Citrus for Heart Health:

       The vast majority of people have a general understanding that citrus fruits, such as oranges or lemons, can offer significant health benefits and are a good dietary choice for those interested in improving their health and longevity. However, not everyone has a comprehensive understanding about the true extent of impact that the consumption of citrus fruits can have on a person’s overall longevity and wellbeing.

    With so many diverse facets of health being impacted and improved by the consumption of citrus, it can actually be a bit overwhelming trying to choose a specific topic to focus on. So I felt that it would be appropriate to address the number one #1 physiological system coveted as being the  pentacle of longevity……The cardiovascular system….

The primary beneficial aspects of citrus consumption for heart health being:

  • Vitamin C – (Collagen Maintenance – Stress relief)
  • Antioxidant Protection – (Decreased Fat Oxidation)
  • Blood Vessel & Arterial Function – (Improved Epithelial Health & Decreased Plaque)
  • Decreased Inflammation- (Nrf-2 modulation – Inflammatory Cytokine suppression)
  • Genome & DNA Health (Epigenetic Improvements)
  • Citric Acid Chelation – (Reduced calcification of arteries and kidneys)

    Each of these aspects of health, impacted by citrus consumption, offers its own uniquely profound implications on general longevity and wellbeing.

Vitamin C:

     Given the fact that Oranges can provide more than 70 percent of the recommended daily value(1) of vitamin C in just 100 grams, with a long durable shelf-life(allowing widespread global availability at reasonable prices), it is no wonder why they are such a common sight in virtually every supermarket across the world.

     Offering much higher concentrations of vitamin C than most of the other popular mainstream fruits; such as apples or bananas for example (which only offer a small fraction of the vitamin C content of citrus fruits), oranges are typically a good choice for getting adequate amounts of natural vitamin C at a reasonable cost, without having to resort to synthetic vitamin supplementation.

    This a well-known nutritional fact, broadly understood amongst the general public; although I think, vastly underappreciated as well. As vitamin C has extremely important health implications(2) in human physiology, yet is widely under-consumed amongst a great number of communities.

Collagen Production

     Due to the crucial role that vitamin C plays in the synthesis of collagen (3), vitamin C should be viewed as an extremely important key component for any person wishing to achieve cardiovascular efficiency and longevity.

    Since collagen is one of the most important key protein building blocks vital for the structural integrity of basically every physiological system throughout the human body, the importance of proper collagen synthesis is critical for the optimal functioning of most organs and structures.

     Vital structures such as the heart, the arteries, the veins(4), the kidneys, the lungs, the liver, and more, are all completely reliant and dependent on the proper formation of collagen. And since all of these organs work together synergistically in order to permit healthy cardiovascular functioning; it is important to ensure that healthy collagen formation is supported through adequate vitamin C consumption. An important element, commonly overlooked by those considering preventative health measures regarding cardiovascular health. 

Stress Relief

     Additionally, the consumption of vitamin C has proven to be a valuable dietary asset for the relief of psychological stress(5), a lifestyle factor which is infamous for being a major contributor to the development of various cardiovascular ailments.

    With the highest concentrations of vitamin C throughout the body being stored in the brain(6) and in the adrenal glands(hormonal stress response system), it is clear that vitamin C plays an important role in the regulation of human stress in general. Specifically having significant impact on the neuromodulation(7) of various glutamatergic, dopaminergic, cholinergic, and GABAergic transmissions and the related behaviors that stem from their regulation.

  Since high levels of stress have shown to increase oxidative damage(8), create inflammation(9), and cause genetic damage(10) (DNA/RNA dysfunction), amongst other problems, the notion that stress prevention is crucial to maintain cardiovascular health is widely accepted among the vast majority of researchers and physicians.

     As many cognitive impairments(11) and neurodegenerative disorders(12) are associated with excessive levels of oxidative stress, it is clear that controlling and minimizing oxidation and inflammation within the brain and nervous system through the consumption of adequate dietary vitamin C is important for achieving a desirable psychological state of health. Which ultimately plays a significant role in maintaining cardiovascular health and vitality. 

Antioxidant Protection

     In addition to the powerful impact(13) of vitamin C(14), each type of citrus fruit contains a unique blend of phytochemical compounds offering powerful antioxidant activity, including various polyphenols, carotenoids, and terpenes.

