Is Healthy Circulation Core to Feeling Your Best?

The Circulatory System: Macrocirculation and Microcirculation

The term “circulatory system” is often used interchangeably with “cardiovascular system” to describe the system that comprises the heart and blood vessels, including arteries, veins, and capillaries. However, when many people hear the phrase “cardiovascular system,” they think of the heart only. “Circulatory system,” on the other hand, is an encompassing term that describes the heart and the system that delivers blood and nutrients to cells and tissues and carries away waste products.

Specifically, the circulatory system carries red blood cells (RBCs), which deliver oxygen to tissues for cellular energy production and carry carbon dioxide away from tissues for disposal via the lungs and breath. However, blood vessels aren’t simply inert tubes that carry blood; they are dynamic structures that influence the health and function of the circulatory system.

You can think of the circulatory system in two parts:

  • Macrocirculation, referring to large blood vessels like arteries and veins that carry blood to and away from the heart; and
  • Microcirculation, the “final destination” of the cardiovascular system (1), consisting of much smaller blood vessels, including arterioles, venules, and capillaries. Here, oxygen is delivered to cells, and carbon dioxide and other wastes are off-loaded from tissues onto RBCs for disposal.(2) Interestingly, microcirculation is also responsible for delivering hormones and nutrients to cells and facilitates the activity of the immune system.

Healthy arteries and veins are crucial but without proper microcirculation, it is difficult for our bodies to function properly, setting the stage for disease.

Disease and the Role of Circulation

Cardiovascular disease is currently the leading cause of death in the United States and globally. (3, 4) Shockingly, one person in the U.S. dies every 36 seconds from cardiovascular disease. (5) The prevailing dogma for the past 70 years has been that cholesterol causes heart disease; this dogma is referred to as the “diet-heart hypothesis.” (6) However, a reappraisal of the research, and emerging new evidence, indicates that cholesterol is but one piece of the cardiovascular disease puzzle. Instead, the causes of the epidemic of cardiovascular disease require a more nuanced approach than simply tackling saturated fat and cholesterol. Circulatory system dysfunction, including problems with macro- and microcirculation, is emerging as a primary driver of cardiovascular disease.

When the lining of blood vessels becomes damaged and dysfunctional, a condition known as “endothelial dysfunction,” ensues. Endothelial dysfunction increases the generation of harmful reactive oxygen species (ROS) inside blood vessels, which reduces nitric oxide production needed for normal vasodilation. ROS also triggers inflammation, clotting, and cholesterol deposition in the blood vessel lining. (7, 8) This means that cholesterol alone may not be the driver of cardiovascular disease but rather a molecule that gets caught up in the tussle when the endothelial lining of blood vessels becomes damaged. An unhealthy circulatory system, in turn, can create cardiovascular complications, setting the stage for high blood pressure, atherosclerosis, and stroke.

Compromised circulation doesn’t just affect the heart and arteries. It also influences the brain and kidneys, which rely on robust blood circulation for healthy function. (9, 10, 11, 12, 13) Endothelial damage and compromised circulation also play a role in Raynaud’s syndrome, a condition associated with autoimmune diseases that decreases blood flow to the fingers, ears, and toes, resulting in changes in skin color, numbness, and coldness. (14) Interestingly, scientists theorize that microcirculatory dysfunction may also drive aging by impairing nutrient delivery and waste disposal to and from cells respectively. (15) Maintaining a healthy blood circulation is thus vital for protecting against multiple, interrelated chronic health conditions.

Men, Women, Hormones, and Circulation

Men and women have many overlapping risk factors for CVD, including obesity and high blood pressure, but also experience several unique CVD risk factors, many of which influence the circulatory system. In women, estrogen is essential for maintaining healthy endothelial function, affecting the health of the blood vessel wall. (16) The protective effects of estrogen on the vasculature may explain why women experience a significant increase in CVD risk after menopause when estrogen levels decline significantly. (17, 18) In men, low testosterone levels can lead to increased inflammation and decreased nitric oxide availability, resulting in possible damage to the vascular endothelium and impaired circulation. (19)

Factors That Damage Macro- and Microcirculation

Sedentary Lifestyle

A sedentary lifestyle involving a lot of sitting, standing, and little exercise damages microcirculation. Even short periods of physical inactivity, including two weeks of walking less than 10,000 steps per day and sitting 100 minutes more per day than usual, causes a significant decline in endothelial function. (20) At least 25 percent of U.S. adults are completely sedentary, not engaging in any physical activity at all. (21)

High Blood Sugar

High blood sugar decreases the “branches” of the microcirculation “tree,” impairing blood flow, oxygen and nutrient delivery, and waste elimination via the smallest of our blood vessels, called capillaries, which can become damaged from high circulating glucose levels. (22) This is why type 2 diabetes can cause damage to not only the heart, but to the eyes, and extremities.  

