford MA. Survival of the fattest: fat babies were the key to evolution of the large human brain. Comp. Biochem. Physiol. 2003;136(1):17-26.
6. Shumay E, Fowler JS, Volkow ND. Genomic features of the human dopamine transporter gene and its potential epigenetic states: Implications for phenotypic diversity. PLoS ONE 2010;5(6):1-17.
7. O'Keefe JH, Jr., Cordain L, O'Keefe JH, Jr., Cordain L. Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer. Mayo Clin. Proc. 2004;79(1):101-8.
8. Mummert A, Esche E, Robinson J, Armelagos GJ. Stature and robusticity during the agricultural transition: Evidence from the bioarchaeological record. Econ. Hum. Biol. 2011;9(3):284-301.
9. David AR, Zimmerman MR. Cancer: an old disease, a new disease or something in between? Nat. Rev. Cancer 2010;10(10):728-33.
10. Hill AB. The Environment and Disease: Association or Causation? Proc. R. Soc. Med. 1965;58:295-300.
11. Phillips CV, Goodman KJ. Causal criteria and counterfactuals; nothing more (or less) than scientific common sense. Emerg Themes Epidemiol 2006;3:5.
12. McGill A-T. Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption. Arch. Public Health 2014;72(1):31.
13. McGill A-T. Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption. Arch. Public Health 2014;72(1):30.
14. Barański M, Średnicka-Tober D, Volakakis N, Seal C, Sanderson R, Stewart GB, et al. Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses. Br. J. Nutr. 2014;112(05):794-811.
15. Grosso G, Pajak A, Mistretta A, Marventano S, Raciti T, Buscemi S, et al. Protective role of the Mediterranean diet on several cardiovascular risk factors: evidence from Sicily, southern Italy. Nutrition, metabolism, and cardiovascular diseases : NMCD 2014;24(4):370-7.
16. Busko M. Mediterranean Diet Reverses Metabolic Syndrome in PREDIMED. Medscape.com 2014;October (14):http://www.medscape.com/viewarticle/833218_print.
17. Estruch R, Ros E, Salas-Salvadó J, Covas M-I, Corella D, Arós F, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N. Engl. J. Med. 2013;DOI: 10.1056/NEJMoa1200303.
18. Issa C, Darmon N, Salameh P, Maillot M, Batal M, Lairon D. A Mediterranean diet pattern with low consumption of liquid sweets and refined cereals is negatively associated with adiposity in adults from rural Lebanon. Int. J. Obes. 2011;35(2):251-8.
19. Tangney CC, Kwasny MJ, Li H, Wilson RS, Evans DA, Morris MC. Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am. J. Clin. Nutr. 2010;93(3):601-7.
20. Elhayany A, Lustman A, Abel R, Attal-Singer J, Vinker S. A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study. Diabetes Obes. Metab. 2010;12(3):204-09.
21. Esposito K, Maiorino M, Ciotola M, Palo CD, Scognamiglio P, Gicchino M, et al. Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients With Newly Diagnosed Type 2 Diabetes - A Randomized Trial. Ann. Intern. Med. 2009;151:306-14.
22. Caudwell P, Hopkins M, King NA, Stubbs RJ, Blundell JE. Exercise alone is not enough: weight loss also needs a healthy (Mediterranean) diet? Public Health Nutr. 2009;12(9A):1663-6.
23. Mackenbach JP. The Mediterranean diet story illustrates that "why" questions are as important as "how" questions in disease explanation. J. Clin. Epidemiol. 2007;60(2):105-9.
24. de Lorgeril M, Salen P. Modified cretan Mediterranean diet in the prevention of coronary heart disease and cancer: An update. World Rev. Nutr. Diet. 2007;97:1-32.
25. Tapsell LC, Hemphill I, Cobiac L, Patch CS, Sullivan DR, Fenech M, et al. Health benefits of herbs and spices: the past, the present, the future. Med. J. Aust. 2006;185(4 Suppl):S4-24.
26. Gerber M. Biofactors in the Mediterranean diet. Clin. Chem. Lab. Med. 2003;41(8):999-1004.
27. de Lorgeril M, Salen P, Martin JL, Monjaud I, Boucher P, Mamelle N. Mediterranean dietary pattern in a randomized trial: prolonged survival and possible reduced cancer rate.[see comment]. Arch. Intern. Med. 1998;158(11):1181-7.
28. De Lorgeril M, Salen P, Martin JL, Mamelle N, Monjaud I, Touboul P, et al. Effect of a mediterranean type of diet on the rate of cardiovascular complications in patients with coronary artery disease. Insights into the cardioprotective effect of certain nutriments.[see comment]. J. Am. Coll. Cardiol. 1996;28(5):1103-8.
29. Ulijaszek SJ. Human dietary change. Philos. Trans. R. Soc. Lond. B Biol. Sci. 1991;334(1270):271-8; discussion 78-9.
30. Dunn FL. Epidemiological Factors: Health and Disease in Hunter-Gatherers. In: Lee R, DeVore I, editors. Man the Hunter. Chicago Aldine, 1968.