     These potent antioxidant compounds have displayed significant ability to improve various health biomarkers which can directly impact cardiovascular functioning (15)

     Take into consideration the flavonoid type of polyphenols for example, such as Hesperidin in oranges(16) or Naringin in grapefruits(16)). Or the terpene type phytonutrient called Limonene(17), found abundantly in lemons and limes. All of which displaying their own potent physiological antioxidant impacts

Decreased Fat Oxidation

       One of the potential health benefits that can be offered by citrus polyphenols and terpenes is a decreased rate of lipid peroxidation(18) throughout the body, which means that their consumption is very beneficial to long term health and well-being since fat oxidation is a major contributing factor towards the development of cardiovascular disease.

     This decrease in lipid peroxidation(19), caused by the consumption of citrus fruit is extremely beneficial to cardiovascular health because certain fats(lipids), such as cholesterol, are significantly more harmful and damaging to the cardiovascular system once they have been altered by oxidative damage(20). Which is crucial to understand for anyone concerned about preventing cardiovascular ailments because the accumulation of high concentrations of oxidized cholesterol derivatives, such as oxysterol, has shown to impair the function(21) of endothelial cells(artery walls) by  creating inflammation and damage through the activation of excessive cytokine and macrophage activity in an exagerated immune system response that ultimately increases blood stream membrane permeability(22),  exposing endothelium membranes to the penetration of lipids and consequently promoting the formation of foam cells(23), which directly exacerbate the progression of atherosclerosis. 

    This is in addition to the direct damage to heart cells that is caused by oxysterols. which may eventually culminate in final stage heart failure(24).

    So controlling the amount of lipid peroxidation in our bodies through the intake of sufficient and diverse antioxidant sources is vital for the effective maintenance of optimal cardiovascular health.

Blood Vessel and Arterial Function

     Furthermore, these beneficial phytonutrients found within citrus fruit can also greatly contribute to the proper maintenance and function of artery and blood vessel health.

Improved Epithelial Health

       For example Hesperidin (the predominant phytonutrient found in oranges), has proven to protect blood vessel health (25) and enhance arterial function due to its ability to improve endothelial performance.

     Since various phytonutrient compounds in citrus have shown to increase nitrous oxide production(25) of endothelial cells, promoting vascular dilation and reducing inflammatory biomarkers; the consumption of citrus can be a valuable asset that can contribute to a person’s overall cardiovascular wellbeing.

    And given the fact that hesperidin has shown to decrease aortic stiffness(26) in age-impacted arteries and blood vessels, it is reasonable to assume that the general risks for adverse cardiovascular events would also decrease as well as a direct result. 

      

Decreased Plaque Accumulation

       In regards to the actual formation of arterial plaque; the term “thrombocyte platelet aggregation” refers to the clumping together of blood platelets, which are the small blood cells which are commonly involved  in blood clotting,

     This physiological mechanism can be a major contributing factor towards the developments of arterial plaque deposits which characterize various cardiovascular diseases.

    This excessive platelet aggregation can directly contribute to the formation of blood clots and fat-based plaque deposits in arteries, which directly leads to a higher risk of cardiovascular events such heart attacks and strokes.

 

       So, since certain phytonutrients(27) and organic acids(28) found in citrus have shown to decrease platelet aggregation(29) a key mechanism responsible for promoting the accumulation of harmful artery plaques), the consumption of fruits or juices can directly decrease the risk of adverse cardiovascular events as a result of its interferences with platelet signaling pathways, including the inhibition of platelet adhesion molecules and the suppression of platelet release reactions.

Decreased Hypertension

     Also, hypertension (or high blood pressure) is another common contributing factor to adverse cardiovascular events. With chronic long term periods of high blood pressure creating strain on the heart muscle and potentially causing damage to arteries and blood vessels.

     Althoough, due to the fact that certain phytonutrients in citrus  fruit have shown to promote vasodilation and blood vessel relaxation(30); the consumption on citrus fruits and juices can significantly help to reduce blood pressure(31) in individuals experiencing symptoms of hypertension. Ultimately lowering overall risk factors for the development of more serious complications.

