Diet, Atherogenesis, and Dementia

  In 1961 the American Heart Association began recommending a low-fat diet on the premise that high saturated fat intake led to increased coronary artery disease. By 1980 this was endorsed by the USDA for general implementation, which is when the current unprecedented escalation of both diabetes and American obesity began.

Several nutrition experts now question if low-fat dietary guidelines resulted in carbohydrate sustitution, an observation supported by increased United States sugar consumption (Table I). Similarly, Americans also increased consumption of hydrogenated (“trans fats”) and subsequently plant-source polyunsaturated oils to replace the reduced animal fats (lard, tallow, etc).

Inspite of American success at reducing coronary artery disease-related mortality, the overall prevalence of atherogenesis-related diseases has continued at high levels internationally, and are now increasing in countries including China, India and Russia.

Similarlydespite public health successes locally like overall smoking reduction there is evidence of increased incidence of both Parkinson's disease and Alzheimer’s disease without comparable success in either secondary prevention or effective treatment for these common dementias.

  Alzheimer’s symptoms were formally described by Alois Alzheimer in 1906. Stephan Guyenet charted US sugar consumption using US Departments off Commerce and Agriculture data since the 1820’s, which revealed a striking increase until quite recently (Chart I). 

  On review of current sugar vs fat intakes (Chart II) we see that American sugar intake is much higher than Russia’s (126 vs. 20 g/d), whereas daily US fat intake is similar (66 vs. 69 g). Of interest, the US has a much higher Alzheimer’s disease-related death rate (45.6/100k) compared to Russia’s (2.2/100k). This led us to explore the relationship between diet and several Modern diseases, including dementia

  We found significant (p < 0.001) correlations (n=52 countries*) between estimated daily sugar intake, Alzheimer’s, & Parkinson’s-related death rates of different countries.

QUESTION: 

- Does excessive sugar intake correlate with atherogenesis

   Alzheimer’s

The stepwise multivariable regression analysis for Alzheimer’s yielded 3 variables in the best fit model: milk, stroke, and fish 

(F (3, 49) = 29.96, p < .001). The multivariate correlation was R = .827, predicting 65% of the variance in Alzheimer’s rate in the 53-country sample. The standardized beta coefficients for the significant predictor variables in order of entry were:

•Milk: .62 (t = 6.06, p < .001) •Stroke: -.26 (t = -2.52, p < .015) Fish: .18 (t = 2.03, p < .048)  Important questions for future investigation include (1) what would happen to the cognitive function in these patients if they decreased overall sugar (caloric?) intake significantly and (2) if they were able to do so successfully, would this reduce their risk of developing Alzheimer’s and/or Parkinson’s dementia(s).

Parkinson’s

The stepwise multivariable regression analysis for Parkinson’s yielded 4 variables in the best fit model: sugar, stroke, fish, and milk (F (4, 48) = 25.98, p < .001). The multivariate correlation was R = .827, predicting 65% of the variance of Parkinson’s rate in the 53-country sample. The standardized beta coefficients for the significant predictor variables in order of entry were:

•Sugar: .39 (t = 3.01, p < .004) •Stroke: -.22 (t = -1.96, p < .056) •Fish: .22 (t = 2.60, p < .012) •Milk: .30 (t = 2.54, p < .015)  

Important questions for future investigation include (1) what would happen to the cognitive function in these patients if they decreased overall sugar (caloric?) intake significantly and (2) if they were able to do so successfully, would this reduce their risk of developing Alzheimer’s and/or Parkinson’s dementia(s).

  The data were analyzed with a statistical software package (SPSS 25). Stepwise multiple regression analysis was used to sequentially identify the most parsimonious set of significant predictors for Parkinson’s and Alzheimer’s. Predictor variables were annual estimates of: sugar, milk, meat, fish, and alcohol consumption; obesity, stroke hypertension, cancer, and diabetes rates; tobacco use; obesity; and gross domestic product purchasing power parity (GDP-PPP) for 53 countries. Data came from on-line, publicly available World Health Organization (WHO), United Nations (UN), Global Change Data Lab, and World Bank sources.

  These results provide preliminary support that there is an important relationship between Parkinson's disease and dietary factors such as sugar, fish, and milk consumption. There is a likewise strong potential relationship between milk and fish intake for Alzheimer's disease. 

It is interesting that stroke was a significant negative predictor in both dementia types. The apparent “protective” effect of stroke (negative correlation) may be simply the prevention of dementia via earlier stroke-related death. The opposite may be true for what is happening with fish, where greater fish intake (a positive correlation) may correlate with longer life and thus higher probability of dementia. 

