Intermittent fasting Reverses Endothelial Dysfunction

This article presents three studies showing intermittent fasting could improve endothelial function.

The endothelium is the inner lining of the blood vessels, and the cells in it do a full-time job of keeping it smooth, distensible, and open to maintain adequate organ perfusion, and lower blood pressure, resulting in less work for the heart.

The Magical Endothelium

The long-term effects of healthy blood vessels are the prevention of end-organ damage and a lower incidence of heart attacks, strokes, and heart failure.

If the arteries cannot be adequately maintained, then atherosclerosis starts.

A sedentary lifestyle and a bad diet can damage the endothelium. Very high blood sugar after a meal, also called post-prandial hyperglycemia, causes inflammation from oxidative stress and damage to all arteries, large and small.

If persistent, atherosclerosis thickens, the arteries become calcified and cardiovascular diseases like strokes and heart attacks ensue.

Intermittent fasting and blood vessel health

Intermittent fasting has been shown to have several health effects (see related articles below). Fasting is not hard to do since fasting time includes the sleeping period.

A 16-hour fast can be done with the last meal being 7 pm and the next meal at 11 am the next day. Unsweetened liquids like water, black coffee, and tea can be drunk during fasting.

Ramadan

Ramadan is one of the five pillars of Islam. During Ramadan, faithful followers of the Islamic faith do not eat, drink or smoke from pre-sunrise to sunset. Depending on where they live, it can last from 12 to 18 hours.

Four studies that compared endothelial function before, during, and after Ramadan are presented here.

Fasting Increases Nitric Oxide

Nitric oxide (NO) secreted by endothelial cells performs many functions to maintain endothelial integrity. Lack of NO is one of the primary reasons why endothelial dysfunction starts.

The effect of Ramadan fasting on nitric oxide levels is the objective of the first study that involved 21 males who may benefit from higher NO levels.

That’s because they already have cardiovascular diseases, which include coronary artery disease and cerebrovascular or peripheral arterial diseases.[1]

Their results showed that nitric oxide levels in the participants after Ramadan fasting significantly increased compared with the baseline value.

The nitric oxide increase is due to the lowering of a substance called asymmetric dimethylarginine (ADMA) due to fasting. Typically, ADMA reduces nitric oxide production, leading to endothelial dysfunction and cardiovascular diseases.[1]

The vascular endothelial growth factor (VEGF) is another molecule they measured. VEGF increases the production of nitric oxide in the vascular endothelial cells. Fasting increased the levels of VEGF in their study. [1]

Negatively charged free radicals are produced in states of endothelial dysfunction. These free radicals oxidize LDL in lipid peroxidation resulting in malondialdehyde (MDA) formation. High MDA levels are seen in cardiovascular diseases. [1]

The study showed that MDA was decreased in the fasted group. The authors also note that while the changes in NO and ADMA were statistically significant, the VEGF and MDA changes were not. [1]

Still, the VEGF and MDA changes are consistent with the nitric oxide increase and indicate that fasting benefits people with established cardiovascular diseases. [1]

Fasting Lowers Blood pressure.

As nitric oxide increases, the blood vessels can dilate more readily and lower blood pressure. That’s the result of the study that involved fourteen healthy middle-aged men. [4]

They found that during the Ramadan fast, blood pressure decreased while blood glucose and LDL-cholesterol increased. 

The rise in the BUN could be from dehydration since they are not allowed to drink. The BUN is not expected to rise in people with adequate liquid intake during fasting. 

The glucose increase could be explained by the type of food eaten after the daily fast during Ramadan, which usually contains carbohydrates and sweets.

About the higher LDL levels. I have to comment that the authors did not look at the particle size of the LDL. That is important because there are two major types of LDL particles. The small-dense and the large-fluffy LDL particles.

Small-dense LDL is bad because it is associated with a greater coronary risk. In contrast, high numbers of large-fluffy LDL are good because they help removes cholesterol deposits from the arteries.

Klempel et al. showed that alternate-day fasting increases the LDL particle size and decreases the proportion of the small LDL particles. This applies to both high and low-fat diets with alternate-daily fast. [2]

Learn more about the nuances of LDL at – LDL: “Bad Cholesterol” is Not All Bad.