Decreased Inflammation

     Additionally, another primary contributing factor to the deterioration of cardiovascular health is the presence of excessive inflammation(32) throughout the body; as inflammation can disrupt several signaling pathways(33) and intracellular communication mechanisms at the molecular level, ultimately creating detrimental dysfunction of various physiological mechanisms within the cardiovascular system.

      Which can be effectively ameliorated through frequent citrus consumption due to the high concentrations of hesperidin found in oranges and tangerines.

     Given hesperidin’s impressive ability to modulate Nrf-2(34) transcription factors (an important intracellular communication molecule) and increase the production of various endogenous antioxidant(35) enzymes(such as glutathione-GPx and superoxide dismutase-SOD), the consumption of citrus fruits and juices can directly protect the cell-walls of arteries from being damaged by oxidative stress and over-active immune cells(36), that can often result from excessive cytokine signaling(37)(commonly caused by high levels of inflation).

     So due to the fact that Nrf-2 has direct regulatory impact on cytokine signaling; hesperidin’s impact on Nrf-2 expression is an effective alleviator of vascular distress commonly caused by systematic inflammation and immune system malfunction.

         This is a very important because the vascular damage that is caused by the over-activity of immune cells can cause a chain reaction of molecular events that ultimately results in increased membrane permeability and amplified plaque accumulation from increased particle adhesion(38) within arteries and blood vessels. Which if gone unchecked, can eventually develop into atherosclerosis.

 

Genome and DNA Health

     Similar to almost every other biological system and process on earth, the human cardiovascular system is heavily reliant and dependent on proper genetic functioning of DNA and RNA and their relevant transcription factors. With damaged mitochondrial DNA(39) proving to be an important potential contributing factor in the development and progression of various cardiovascular diseases.

     This is because DNA contains the instructions for the production of all necessary proteins and molecules involved in cardiovascular functioning, such as relevant enzymes, receptors, and structural proteins. Including those responsible for blood vessel dilation, constriction, and inflammation. Which ultimately support the repair and regeneration of aging blood vessels.

 

     So the maintenance of healthy DNA function ensures the proper regulation of gene expression and allows for the appropriate synthesis of these cardiovascular-related molecules

    Which is important because multiple bioactive phytonutrients in citrus, such as hesperidin(40) or limonene(41), have shown to display DNA-protective(42) properties and display epigenetic impact on cellular health(43) so it becomes quite clear that citrus consumption can offer substantial genetic benefits to long term cardiovascular health and vitality as well.

Citric Acid Chelation / Anti-calcification

     Finally, on a more abstract note, I would like to mention one compound in particular which I believe is highly underestimated and underappreciated among the general public. Which is Citric Acid.

    It is the most abundant organic acid commonly found in all citrus fruits, often over-looked in regards to its nutritional impact and health implications.

     Commonly used in plumbing and cleaning products for its ability to remove calcium based mineral deposits on various surfaces that are in frequent contact  with hard-water flows; the natural version found in citrus fruits actually has a similar ability(44) to bind to excess calcium and remove it from the body.

     This is so important in relation to heart health because of the major role that calcium often plays in the formation of arterial plaque deposits. With higher arterial calcification(45)  scores showing heavy correlation with increased risk for adverse cardiovascular events.

     Yet, given the very long term and subtle nature of calcium deposition in arteries, the amount of definitive citrate research performed on human subjects’ remains limited due to the high cost and impracticality of performing such long term human trials with all of the variable controls involved.

     Although there are a few compelling studies available which have shown promising results in their research results: such as one study performed on 18 hemodialysis patients showing a substantial reduction in the amount of arterial calcification(46) accumulated after one week of treatment with citric acid treated dialysis fluid.

     Plu,s other studies have shown citric acids value in the decalcification of thyroids(47) or in the decalcification of the kidneys(48), in short term trials.

Conclusion

     So, in conclusion, we can confidently ascertain the fact that many of the known health benefits provided by citrus fruits can be attributed to the abundant amounts of phytonutrients and organic acids found within the pulp and juice..

      With each phytochemical compound offering its own unique mechanisms of actions, greatly beneficial to many of our various biological processes.

