Spermidine, a natural polyamine, has garnered attention for its autophagy-inducing and anti-aging properties. Recent research published in Molecules explores a novel mechanism by which spermidine may contribute to cardiovascular health: its ability to inhibit the oxidation of low-density lipoprotein (LDL), a key factor in the development of atherosclerosis. First things first, let’s cover a little background.
What is LDL?
LDL, or low-density lipoprotein, is a combination of fat (lipid) and protein. The cholesterol (fat) is transported through the blood by the protein component, apolipoprotein B. This protein allows LDL particles to move through the bloodstream and deliver cholesterol to cells where it’s needed. Cholesterol itself is essential for your body, helping to build cell membranes, produce hormones like estrogen and testosterone, and make vitamin D.
Although LDL is often called "bad cholesterol," it's not inherently harmful. It plays an important role in carrying cholesterol to areas of the body where it's necessary for healthy functions. The problem arises when there’s too much LDL in your blood. If LDL levels get too high, it can deposit cholesterol in your arteries, leading to plaque buildup. Over time, this narrows the arteries and increases the risk of heart disease and stroke.
What is HDL?
HDL, or high-density lipoprotein, is often referred to as "good cholesterol" because it helps remove excess cholesterol from the bloodstream and transports it to the liver for disposal. Higher levels of HDL are associated with a lower risk of heart disease,
Why is oxidized LDL bad?
LDL oxidation happens when LDL particles react with free radicals, which are unstable molecules that can damage healthy cells by stealing electrons, leading to oxidative stress. This damage is linked to aging, inflammation, and diseases like heart disease. While free radicals are produced naturally during processes like breathing and digestion, factors like pollution, smoking, processed foods, and stress can increase their numbers. To fight free radicals, your body uses antioxidants like vitamin C, vitamin E, polyphenols, and flavonoids, which are found in fruits, vegetables, green tea, dark chocolate, and nuts. Antioxidants act like “bodyguards,” donating electrons to free radicals to neutralize them and prevent damage. When LDL becomes oxidized, it becomes more likely to stick to artery walls, causing inflammation and contributing to plaque buildup. Eating healthy, exercising, and certain supplements or medications can help keep LDL levels in check. However, while keeping LDL levels low is important, reducing oxidation is just as crucial for heart health!
How does oxidized LDL contribute to the development of atherosclerosis?
Atherosclerosis , characterized by the buildup of oxidized LDL in arterial walls, is a major risk factor for cardiovascular disease, which is now a global epidemic and the leading cause of death worldwide. When LDL particles become oxidized, they trigger an immune response, and macrophages (the patrol immune cells) move in to clean up the cholesterol. As these macrophages consume oxidized LDL, they become overloaded and turn into foam cells, which are cells filled with cholesterol. Over time, foam cells accumulate in the arteries, contributing to plaque buildup, which can narrow the blood vessels and lead to atherosclerosis.
How to avoid plaque buildup and reduce the risk of atherosclerosis?
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Integrate healthy changes in lifestyle:
Regular exercise, intermittent fasting, and quitting smoking are the most effective and sustainable ways to boost HDL function, reduce inflammation, and support overall heart health. -
Use dietary compounds:
Spermidine, omega-3 fatty acids, polyphenols (such as resveratrol and curcumin), and fiber are all beneficial for reducing inflammation, improving cardiovascular health, and helping to lower cholesterol absorption. These are safe, long-term solutions that complement a healthy lifestyle. -
Turn towards pharmaceuticals options:
In cases where lifestyle and diet alone are not enough, medications like statins, PCSK9 inhibitors, and aspirin can help lower LDL cholesterol, reduce inflammation, and prevent harmful blood clots. These should be used under medical supervision.
What this new study shows
The study by Rossmann et al. explores spermidine’s ability to directly prevent LDL oxidation, a crucial step in plaque buildup in arteries. Using an in vitro model, LDL oxidation was induced with copper ions and tested in the presence of different concentrations of spermidine. The results showed that:
- Spermidine inhibits lipid oxidation: Spermidine significantly reduced the production of lipid hydroperoxides (LPOs) and malondialdehyde (MDA), both markers of lipid oxidation.
- Spermidine suppresses protein oxidation: Spermidine also inhibited the formation of oxidation-specific immune epitopes on the protein part of LDL, showing its protective effect on both the lipid and protein components of LDL.
- Spermidine reduces cytotoxicity of oxidized LDL: LDL oxidized in the presence of spermidine caused less damage to vascular endothelial cells, suggesting a protective effect at the cellular level.
- Spermidine acts as an antioxidant: Quantum chemical calculations in the study revealed that spermidine effectively scavenges hydroxyl radicals (HO•), a reactive oxygen species involved in LDL oxidation. This scavenging action releases energy and is likely to occur spontaneously, supporting spermidine’s antioxidant role.
- Spermidine is a stronger antioxidant than alpha-ketoglutarate (a-KG): Both spermidine and a-KG exhibit antioxidant properties, but spermidine was shown to be more effective in inhibiting LDL oxidation.
Spermidine: a natural antioxidant for heart health and other chronic diseases
The findings in this study highlight the promising role of spermidine as a direct antioxidant, effectively reducing oxidative stress and preventing endothelial dysfunction, a key precursor to atherosclerosis. In addition to its well-established ability to promote autophagy, spermidine supplementation shows potential in addressing various clinical conditions associated with systemic inflammation and oxidative stress, including atherosclerosis, rheumatoid arthritis, diabetes, obesity, and hypertension.
Previous studies have linked higher dietary spermidine intake to a reduced risk of cardiovascular disease, further supporting the role of spermidine-rich diets in promoting heart health. While spermidine is naturally found in foods like soybeans, mushrooms, and whole grains, supplementation can boost its systemic availability, providing a more effective approach to harness its heart-health benefits.
As quoted from the paper: “We propose that oral supplementation of spermidine, besides its autophagy inducing effects, might help to suppress the oxidation of nLDL, and, thus, the subsequent endothelial damage/atherogenesis in aging people”.
TLDR! Spermidine could be a powerful antioxidant against atherosclerosis
The study by Rossmann et al. provides strong evidence that spermidine can directly inhibit LDL oxidation, revealing a novel mechanism behind its effects on preventing plaque buildup in arteries. While spermidine’s ability to promote autophagy remains its primary health benefit, this study suggests that spermidine is also a powerful antioxidant.
Atherosclerosis, a leading cause of cardiovascular diseases, is driven by the accumulation of oxidized LDL in arterial walls. By preventing LDL oxidation, spermidine could play a critical role in reducing the formation of atherosclerotic plaques, ultimately lowering the risk of heart disease.
More clinical research is essential to unlock the full potential of spermidine supplementation, especially in its promising role in preventing cardiovascular disease.
Disclaimer: The information provided in this blog is based on the findings of the referenced study and general knowledge. Always consult with a healthcare professional before starting any new dietary supplement.
