The 4 Horsemen of Disease and the Connection to Metabolic Health

For our January series on metabolic health and its impact on the brain and other diseases, here we’ll introduce you to the interplay of the “Four Horsemen” and how metabolic health is involved. 

In the pursuit of a long and healthy life, managing the risk of diseases takes center stage, and among the most concerning are the “Four Horsemen of Disease,” a term coined by world-renowned longevity expert Peter Attia, M.D.1  These Four Horsemen are  (1) metabolic disorder, (2) cancer, (3) cardiovascular disease, and (4) neurodegenerative disease, which are chronic, highly fatal (if left unmanaged), and kill the vast majority of people in developed nations.   

All Four Horsemen share a commonality:  chronic inflammation, which is persistent and low-grade immune response in the body that can contribute to the development and progression of these ailments.2  Understanding, assessing, and strategically reducing the risks associated with chronic inflammation become pivotal focal points for proactive health measures.  Read on for the Four Horseman of Disease and their risk factors.  

The 4 Horsemen of Disease and the Connection to Metabolic Health

 1. Metabolic Syndrome and Disorder 

Metabolic health has far-reaching consequences on many diseases, with particular impact to the three other Horsemen.  Often, you’ll hear of metabolic health problems described as “metabolic syndrome,” which is a combination of three or more of the following conditions:3,4 

  • high insulin,  
  • hyperglycemia (high sugar in the blood),  
  • hypertension,  
  • low high-density lipoprotein (HDL),  
  • high very low-density lipoprotein (VLDL), and  
  • abdominal obesity.  

Chances are, you’ve heard your doctor mention a few of these as important indicators for your health when you get your annual exam.  Factors that contribute to these are excess weight, general obesity, sedentary habits, and genetic predisposition, which can ultimately lead to insulin resistance and type 2 diabetes, the most well-known metabolic disorder.  Insulin resistance can harm small blood vessels, making a person more likely to have problems with how their blood vessels work, increased pressure in the blood vessels, and inflammation in the vessel walls.  This damage to the vessels can disrupt the body's balance and lead to diseases like cardiovascular disease and high blood pressure.  For those who have type 2 diabetes, the risk of a neurodegenerative disease, like Alzheimer’s disease, can be as high as 65%. 5  And metabolic syndrome is a key driver for chronic inflammation, which scientists believe is caused by continuous overload of fat cells in the body by un-used calories, which leads to continuous activation of the immune system that can cause long-term damage to many parts of the body. 

So, it’s no surprise that metabolic health is key to brain health and overall health! 

2. Cancer 

Cancer is a leading cause of death, responsible for 1 in 6 fatalities.7  It may be surprising, but only a small fraction (5%-10%) of cancer cases result from pure DNA mutations.8  The majority of cancers are influenced by external factors such as chronic infections, dietary choices, obesity, exposure to pollutants, smoking, and autoimmune conditions.  Long-term chronic inflammation triggers the activation of genes that promote cancer growth and suppresses genes that normally prevent it.  This leads to genetic instability and the formation of tumors by encouraging the uncontrolled growth and survival of cancer cells.8  Cancer cells also have an altered metabolic state, where the pathways of glucose (sugar) and fatty acids are affected.9  Breast, lung, colon, and rectal cancers stand among the most prevalent and deadly forms of the disease.  While breast cancer primarily affects women, lung, colon, and rectal cancers impact both men and women.10  Early detection and proactive health measures play pivotal roles in reducing the risks associated with these. 

3. Cardiovascular Disease  

Cardiovascular diseases, like heart attack and strokes, are the leading causes of death, responsible for 1/3 of all deaths.7  Unhealthy diet, lack of physical activity, smoking, and excessive alcohol use are major behaviors that increase the risk of these diseases.  These behaviors can lead to issues like obesity, impaired glucose metabolism, and hypertension (high blood pressure).   