The impact of the other significant correlates for dementia risk from increased milk or sugar intake are less obvious. Does more milk correlate with increased carbohydrate/cereal intake? The potential relationship between dietary factors and dementia provides a clarion call for future prospective studies based on individual health data to better clarify how these factors might predispose us to either of these common dementias. 

Further investigation is needed. Specific examples for future studies include (1) examining the effects of significantly decreasing milk and/or sugar intake on cognitive function / extent of atherogenesis in participants with successful diet change as compared to those without, and (2) if maintaining these dietary changes long-term does reduce the risk of developing Alzheimer’s and/or Parkinson’s disease. 

  Claxson, Andrew W.D., Geoffrey E. Hawkes, David P. Richardson, et al. “Generation of Lipid Peroxidation Products in Culinary Oil and Fats During Episodes of Thermal Stressing: A High Field 1H NMR Study.” FEBS Letters355, no.1 (November 21, 1994): 81-90.

Cramptom, E. W., R. H. Common, E.T. Prichard, and Florence A. Farmer “Studies to Determine the Nature of the Damage to the Nutritive Value of Some Vegetable Oils from Heat Treatment: IV. Ethyl Esters of Heat Polymerized Linseed, Soybean and Sunflower Seed Oils.” Journal of Nutrition60, no.1 (September 10, 1956): 13-24.

Csallany, A. Saari, I. Han, D.W. Shoeman, and C. Chen. “4-Hydroxynonenal (HNE), a Toxic Aldehyde in French Fries from Fast Food Restaurants.” Poster presentation at the HNE Symposium, London, September 1-9, 2012.

Cummings, Richard Osborn. The American and His Food: A History of Food Habits in the United states. Chicago: The University of Chicago Press, 1940.

Damas, David. Arctic Migrants/Arctic Villagers: The Transformation of Inuit Settlement in the Central Arctic. Quebec: McGill-Queen’s Press, 2002.

Daniel, Carrie R., Amanda J. Cross, Corinna Koebnick, and Rashmi Sinha. “Trends in Meat Consumption in the USA.” Public Health Nutrition 14 no. 4(2011): 575-583.

DISC Collaborative Research Group. “Dietary Intervention Study in Children (DISC) with Elevated Low Density Lipoprotein Cholesterol: Design and Baseline Characteristics.” Annals of Epidemiology 3, no. 4 (July 1993): 393-402.

Enig, Mary G. Trans Fatty Acids in the Food Supply: A Comprehensive Report Covering 60 Years of Research, 2nd Edition. Silver Spring, MD: EnigAssociates, 1995.

Esterbauer, Hermann, Rudolf Jörg Schaur, and Helmward Zollner. “Chemistry and Biochemistry of 4-Hydroxynonenal, Malonaldehyde and Related Aldehydes.” Free Radical Biology & Medicine 11, no.1 (1991): 81-128.

Feron, V.J., H. P. Til, Flora de Vrijer, et al. “Aldehydes: Occurrence, Carcinogenic Potential, Mechanism of Action and Risk Assessment.” Mutation Research 259, no. 3-4 (March-April 1991): 363-385.

Keys, Ancel, Alessandro Menotti, MaritiJ. Karvonen, et. al. “The Diet and 15-year Death Rate in the Seven Countries Study.” American Journal of Epidemiology 124, no. 6 (December 1986): 903-915.

Keys, Ancel, Alessandro Menotti, Christos Aravanis, et al. “The Seven Countries Study: 2,289 Deaths in 15 Years.” Preventive Medicine 13, no. 2 (March 1984): 141-154.

Krauss, Ronald M. “Dietary and Genetic Probes of Atherogenic Dyslipidemia.” Arteriosclerosis, Thrombosis, and Vascular Biology 25, no. 11 *November 2005): 2265-2275.

Krauss, Ronald M., Patricia J. Blanche, Robin S. Rawlings, Harriett S. Fernstrom, and Paul T. Williams. “Separate Effects of Reduced Carbohydrate Intake and Weight Loss on Atherogenic Dyslipidemia.” American Journal of Clinical Nutrition 83, no. 5 (May 2006): 1025-1031. 

Krauss, Ronald M., and Darlene M. Dreon. “Low-density-lipoprotein Sibclassesand Response to a Low-fat Diet in Healthy Men.” American Journal of Clinical Nutrition 62, no. 2 suppl. (August 1995): 478S-487S.

