DIOS (Dysmetabolic Iron Overload Syndrome): Its Connection to NAFLD and Insulin Resistance

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Along with providing information on whether DIOS supplements might be right for you, this article also links to the websites where you can buy supplements for Dysmetabolic Iron Overload Syndrome (DIOS).

Dysmetabolic Iron Overload Syndrome (DIOS) is a condition involving abnormal accumulation of iron in the body. Diet changes and nutritional supplements help to regulate iron levels and enhance overall metabolic health. This article provides information on iron overload physiology and how specific nutrients and supplements influence iron metabolism. This can help people with DIOS better manage their condition and possibly reduce the risks. This article explores the role of these supplements.

What Is Dysmetabolic Iron Overload Syndrome (DIOS)?

Dysmetabolic Iron Overload Syndrome (DIOS) is a condition where too much iron builds up in the body, particularly in the liver. It is often linked to metabolic disorders such as obesity, type 2 diabetes, and metabolic syndrome, setting it apart from hereditary hemochromatosis, which is a genetic condition that also leads to iron overload. Although the iron buildup in DIOS may not be as severe as in genetic forms, it still presents serious health risks if not properly managed.

Symptoms of Dysmetabolic Iron Overload Syndrome (DIOS) often appear slowly and can be mild, making it hard to diagnose. People might feel constantly tired, have joint pain, and experience abdominal discomfort. There might be signs of liver function issues, typically shown in abnormal liver enzyme tests during routine check-ups. A noticeable symptom is a change in skin color, with the skin becoming bronzed or grayish due to iron deposits.

DIOS usually stems from underlying metabolic issues. Insulin resistance, often seen in obesity and type 2 diabetes, increases iron absorption from food, raising the risk of iron buildup. Additionally, inflammation, common in metabolic syndrome, disrupts how the body manages iron, leading to its excessive accumulation. Lifestyle choices like eating a diet rich in iron or excessive alcohol consumption can worsen these effects.

Managing DIOS involves both addressing the iron overload as well as treating the underlying metabolic disorders. Depending on the severity of symptoms and iron levels, people may consider changing their diet, using medications to lower insulin resistance, or in some cases, using treatments like chelation therapy to remove excess iron from the body.

One common approach to managing iron overload is phlebotomy or therapeutic blood removal. This technique is often used to reduce the total iron burden in the body. Phlebotomy helps lower iron levels by removing blood containing iron-rich red blood cells. Regularly scheduled phlebotomy sessions can decrease iron stores in the body, which may reduce the risk of iron-induced oxidative damage to cells and tissues. This method is relatively simple, cost-effective, and efficient in controlling iron levels, especially in diseases where iron accumulation is a primary concern.

Catching DIOS early is crucial to prevent serious health problems like liver cirrhosis, complications from diabetes, and heart diseases. It’s important for people with metabolic health concerns to know and look out for the signs of DIOS to manage their health effectively.

How Iron Overload Damages The Cells

Dysmetabolic Iron Overload Syndrome (DIOS) causes cell damage mainly through iron-induced oxidative stress. Iron is vital for numerous biological functions, but it turns toxic when it exceeds the amounts that storage proteins like ferritin and hemosiderin can handle, especially when it builds up in tissues and organs. Here’s a closer look at how this excess iron harms cells:

• Free Iron and Reactive Oxygen Species (“Free Radical”) Production: The excess iron inside cells increases the production of reactive oxygen species (ROS). When iron is free and not bound by proteins, it interacts with hydrogen peroxide to produce highly reactive hydroxyl radicals.
• Oxidative Stress and Cellular Components: The hydroxyl radicals generated are extremely reactive and capable of damaging all types of cellular components, including lipids, proteins, and DNA. This oxidative stress can rupture cell membranes through lipid peroxidation, change proteins affecting their function, and cause mutations in DNA that may lead to cell dysfunction or death.
• Mitochondrial Damage: Mitochondria, the energy powerhouses of the cell, are particularly vulnerable to iron overload. The mitochondria use iron for electron transport and energy production. Excess iron disrupts these processes, leading to inefficient energy production and increased mitochondrial ROS production. This further increases oxidative stress and can lead to mitochondrial DNA damage and programmed cell death.
• Inflammation and Fibrosis: Chronic inflammation is a response to the ongoing cellular damage caused by iron-induced oxidative stress. In organs like the liver, which is commonly affected in DIOS, persistent inflammation due to cellular injury can lead to fibrosis, where normal tissue is replaced with scar tissue, impairing organ function.
• Impaired Cellular Repair and Regeneration: High levels of iron can overload the iron storage capacity of ferritin, leading to its saturation. This reduces the cell’s ability to sequester and neutralize free iron, perpetuating the cycle of damage. Additionally, the cellular repair mechanisms become overwhelmed or impaired due to oxidative damage, reducing the ability of cells to recover from injury and maintain normal functions.

