Metabolic Syndrome and the Brain

Metabolic syndrome is an increasingly prevalent problem, not only in developed countries, but in developing countries as well.^{1, 2} The cluster of risk factors, which comprise metabolic syndrome, are usually thought to be strictly related to obesity.³ However, research shows that metabolic syndrome is correlated with severe cognitive dysfunction as well.^{4, 5} Risk factors for metabolic syndrome are defined as: raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity.^{6, 7}

So what exactly causes metabolic syndrome? Scientific literature suggests Westernization of diet is part of the problem.⁸ When we look at the brain impairment associated with metabolic syndrome, there are a variety of proposed causative mechanisms including impaired vascular reactivity, neuroinflammation, oxidative stress, and abnormal brain lipid metabolism.⁹

Model describing hypothesized brain vascular reactivity abnormalities resulting in brain impairments.

Interestingly, at least one study has shown that men are more affected, cognitively, than women.¹⁰ A comprehensive study on metabolic syndrome and the brain, found rats fed an omega-3 deficient diet exhibited memory deficits, which were further exacerbated by fructose intake.¹¹ This demonstrates that systemic inflammation and high sugar intake, specifically fructose, may be two possible precursors to cognitive decline, as well as obesity. It is also important to note the prevalence of a hypercaloric diet consisting of a high sugar intake and highly processed foods has coincided with an exponential rise in diabetes and metabolic syndrome, as well as cardiovascular diseases and cancer.¹² Nutrient intake directly correlates with brain volume as shown in the Nutrient Biomarker Pattern Score Diagram.¹³

Nutrient biomarker patterns and volumetric MRI (n = 42) Total cerebral brain volume (A, B) expressed as a % of total intracranial volume; white matter hyperintensity volume (C) includes periventricular and subcortical deep signals expressed as a % of total cerebral brain volume; x-axis represents the standardized score for NBP1-BCDE, NBP8–trans fat, and NBP5-marine ω-3 patterns.

Metabolic syndrome and cognitive dysfunction can further be explained via a 2011 study, which specifically showed how omega-3 deficiencies during pregnancy could affect multiple cognitive factors of new born offspring.¹⁴ Omega-3 deficiency was also shown to have effects on levels of brain-derived neurotrophic factor, an important gene in regulating stress, and in the biology of mood disorders.¹⁵ The image below shows how inadequate omega-3 intake can lead to cognitive and mood dysfunction.

Schematic representation for potential pathways by which n-3 dietary deficiency may enhance vulnerability to cognitive and mood disorders.

Omega-3 fatty acid deficiency, specifically an inadequate dietary intake of docosahexaenoic acid (DHA), is a recurring problem across these studies. DHA is vital to brain development, mood, and many other important physiological and cognitive functions.¹⁶ Other studies have shown brain tissue decline even early in the metabolic syndrome.¹⁷ High fructose consumption with an omega-3 deficient diet disrupts membrane homeostasis.¹⁸ Metabolic syndrome and brain dysfunction is even seen in adolescents, despite their much shorter lifespan.¹⁹ Researchers stated adolescents with metabolic syndrome show significantly lower arithmetic, spelling, attention, and mental flexibility and a trend for lower overall intelligence.

The takeaway: Westernization of diets, specifically over consumption of fructose, is closely linked with developing metabolic syndrome and its accompanying cognitive impairment. Deficiencies in anti-inflammatory omega-3 fatty acids have also been shown to correlate with metabolic syndrome and cognitive decline. A simple path to a healthier life is to adopt a Paleo Diet, which is generally extremely low in fructose, and high in omega-3 fatty acids. By giving your brain (and body) the right nutrients, you can thrive in all areas of life.

References

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2. Misra A, Bhardwaj S. Obesity and the metabolic syndrome in developing countries: focus on South Asians. Nestle Nutr Inst Workshop Ser. 2014;78:133-40.

3. Després JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006;444(7121):881-7.

4. Yaffe K, Weston AL, Blackwell T, Krueger KA. The metabolic syndrome and development of cognitive impairment among older women. Arch Neurol. 2009;66(3):324-8.

5. Taylor VH, Macqueen GM. Cognitive dysfunction associated with metabolic syndrome. Obes Rev. 2007;8(5):409-18.

6. Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640-5.

7. Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2009;2(5-6):231-7.

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10. Cavalieri M, Ropele S, Petrovic K, et al. Metabolic syndrome, brain magnetic resonance imaging, and cognition. Diabetes Care. 2010;33(12):2489-95.

11. Agrawal R, Gomez-pinilla F. ‘Metabolic syndrome’ in the brain: deficiency in omega-3 fatty acid exacerbates dysfunctions in insulin receptor signalling and cognition. J Physiol (Lond). 2012;590(Pt 10):2485-99.

12. Barnes JN, Joyner MJ. Sugar highs and lows: the impact of diet on cognitive function. J Physiol (Lond). 2012;590(Pt 12):2831.

13. Bowman GL, Silbert LC, Howieson D, et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology. 2012;78(4):241-9.

14. Bhatia HS, Agrawal R, Sharma S, Huo YX, Ying Z, Gomez-pinilla F. Omega-3 fatty acid deficiency during brain maturation reduces neuronal and behavioral plasticity in adulthood. PLoS ONE. 2011;6(12):e28451.

15. Available at: //www.ncbi.nlm.nih.gov/gene/627. Accessed July 8, 2014.

16. Horrocks LA, Yeo YK. Health benefits of docosahexaenoic acid (DHA). Pharmacol Res. 1999;40(3):211-25.

17. Sala M, De roos A, Van den berg A, et al. Microstructural brain tissue damage in metabolic syndrome. Diabetes Care. 2014;37(2):493-500.

18. Agrawal R, Gomez-pinilla F. ‘Metabolic syndrome’ in the brain: deficiency in omega-3 fatty acid exacerbates dysfunctions in insulin receptor signalling and cognition. J Physiol (Lond). 2012;590(Pt 10):2485-99.

19. Yau PL, Castro MG, Tagani A, Tsui WH, Convit A. Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics. 2012;130(4):e856-64.