High Uric Acid Levels

Uric acid is a byproduct of the metabolic breakdown of purines. Purines are natural substances found in specific foods, such as organ meats, and are also synthesized in the body. Factors that raise uric acid include high fructose and sugar intake because both factors stimulate purine metabolism, and the purines are subsequently broken down into uric acid. Excess uric acid damages the vascular endothelium, driving circulatory system dysfunction. (23)


Exposure to ambient air pollution, such as car exhaust and factory smoke, is associated with an increased incidence of microvascular diseases such as peripheral neuropathy and chronic kidney disease. (24) Alarmingly, the adverse effects of air pollution on the circulatory system may begin before we are born and in early childhood. (25)

Nutrient deficiencies

Insufficient intakes of vitamins B12, B6, and folate increase homocysteine, an amino acid that is a normal part of the body’s methylation cycle. However, when homocysteine is too high, it can damage the endothelial lining of blood vessels, making it a common biomarker for cardiovascular disease. Ensuring adequate intakes of B12, B6, and folate helps the body metabolize homocysteine properly, so it doesn’t accumulate. (26)

Vitamin C is needed to build and repair the collagen components of blood vessels and protects blood vessels against oxidative stress. Vitamin C deficiency can thus impair microcirculation. (27)


When the immune system turns against the body and starts to create antibodies to its own cells and tissues, autoimmunity results. Proteins made by the immune system that attack the body’s cells and tissues are called autoantibodies and can sometimes be directed against components of the circulatory system. For example, antiphospholipid antibodies attack the endothelial lining of blood vessels, increasing the risk of blood clots. In addition, anti-laminin antibodies produced in the bodies of people with Raynaud’s syndrome and scleroderma attack the collagen inside blood vessels. (28) In cases where autoantibodies are attacking the circulatory system, addressing the underlying causes of autoimmune disease and balancing the immune system is crucial.


Certain infectious microorganisms can also damage the microcirculation. For example, Rickettsia, a bacterium transmitted by ticks, acutely damages the microcirculation in a condition called “vasculitis.” (29) More recently, SARS CoV 2, the cause of the COVID-19 pandemic, has been found to cause microvascular damage. (30) Preventing and treating chronic infections may be necessary for long-term circulatory system health.

Genetics – Low Nitric Oxide

Specific single nucleotide polymorphisms (SNPs), common genetic variants, can decrease vascular production of nitric oxide (in the case of the eNOS variant) and/or paraoxonase 1 (in the case of PON1 variants), an important antioxidant enzyme, rendering blood vessels more susceptible to damage. (31, 32) Therefore, people who carry eNOS or PON1 variants may benefit from diet, supplementation, and lifestyle measures that increase nitric oxide and paraoxonase synthesis.

Taking Charge of your Circulatory Health

A healthy circulatory system is a prerequisite for overall cardiovascular health. By avoiding factors that hinder healthy macro- and microcirculation, you can maintain a circulatory system that efficiently energizes and nourishes your cells and tissues, supporting whole-body health. Be sure to check out part 2 of this article series, Taking Charge of your Circulatory Health, where we discuss lifestyle hacks and the most researched supplemental botanicals and nutraceuticals to best support healthy circulatory and cardiovascular function.