Understanding these cellular mechanisms highlights the importance of managing iron levels in conditions like DIOS to prevent cellular damage and maintain overall cellular health. Effective management strategies can greatly reduce the harmful effects of excess iron on the body’s cells.

The Connection Between DIOS and NAFLD

Non-Alcoholic Fatty Liver Disease (NAFLD) and Dysmetabolic Iron Overload Syndrome (DIOS) are closely interconnected through their underlying metabolic disturbances, with emerging evidence suggesting that iron overload might not only be a parallel condition but could also exacerbate or even partially cause NAFLD. NAFLD is characterized by excessive fat accumulation in the liver, often associated with obesity, insulin resistance, and elevated blood sugar levels—conditions typical of metabolic syndrome. Similarly, DIOS involves an abnormal accumulation of iron in the liver and other organs, not from hereditary factors but due to metabolic imbalances.

The potential causal relationship between DIOS and NAFLD centers around the metabolic dysfunction common to both. Insulin resistance, a hallmark of these conditions, impairs the body’s ability to properly manage both glucose and iron levels, leading to their accumulation in the liver. Furthermore, iron overload in DIOS can intensify the oxidative stress and inflammation in the liver seen in NAFLD. This additional burden of iron may not only worsen liver damage but also accelerate the progression from simple fatty liver to more severe forms of liver disease, such as steatohepatitis or cirrhosis.

Hyperferritinemia is observed in one-third of patients with non-alcoholic fatty liver disease (NAFLD) and Metabolic Syndrome (MetS). The condition characterized by increased body iron stores associated with components of MetS has been defined as Dysmetabolic Iron Overload Syndrome (DIOS). DIOS represents the most frequent iron overload condition, since it is observed in 15% of patients with MetS and in half of those with NAFLD and its clinical presentation overlaps almost completely with that of dysmetabolic hyperferritinemia (DH). The pathogenetic mechanisms linking insulin resistance (IR), NAFLD and DIOS to iron overload are still debated. Dysmetabolic Hyperferritinemia and Dysmetabolic Iron Overload Syndrome (DIOS): Two Related Conditions or Different Entities? [PMID: 32003680]

Dysmetabolic Hyperferritinemia and Dysmetabolic Iron Overload Syndrome (DIOS): Two Related Conditions or Different Entities? [PMID: 32003680]

The “Cellular Fragility Hypothesis”

Ferroptosis is a recently identified form of cell death, triggered by the oxidation of fatty acids in cell membranes through reactions with iron. This oxidative process generates free radicals that damage mitochondrial membranes, leading to reduced ATP production and eventually causing cell death. Ferroptosis has been linked to age-related conditions such as type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). [PMC10886327]

The rigid structure of the saturated C15:0 molecule is crucial for stabilizing cell membranes, restoring mitochondrial function, and potentially preventing ferroptosis. The “Cellular Stability Hypothesis” suggests that optimal health and longevity require cell membranes to contain between 0.4% and 0.64% C15:0, though these specific percentages are derived from targeted studies and may not reflect a general consensus.

Researchers have proposed a “Cellular Fragility Syndrome” associated with low levels of C15:0, suggesting that levels below 0.2% of total circulating C15:0 fatty acids lead to increased cell fragility. This fragility particularly affects red blood cells, which, when broken down excessively by the liver, contribute to an iron overload that significantly increases oxidative stress. [mdpi.com/2218-1989/14/7/355]

This deficiency of C15:0 is thought to increase the vulnerability of cells to ferroptosis and related conditions like dysmetabolic iron overload syndrome, type 2 diabetes, cardiovascular disease, and NAFLD. While supplementation with C15:0 has shown potential in addressing these deficiencies and mitigating key aspects of ferroptosis, the evidence supporting the preventative capabilities of C15:0 supplementation is still in its preliminary stages. More clinical trials and research are needed to fully verify its effectiveness.