31. Leonard WR, Ulijaszek SJ. Energetics and evolution: an emerging research domain. Am. J. Hum. Biol. 2002;14(5):547-50.
Competing interests:
No competing interests
05 January 2015
Anne-Thea McGill
GP and Clinical Researcher
University of Auckland
School of Population Health | Private Bag 92019, Auckland, 1142 | New Zealand
Rapid Response:
Dear Editor
I commend the BMJ on publishing more debate on dietary advisories in ‘Are some diets “mass murder”?’ by Richard Smith. He has penned papers such as ‘Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies’ which is relevant to diet related disease. More and more medication is prescribed to treat the risk markers (not causes) of hypertension, dyslipidaemia and hyperglycaemia for diabetes, liver, and cardiovascular (CV)and neurodegenerative diseases, and cancer. Nutraceuticals, vitamins as well as medication is sold to manage obesity. There is less and less emphasis on real, high nutrient food as being preventative of, and probably able to ameliorate, much obesity related metabolic syndrome (MetS).
However, although Smith’s overall ideas, and those of the popular and scientific authors he cites probably lie in the correct direction, none acknowledges some very basic and highly likely scientific theory about diet in humans.
It would seem eminently sensible, and remiss not to start, to look at human evolution and most importantly to review the metabolic oddities that we find in large brained human mammals1.
Evidence that humans have evolved some intriguing interrelated pathways in energy metabolism2 and micronutrient nutrition3 4, including fat turnover and storage5, should not come as surprise to scientists. Furthermore unique human brain neurotransmitter biology6 relates to strong behavioural drives for finding or producing energy dense food, and in fact for ‘perseveration’ in many human endeavours. These factors together should indicate that reliance on studies of small nocturnal, short-lived, rodents (lab rats and mice) which are bred or engineered to live outside their natural habitat, will not yield appropriate science on diets for humans.
Once humans got to the stage of devising and building technology that changed their physical, chemical and dietary environment, development tended to proceed under pressure from technology-commodity driven industry. Evidence again indicates that once humans started farming, approximately 10,000 years ago7, energy dense, preserveable, rather than nutrient dense, food was produced and traded, and human health and robustness declined8 9.
As Smith’s articles allude to, the current food and drug industry has picked up parts of medical science that it can profit from and dissuaded researchers from pursuing solid, hypothesis driven biological science, using basic principles, such as Bradford Hill’s criteria10 11.
Ironically, the science on appropriate food for humans has largely been undertaken, albeit accidentally, in studies where the right questions were not asked and results poorly interpreted; we just have to apply real scientific hypothesis and start from the beginning of this science – human evolution - which we can now do12 13. Studies on human diet and health can no longer be single-item, reductionist, randomised controlled trials (RCT) alone.
Smith has critiqued a meta-analyses of RCT type studies, which commonly do not produce clear results, when the questions of what was studied, and how, were not appropriate. He has spent much time in the past, when he was the BMJ editor involved in investigating a single researcher in India, who was at least investigating a difficult area (multi-nutrient food effects on cardiovascular health) in difficult conditions before the correct tools were developed, and at worst fabricating data.
In fact, a more robust meta-analysis of high nutrient, low toxicity diets 14, and studies of the traditional Mediterranean diet 15-30, along with systems modelling that are starting to be used in energetics and epidemiology of nutrition31 show that whole food diets will likely lead to improved health at the population level. Further evolutionary and epidemiological data collection, together with prospective clinical and community studies, and human physiological studies all augmented with sophisticated mathematical systems modelling, is urgently required.
Oddly, the free internet has now become a repository of extremes – well thought out science that the major journals rarely publish, and crackpot opinion. These are what the public read – and many people can see the value of pre-agricultural forager type-diets for conferring health. Increased efforts are being made by some to move to ‘paleo diets’.
However, high nutrient, uncontaminated, whole food based diets will likely suffice if it is the nutrient density that is important, and this is the scientific debate that public health researchers and policy makers need to air in high profile journals, without industrial interference.
1. Leonard WR, Snodgrass JJ, Robertson ML. Effects of Brain Evolution on Human Nutrition and Metabolism. Annu. Rev. Nutr. 2007;27(1):311-27.
2. Zhang Q, Pi J, Woods CG, Andersen ME. A systems biology perspective on Nrf2-mediated antioxidant response. Toxicol. Appl. Pharmacol. 2010;244(1):84-97.
3. Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem. Sci. 2014;39(4):199-218.
4. Dinkova-Kostova AT, Kostov RV. Glucosinolates and isothiocyanates in health and disease. Trends Mol. Med. 2012;18(6):337-47.
5. Cunnane SC, Crawford MA. Survival of the fattest: fat babies were the key to evolution of the large human brain. Comp. Biochem. Physiol. 2003;136(1):17-26.
6. Shumay E, Fowler JS, Volkow ND. Genomic features of the human dopamine transporter gene and its potential epigenetic states: Implications for phenotypic diversity. PLoS ONE 2010;5(6):1-17.