Menotti, Alessandro, Daan Kromhout, Henry Blackburn, FlaminioFidanza, Ratko Buzina, and Aulikki Nissinen. “Food Intake Patterns and 25-Year Mortality from Coronary Heart Disease: Cross-Cultural Correlation in the Seven Countries Study.” European Journal of Epidemiology 15, no. 6 (1999): 507-515. 

Multiple Risk Factor Intervention Trial Research Group. “Multiple Risk Factor Intervention Trial: Risk Factor Changes and Mortality Results.” Journal of American Medicine 248, no. 12 (September 24, 1982): 1465-1477. 

“A Reorientation of Obestiy.” New England Journal of Medicine 248, no 23 (June 4, 1953): 959-964.

“Treatment of Obesity: Developments of the Past 150 Years.” American Journal of Digestive Disease 21, no. 3 (March 1954): 65-69. 

Taubes, Gary. “The Soft Science of Dietary Fat”Science 291, no. 5513 (March 2001): 2536-2545

Good Calories, Bad Calories: Fats, Carbs, and the Controversial Science of Diet and Health. New York: Alfred A. Knopf, 2007. 

“The Science of Obesity: What Do We Really Know about What Makes Us Fat? An Essay by Taubes.” British Medical Journal 346 (April 16, 2013).

Volek, Jeff S., Kevin D. Ballard, Ricardo Silvestre, et al. “Effects of Dietary Carbohydrate RestricationVersus Low-Fat Diet on Flow Mediated Dilation” Metabolism58, no. 12 (December 2009): 1769-1777

Volek, Jeff S., Stephen D. Phinney, Cassandra E. Forsythe, et al. “Carbohydrate Restriction Has a More Favorable Impact on the Metabolic Syndrome than a Low FatDiet.” Lipids 44, no 4 (April 2009): 297-309.

Volek, Jeff S., Matthew Sharman, Ana Gomez, et al. “Comparison of Energy-Restricted Very Low-Carbohydrate and Low-Fat Diets on Weight Loss and Body Composition in Over-weight Men and Women '' Nutrition & Metabolism 1, no. 13 (2004):1-32

Westman, Eric C. “Rethinking Dietary Saturated Fat.” Food Technology 63, no. 2 (2009): 30

Westman, Eric C., Richard D. Feinman, John C. Mavropoulos, et al. “Low-Carbohydrate Nutrition and Metabolism.” American Journal of Clinical Nutrition 86, no. 2 (August 2007): 276-284.

Westman, Eric C., John C. Mavropoulos, William S. Yancy, and Jeff S. Volek. “A Review of Low-Carbohydrate Ketogenic Diets.” Current Atherosclerosis Reports 5, no. 6 (November 2003): 476-483.

Westman, Eric C., Jeff S. Volek, and Richard D. Feinman. “Carbohydrate Restriction Is Effective in Improving A therohenicDyslipidemia even in the Absence of Weight Loss.” American Journal of Clinical Nutrition 84, no. 6 (December 2006): 1549.

•http://www.alz.org/research/science/major_milestones_in_alzheimers.asp#first •http://onlinestatbook.com/2/case_studies/sugar.html •Ferdman, Roberto A. “Where people around the world eat the most sugar and fat.” The Washington Post. WP Company, 05 Feb. 2015. Web. July 2017. •“Alzheimers/Dementia Death Rate By Country.” World Life Expectancy. World Health Organization, n.d. Web. July 2017. •“Parkinson’s Disease Death Rate By Country.” World Life Expectancy. World Health Organization, n.d. Web. July 2017.  •Lakhan, S. and Kirchgessner, A. (2013) The emerging role of dietary fructose in obesity and cognitive decline, Nutrition Journal, 12:114. 

*Countries included in this review, listed in order of greatest to the least daily sugar intake include: United States, Germany, Netherlands, Ireland, Australia, Belgium, United Kingdom, Mexico, Finland, Canada, Austria, Sweden, Norway, New Zealand, Saudi Arabia, Switzerland, Denmark, Argentina, Czech Republic, Spain, France, Slovakia, Chile, Italy, Poland, Japan, Greece, Peru, Portugal, Hungary, Brazil, United Arab Emirates, South Africa, Bulgaria, Columbia, Turkey, Malaysia, Singapore, Romania, South Korea, Venezuela, Thailand, Vietnam, Philippines, Russia, Egypt, Morocco, Ukraine, China, Indonesia, Israel, and India.