The Connection Between DIOS And C15:0 Deficiency

The connection between pentadecanoic acid (C15:0) deficiency and Dysmetabolic Iron Overload Syndrome (DIOS) is an emerging area of research, with implications that are still being fully understood. C15:0, an odd-chain saturated fatty acid primarily found in dairy fats and ruminant meats, has been associated with several beneficial metabolic effects, which could influence conditions like DIOS.

• Metabolic Regulation: Research has suggested that C15:0 might help regulate metabolism, particularly lipid and glucose metabolism. This regulation could potentially influence iron metabolism indirectly, as disturbances in metabolic health are linked to conditions like DIOS, which is characterized by iron accumulation and is often associated with metabolic syndrome and insulin resistance.
• Anti-inflammatory Properties: C15:0 has been shown to possess anti-inflammatory properties. Since inflammation can exacerbate iron accumulation and the resultant oxidative stress in tissues (a key feature of DIOS), a deficiency in C15:0 might remove a natural anti-inflammatory influence, potentially worsening the condition.
• Impact on Gut Microbiota: Research suggests that C15:0 influences the gut microbiota by promoting the growth of beneficial bacteria such as Akkermansia muciniphila and Bifidobacterium species. These bacteria are known for their roles in enhancing gut barrier integrity and regulating immune responses, which can impact iron absorption and systemic inflammation. A deficiency in C15:0 might lead to an imbalance in these beneficial microbial populations (dysbiosis), potentially affecting iron regulation and contributing to conditions like DIOS. This disruption in gut microbiota balance may influence the mechanisms controlling iron storage and mobilization, thus exacerbating issues related to iron overload.
• Direct Influence on Iron Metabolism: While there is less direct evidence, it’s conceivable that C15:0 could impact iron metabolism mechanisms directly. Since C15:0 is involved in various metabolic pathways, its deficiency might disrupt the normal regulatory processes that control iron storage and mobilization.

In summary, while the direct connection between C15:0 deficiency and DIOS is not fully established, potential pathways include impacts on metabolic health, inflammatory responses, and gut microbiota balance, all of which could indirectly influence iron metabolism. Further research is needed to clarify these relationships and to determine if supplementation or increased dietary intake of C15:0 could be beneficial in managing or preventing DIOS.

What Food and Lifestyle Factors Are Important For Managing Dysmetabolic Iron Overload Syndrome (DIOS)?

Managing Dysmetabolic Iron Overload Syndrome (DIOS) effectively involves a combination of dietary adjustments and lifestyle modifications to help regulate iron levels and improve overall health. Here’s a detailed look at important factors:

Food Factors:

• Limit Iron-Rich Foods: Reduce intake of foods high in heme iron, such as red meat, liver, and other organ meats, which are more easily absorbed by the body. Non-heme iron sources like legumes and fortified cereals should be consumed in moderation and ideally combined with foods that inhibit iron absorption.
• Increase Iron Inhibitors: Incorporate foods that naturally reduce iron absorption. To maximize the effect of these inhibitors it is best to include these foods as part of your meals especially when consuming foods high in iron.
  • Calcium: One of the most effective dietary inhibitors of iron absorption is calcium. Consuming foods rich in calcium along with iron-rich meals can significantly reduce the amount of non-heme iron absorbed by the body. Good sources of calcium include dairy products like milk, cheese, and yogurt, as well as fortified plant milks, leafy green vegetables, and tofu.
  • Polyphenols: These are compounds found in a variety of plant-based foods and beverages, notably green tea and coffee, which are known for their health benefits, including their ability to inhibit iron absorption. Polyphenols bind to iron in the digestive tract, creating a complex that is less easily absorbed. Other rich sources of polyphenols include berries, nuts, vegetables, red wine, and dark chocolate.
  • Phytates: Found primarily in whole grains, legumes, nuts, and seeds, phytates (or phytic acid) are another natural compound known to inhibit iron absorption. By binding to iron in the digestive tract, phytates reduce the bioavailability of iron for absorption, helping to manage iron levels in individuals with DIOS. Integrating foods high in phytates into meals that contain iron can be an effective strategy to prevent excessive iron accumulation.
• Enhance Phytonutrient Intake: Eat a diet rich in antioxidants and phytonutrients from fruits, vegetables, whole grains, and nuts. These compounds can help protect cells and tissues from oxidative stress associated with iron overload.
• Control Vitamin C Intake: While vitamin C is essential for general health, it enhances iron absorption. It’s important to consume it in moderation and away from iron-rich meals to prevent excessive iron uptake.