7. O'Keefe JH, Jr., Cordain L, O'Keefe JH, Jr., Cordain L. Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer. Mayo Clin. Proc. 2004;79(1):101-8.
8. Mummert A, Esche E, Robinson J, Armelagos GJ. Stature and robusticity during the agricultural transition: Evidence from the bioarchaeological record. Econ. Hum. Biol. 2011;9(3):284-301.
9. David AR, Zimmerman MR. Cancer: an old disease, a new disease or something in between? Nat. Rev. Cancer 2010;10(10):728-33.
10. Hill AB. The Environment and Disease: Association or Causation? Proc. R. Soc. Med. 1965;58:295-300.
11. Phillips CV, Goodman KJ. Causal criteria and counterfactuals; nothing more (or less) than scientific common sense. Emerg Themes Epidemiol 2006;3:5.
12. McGill A-T. Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption. Arch. Public Health 2014;72(1):31.
13. McGill A-T. Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption. Arch. Public Health 2014;72(1):30.
14. Barański M, Średnicka-Tober D, Volakakis N, Seal C, Sanderson R, Stewart GB, et al. Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses. Br. J. Nutr. 2014;112(05):794-811.
15. Grosso G, Pajak A, Mistretta A, Marventano S, Raciti T, Buscemi S, et al. Protective role of the Mediterranean diet on several cardiovascular risk factors: evidence from Sicily, southern Italy. Nutrition, metabolism, and cardiovascular diseases : NMCD 2014;24(4):370-7.
16. Busko M. Mediterranean Diet Reverses Metabolic Syndrome in PREDIMED. Medscape.com 2014;October (14):http://www.medscape.com/viewarticle/833218_print.
17. Estruch R, Ros E, Salas-Salvadó J, Covas M-I, Corella D, Arós F, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N. Engl. J. Med. 2013;DOI: 10.1056/NEJMoa1200303.
18. Issa C, Darmon N, Salameh P, Maillot M, Batal M, Lairon D. A Mediterranean diet pattern with low consumption of liquid sweets and refined cereals is negatively associated with adiposity in adults from rural Lebanon. Int. J. Obes. 2011;35(2):251-8.
19. Tangney CC, Kwasny MJ, Li H, Wilson RS, Evans DA, Morris MC. Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am. J. Clin. Nutr. 2010;93(3):601-7.
20. Elhayany A, Lustman A, Abel R, Attal-Singer J, Vinker S. A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study. Diabetes Obes. Metab. 2010;12(3):204-09.
21. Esposito K, Maiorino M, Ciotola M, Palo CD, Scognamiglio P, Gicchino M, et al. Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients With Newly Diagnosed Type 2 Diabetes - A Randomized Trial. Ann. Intern. Med. 2009;151:306-14.
22. Caudwell P, Hopkins M, King NA, Stubbs RJ, Blundell JE. Exercise alone is not enough: weight loss also needs a healthy (Mediterranean) diet? Public Health Nutr. 2009;12(9A):1663-6.
23. Mackenbach JP. The Mediterranean diet story illustrates that "why" questions are as important as "how" questions in disease explanation. J. Clin. Epidemiol. 2007;60(2):105-9.
24. de Lorgeril M, Salen P. Modified cretan Mediterranean diet in the prevention of coronary heart disease and cancer: An update. World Rev. Nutr. Diet. 2007;97:1-32.
25. Tapsell LC, Hemphill I, Cobiac L, Patch CS, Sullivan DR, Fenech M, et al. Health benefits of herbs and spices: the past, the present, the future. Med. J. Aust. 2006;185(4 Suppl):S4-24.
26. Gerber M. Biofactors in the Mediterranean diet. Clin. Chem. Lab. Med. 2003;41(8):999-1004.
27. de Lorgeril M, Salen P, Martin JL, Monjaud I, Boucher P, Mamelle N. Mediterranean dietary pattern in a randomized trial: prolonged survival and possible reduced cancer rate.[see comment]. Arch. Intern. Med. 1998;158(11):1181-7.
28. De Lorgeril M, Salen P, Martin JL, Mamelle N, Monjaud I, Touboul P, et al. Effect of a mediterranean type of diet on the rate of cardiovascular complications in patients with coronary artery disease. Insights into the cardioprotective effect of certain nutriments.[see comment]. J. Am. Coll. Cardiol. 1996;28(5):1103-8.
29. Ulijaszek SJ. Human dietary change. Philos. Trans. R. Soc. Lond. B Biol. Sci. 1991;334(1270):271-8; discussion 78-9.
30. Dunn FL. Epidemiological Factors: Health and Disease in Hunter-Gatherers. In: Lee R, DeVore I, editors. Man the Hunter. Chicago Aldine, 1968.
31. Leonard WR, Ulijaszek SJ. Energetics and evolution: an emerging research domain. Am. J. Hum. Biol. 2002;14(5):547-50.
Competing interests: No competing interests