All these risk factors are inter-related with metabolic syndrome and the progression of metabolic disorder. 10 Persistent inflammation can increase the risk of cancer.  When inflammation becomes chronic, it may damage healthy tissue and cause cells to reproduce rapidly, creating an environment that promotes cancerous tumor growth.11 

4. Neurodegenerative Disease 

Chronic inflammation in the brain, known as neuroinflammation, is associated with neurodegenerative diseases (e.g. Alzheimer’s disease, Parkinson’s disease), especially in older adults.12  This persistent low-level inflammation is linked to cognitive decline and dementia, making it the 6th leading cause of death.  More alarmingly, neurodegenerative disease is among the fastest growing cause of death among chronic ailments.13 

Alzheimer's, accounting for up to 70% of cases, contributes significantly to this statistic.  Women are disproportionately affected as two-thirds of cases, higher risk of this disease, and higher likelihood of being caregivers.14  Older age is a well-known risk factor, but metabolic health factors are important contributors, like high blood pressure (hypertension), high blood sugar (diabetes), being overweight or obese, as well as poor diet, physical inactivity, social isolation, and depression.14  The disease often starts early, progressing under the radar with no reliable biomarkers that are available for primary care physicians to monitor.  Also, and unfortunately, there are no highly effective drugs, only minor slowdowns, and the toll on cognitive abilities, families, caregivers, and finances is immense. 

Corralling the Four Horsemen through Our Life Choices 

Preventing the development of these diseases involves understanding their risk factors, many of which are within our control.  Keep in-mind how metabolic health and chronic inflammation can contribution to overall health.  Modifiable risk factors such as adopting a healthy diet, ensuring quality sleep, managing health conditions, staying physically active, nurturing social connections, and supporting mental health are crucial steps.  These choices empower us to take charge of our well-being.   

Stay tuned for more in-depth insights on these factors in our future articles! 

When it comes to neurodegenerative diseases, your diet plays a pivotal role, and adopting the Mediterranean and MIND diets can significantly reduce your risk by ½ when strictly adhered to.15  However, maintaining an optimal diet consistently can be challenging, especially when juggling multiple risk factors.  This is where nutritional supplementation can lend a helping hand. Our supplement, RELEVATE, is crafted to encompass the 17 most frequently overlooked nutrients from these diets, addressing common gaps in the average American diet.  It serves as a comprehensive tool to support long-term brain health, evolving into an essential part of your lifelong brain health regimen.  Learn more and shop here for a proactive approach to brain health.  


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  2. Pahwa R, Goyal A, Jialal I. Chronic Inflammation. [Updated 2023 Aug 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: 
  3. Keltikangas-Järvinen, L. (2007). Metabolic Syndrome. Encyclopedia of Stress, 717–721. 
  4. Metabolic Syndrome - What Is Metabolic Syndrome? | NHLBI, NIH. (n.d.). Retrieved January 1, 2024, from 
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  9. Gyamfi, Jones et al. “Cancer as a Metabolic Disorder.” International journal of molecular sciences vol. 23,3 1155. 21 Jan. 2022, doi:10.3390/ijms23031155 
  10. Tune, Johnathan D et al. “Cardiovascular consequences of metabolic syndrome.” Translational research : the journal of laboratory and clinical medicine vol. 183 (2017): 57-70. doi:10.1016/j.trsl.2017.01.001 
  11. Singh, Nitin et al. “Inflammation and cancer.” Annals of African medicine vol. 18,3 (2019): 121-126. doi:10.4103/aam.aam_56_18 
  12. Zhang, W., Xiao, D., Mao, Q. et al. Role of neuroinflammation in neurodegeneration development. Sig Transduct Target Ther 8, 267 (2023). 
  13. 2023 Alzheimer’s disease facts and figures. (2023). Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association, 19(4), 1598–1695. 
  14. Dementia. (n.d.). Retrieved December 28, 2023, from 
  15. Morris, M. C., Tangney, C. C., Wang, Y., et al., MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimer’s and Dement., 2015, 11, 1007–1014. 
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