  1. Heart disease facts. Centers for Disease Control and Prevention. Reviewed. Reviewed February 7, 2022. Accessed June 27, 2022.
  2. Cardiovascular diseases (CVDs). World Health Organization. Published June 11, 2021. Accessed June 27, 2022.
  3. De Souza RJ et al. Intake of saturated and trans unsaturated fatty acids and risk of all-cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ. 2015; 351: h3978.
  4. Lordan R et al. Dairy fats and cardiovascular disease: Do we really need to be concerned? Foods. 2018; 7(3): 29.
  5. Nutrition and physical activity: Current Guidelines. Updated August 24, 2021. Accessed June 27, 20222.
  6. Srour B et al. Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Santé). BMJ. 2019; 365: I1451.
  7. Bhardwaj B et al. Death by carbs: Added sugars and refined carbohydrates cause diabetes and cardiovascular disease in Asian Indians. Mo Med. 2016; 113(5): 395-400.
  8. Yang Q et al. Added sugar intake and cardiovascular diseases mortality among US adults. JAMA Intern Med. 2014; 174(4): 516-524.
  9. Lindqvist PG et al. Low sun exposure habits is associated with a dose-dependent increased risk of hypertension: a report from the large MISS cohort. Photochem Photobiol Sci. 2021; 20(2): 285-292.
  10. Wallis DE et al. The “sunshine deficit” and cardiovascular disease. Circulation. 2008; 118: 1476-1485.
  11. Vallat R et al. Broken sleep predicts hardened blood vessels. PLoS Biol. 2020; [online].
  12. Judd SE and Tangpricha V. Vitamin D deficiency and risk for cardiovascular disease. Am J Med Sci. 2009; 338(1): 40-44.
  13. Rosique-Esteban N et al. Dietary Magnesium and Cardiovascular Disease: A Review with Emphasis in Epidemiological Studies. Nutrients. 2018; 10(2): 168.
  14. Von Shacky C. Omega-3 index and cardiovascular health. Nutrients. 2014; 6(2): 799-814.
  15. Stampfer MJ et al. Primary Prevention of Coronary Heart Disease in Women through Diet and Lifestyle. NEJM. 2000; 343: 16-22.
  16. Chiuve SE et al. Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and antihypertensive medications. Circulation. 2006; 114(2): 160-167.
  17. Taniyama Y and Griendling KK. Reactive oxygen species in the vasculature. Hypertension. 2003; 42: 1075-1081.
  18. Kramer B et al. Western diet triggers Toll-like receptor 4 signaling-induced endothelial dysfunction in female Wistar rats. Heart Circ Physiol. 2018; [online].
  19. Chen K et al. Nitric Oxide in the Vasculature: Where Does It Come From and Where Does It Go? A Quantitative Perspective. Antioxid Redox Signal. 2008; 10(7): 1185-1198.
  20. Wu X et al. Baseline Insulin Resistance Is a Determinant of the Small, Dense Low-Density Lipoprotein Response to Diets Differing in Saturated Fat, Protein, and Carbohydrate Contents. Nutrients. 2021; 13(12): 4328.
  21. Johnson RJ et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension. 2003; 41: 1183-1190.
  22. Heart disease: Differences in men and women. Accessed July 27, 2022.
  23. Menopause and heart disease. org. Reviewed July 31st, 2015. Accessed June 27th, 2022.
  24. Moolman JA et al. Unravelling the cardioprotective mechanism of action of estrogens. Cardiovasc Res. 2006; 69(4): 777-780.
  25. Mu F et al. Endometriosis and risk of coronary heart disease. Circulation. 2016; 9(3): 257-264.
  26. Young L and Cho L. Unique cardiovascular risk factors in women. Heart. 2019; 105(21): 1656-1660.
  27. Heinze-Milne S et al. Low testosterone concentrations and risk of ischaemic cardiovascular disease in ageing: not just a problem for older men. Lancet. 2022; 3(2): E83-E84.
  28. Leening MJG et al. Comparison of cardiovascular risk factors for coronary heart disease and stroke type in women. JAHA. 2018; 7: e007514.
  29. Ginsberg HN. Insulin resistance and cardiovascular disease. J Clin Invest. 2000; 106(4): 453-458.
  30. Layman DK et al. Increased dietary protein modifies glucose and insulin homeostasis in adult women during weight loss. J Nutr. 2003; 133(2): 405-410.
  31. Muller M et al. Gastrointestinal transit time, glucose homeostasis and metabolic health: Modulation by dietary fibers. Nutrients. 2018; 10(3): 275.
  32. Weickert MO et al. Metabolic effects of dietary fiber consumption and prevention of diabetes. J Nutr. 2008; 138(3): 439-442.
  33. Mcintosh M et al. A diet containing food rich in soluble and insoluble fiber improves glycemic control and reduces hyperlipidemia among patients with type 2 diabetes mellitus. Nutr Rev. 2001; 59(2): 52-55.
  34. Pagliaro B et al. Phytochemical compounds and protection from cardiovascular diseases: A state of the art. Biomed Res Int. 2015; 2015: 918069.
  35. Shaw SD et al. PCBs, PCDD/Fs, and organochlorine pesticides in farmed Atlantic salmon from Maine, eastern Canada, and Norway, and wild salmon from Alaska. Environ Sci Technol. 2006; 40(17): 5347-5354.
  36. Grandner MA and Malhotra A. Sleep as a vital sign: why medical practitioners need to routinely ask their patients about sleep. Sleep Health. 2015; 1(1): 11-12.
  37. Javaheri S and Redline S. Insomnia and risk of cardiovascular disease. Chest. 2017; 152(2): 435-444.
  38. Physical activity and health: A report of the surgeon general. Centers for Disease Control and Prevention. Reviewed September 17, 1999. Accessed June 27, 2022.
  39. Piercy KL and Troiano RP. Physical activity guidelines for Americans from the US Department of Health and Human Services. Circulation. 2018; 11: e0005263.
  40. Dar T et al. Psychosocial stress and cardiovascular disease. Curr Treat Options Cardiovasc Med. 2019; 21(5): 23.
Share on facebook
Share on twitter
Share on email
Share on print
Share on google

Join Dr. Shade's Community

Join our community and be the first to know about Dr. Shade’s articles, podcasts and events.