      These nutrients have shown to have profound effects on cardiovascular function and have proven to work together synergistically with each-other in order to improve the overall functioning of our bodies’ natural endogenous detoxification pathways and to ultimately facilitate an increase in our capacity for regenerative healing.

    And thankfully, the vast majority of people have the access and ability to experience these impressive health boosting properties of their unique blends nutrients found in so many citrus fruits around the world.

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++Additional Reading

** Testai L, Calderone V. Nutraceutical Value of Citrus Flavanones and Their Implications in Cardiovascular Disease. Nutrients. 2017;9(5):502. Published 2017 May 16. doi:10.3390/nu9050502Nutraceutical Value of Citrus Flavanones and Their Implications in Cardiovascular Disease – PMC (nih.gov)

** Xiong H, Wang J, Ran Q, et al. Hesperidin: A Therapeutic Agent For Obesity. Drug Des Devel Ther. 2019;13:3855-3866. Published 2019 Nov 12. doi:10.2147/DDDT.S227499Hesperidin: A Therapeutic Agent For Obesity – PMC (nih.gov)

** Lv X, Zhao S, Ning Z, et al. Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health. Chem Cent J. 2015;9:68. Published 2015 Dec 24. doi:10.1186/s13065-015-0145-9 Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health – PMC (nih.gov)

** Mas-Capdevila A, Teichenne J, Domenech-Coca C, et al. Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability. Nutrients. 2020;12(5):1488. Published 2020 May 20. doi:10.3390/nu12051488 Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability – PMC (nih.gov)

** Miles EA, Calder PC. Effects of Citrus Fruit Juices and Their Bioactive Components on Inflammation and Immunity: A Narrative Review. Front Immunol. 2021;12:712608. Published 2021 Jun 24. doi:10.3389/fimmu.2021.712608 URL Hyperlink: Effects of Citrus Fruit Juices and Their Bioactive Components on Inflammation and Immunity: A Narrative Review – PMC (nih.gov)

** Homayouni, F., Haidari, F., Hedayati, M., Zakerkish, M., & Ahmadi, K. (2018). Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2 diabetes; a randomized double-blind controlled clinical trial. Phytotherapy research : PTR, 32(6), 1073–1079. https://doi.org/10.1002/ptr.6046 Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2 diabetes; a randomized double-blind controlled clinical trial – PubMed (nih.gov)

** Choe, S. C., Kim, H. S., Jeong, T. S., Bok, S. H., & Park, Y. B. (2001). Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits. Journal of cardiovascular pharmacology, 38(6), 947–955. https://doi.org/10.1097/00005344-200112000-00017Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits – PubMed (nih.gov)

** Xianchu, L., Lan, P. Z., Qiufang, L., Yi, L., Xiangcheng, R., Wenqi, H., & Yang, D. (2016). Naringin protects against lipopolysaccharide-induced cardiac injury in mice. Environmental toxicology and pharmacology, 48, 1–6. https://doi.org/10.1016/j.etap.2016.09.005Naringin protects against lipopolysaccharide-induced cardiac injury in mice – PubMed (nih.gov)

** Huang M, Deng M, Nie W, Zou D, Wu H, Xu D. Naringenin Inhibits Platelet Activation and Arterial Thrombosis Through Inhibition of Phosphoinositide 3-Kinase and Cyclic Nucleotide Signaling. Front Pharmacol. 2021;12:722257. Published 2021 Aug 12. doi:10.3389/fphar.2021.722257Naringenin Inhibits Platelet Activation and Arterial Thrombosis Through Inhibition of Phosphoinositide 3-Kinase and Cyclic Nucleotide Signaling – PMC (nih.gov)

** Den Hartogh DJ, Tsiani E. Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol. Biomolecules. 2019; 9(3):99. Biomolecules | Free Full-Text | Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol (mdpi.com)

** Pontifex, Matthew G. and Malik, Mohammad M. A. H. and Connell, Emily and Müller, Michael and Vauzour, David (2021) Citrus Polyphenols in Brain Health and Disease: Current Perspectives. Frontiers in Neuroscience,  volume 15, 1662-453X.  https://www.frontiersin.org/articles/10.3389/fnins.2021.640648 **URL Hyperlink: Frontiers | Citrus Polyphenols in Brain Health and Disease: Current Perspectives (frontiersin.org)