Fasting increases the arterial diameter.

The research by Khouchab et al. found that the diameter of the brachial artery in the arm showed a significant increase during the fasting period. [3]

The measurement was made using flow-mediated dilatation (FMD). FMD uses an ultrasound machine to measure the diameter of the brachial artery in the arm as a blood pressure cuff is released.

The study included eight patients with endothelial dysfunction (40 to 70 years old, with an average age of 58 years old. 7 women and three men). Ten subjects with normal endothelial function served as control. (4 males and seven females, ages between 24 and 29). [3]

FMD was done three times in all. The first was one week before Ramadan. The second was during the third week of Ramadan, and the third was two weeks after Ramadan. [3]

Results showed that Ramadan fasting caused a significant increase in the percentage of brachial artery diameter. Six out of eight in the study group and six out of ten increased the diameter of their brachial arteries. [3]

Fasting improves coronary artery flow.

Ramadan fasting can increase the flow in the arteries supplying the heart muscles. Gocer et al. measured the coronary flow by counting the TIMI frame counts in 67 patients.

Summary

As shown by Ramadan fasting in this article, intermittent fasting can improve vascular health from the molecular level and be observed clinically with lower blood pressures, larger arterial diameters, and improved coronary arterial flow.

Endothelial dysfunction arises from after-meal high blood sugar or post-prandial hyperglycemia. It can happen to all, even with or without diabetes.

Aside from intermittent fasting, there are other ways to prevent post-prandial hyperglycemia.

• Blood Glucose Spike and its Prevention
• Veggies Meat Carbohydrate Sequence Prevents After Meal Sugar Spike
• Walk After Meals to Prevent Sky High Blood Sugars

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1. Yousefi, B., Faghfoori, Z., Samadi, N. et al. The effects of Ramadan fasting on endothelial function in patients with cardiovascular diseases. Eur J Clin Nutr 68, 835–839 (2014). https://doi.org/10.1038/ejcn.2014.6
2. Klempel MC, Kroeger CM, Varady KA. Alternate day fasting increases LDL particle size independently of dietary fat content in obese humans. Eur J Clin Nutr. 2013 Jul;67(7):783-5. doi: 10.1038/ejcn.2013.83. Epub 2013 Apr 24. PMID: 23612508.
3. Khouchab, M. & Fihri, L. & Jourani, S. & Charei, N. & Hattaoui, M.. (2020). The Effect of Fasting During Ramdan on Endothelial Function. SAS Journal of Medicine. 06. 128-132. 10.36347/sasjm.2020.v06i04.004.
4. Esmaeilzadeh, F Nina & Borne, Philippe. (2016). Does Intermittent Fasting Improve Microvascular Endothelial Function in Healthy Middle-aged Subjects? Biology and Medicine. 8. 10.4172/0974-8369.1000337.
5. Gocer H, Gunday M, Abusharekh M, Unal M. To show the effect of intermittent fasting during Ramadan on endothelial dysfunction via TIMI frame count. Niger J Clin Pract. 2021 Jun;24(6):943-947. doi: 10.4103/njcp.njcp_626_19. PMID: 34121745.
6. Chen Y, Su J, Yan Y, Zhao Q, Ma J, Zhu M, He X, Zhang B, Xu H, Yang X, Duan Y, Han J. Intermittent Fasting Inhibits High-Fat Diet-Induced Atherosclerosis by Ameliorating Hypercholesterolemia and Reducing Monocyte Chemoattraction. Front Pharmacol. 2021 Sep 30;12:719750. doi: 10.3389/fphar.2021.719750. PMID: 34658858; PMCID: PMC8517704.
7. Ciera L Bartholomew, Joseph B Muhlestein, Heidi T May, Viet T Le, Oxana Galenko, Kelly Davis Garrett, Cherie Brunker, Ramona O Hopkins, John F Carlquist, Kirk U Knowlton, Jeffrey L Anderson, Bruce W Bailey, Benjamin D Horne, Randomized controlled trial of once-per-week intermittent fasting for health improvement: the WONDERFUL trial, European Heart Journal Open, Volume 1, Issue 2, September 2021, oeab026, https://doi.org/10.1093/ehjopen/oeab026

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