Lifestyle Factors:

• Regular Physical Activity: Engaging in regular exercise can help improve insulin sensitivity and metabolic health, which are often compromised in DIOS. Activities like walking, cycling, or swimming are beneficial.
• Avoid Alcohol and Smoking: Alcohol consumption can worsen liver damage, particularly in the context of iron overload. Smoking also contributes to oxidative stress and inflammation, worsening DIOS symptoms.
• Weight Management: Since obesity and metabolic syndrome are closely linked to DIOS, maintaining a healthy weight through diet and exercise is crucial. Weight loss in overweight individuals can significantly improve metabolic parameters and reduce iron levels.
• Regular Monitoring: Regular blood tests to monitor iron levels, liver function, and metabolic markers are crucial for adjusting dietary intake and assessing the effectiveness of lifestyle changes in managing DIOS.

What Nutritional Supplements Are Recommended For Dysmetabolic Iron Overload Syndrome (DIOS)?

When managing Dysmetabolic Iron Overload Syndrome (DIOS), it’s crucial to differentiate between supplements that should be avoided due to their potential to worsen iron overload, and those that can be beneficial in regulating iron levels and reducing harm related iron overload. Here’s a breakdown:

Supplements to Consider for People with DIOS:

• C15:0 (Pentadecanoic Acid): This 15-carbon essential saturated fatty acid is newly discovered to be essential. [PMC7235264] It enhances mitochondrial function, especially under conditions of iron overload. C15:0 reduces oxidative stress and cellular damage, improving metabolic regulation and insulin sensitivity. It also supports cardiometabolic health and immune function. Its role in maintaining mitochondrial integrity is key in managing chronic diseases like type 2 diabetes, heart disease, and nonalcoholic fatty liver disease.
• Silymarin (Milk Thistle): Known for its liver-protective effects, silymarin can aid in reducing liver inflammation and fibrosis, which are potential risks from iron deposition in DIOS. [PMC3959115]
• Vitamin E: This antioxidant helps protect cells from the damage caused by excess iron through its role in neutralizing free radicals. It can be particularly helpful in protecting against liver and heart damage. [PMID: 32810309]
• Curcumin: With strong anti-inflammatory properties, curcumin helps combat oxidative stress and inflammation associated with excess iron. [PMID: 31987259]
• Calcium Carbonate: Calcium can help reduce iron absorption when taken with meals. The calcium carbonate form is better than calcium citrate for binding iron. It doesn’t decrease the body’s iron directly but can limit additional iron uptake from the diet. [PMID: 3005669]
• Green Tea Extract: Containing catechins like EGCG, green tea extract can inhibit iron absorption and be useful in managing overall iron levels. [PMC8949532]

Supplements to Avoid for People with DIOS:

• Do NOT Take High-Dose Vitamin C: Although vitamin C is essential for health, in high doses it can increase iron absorption significantly, which can be detrimental for individuals with DIOS. It’s important to manage intake and consult with a healthcare provider to determine the right balance.
• Do NOT Take Iron Supplements: Naturally, iron supplements should be avoided unless specifically recommended by a healthcare provider, as they directly increase iron levels in the body.

When managing DIOS, it’s essential to tailor supplementation to individual needs and under medical guidance, especially to avoid unintended increases in iron levels. Regular monitoring of iron levels and liver function is also crucial to ensure that any supplement regimen is both safe and effective.

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Supplement Safety Information

Pentadecanoic acid (C15:0), Silymarin, Vitamin E, Curcumin, Calcium, and Green Tea are generally considered safe and potentially beneficial for managing Dysmetabolic Iron Overload Syndrome (DIOS).

Medication Interactions:

• Vitamin E: Enhances the effects of blood thinners like warfarin, increasing the risk of bleeding; it may also interfere with the oxidative effects of certain chemotherapy drugs, potentially diminishing their therapeutic effectiveness.
• Curcumin: Possesses blood-thinning properties that can enhance the effects of anticoagulant medications, increasing the risk of bleeding; it also stimulates stomach acid production, which may counteract the effects of acid-lowering drugs.
• Silymarin: Can lower blood glucose levels, potentially increasing the hypoglycemic effects of diabetes medications and necessitating dose adjustments to avoid low blood sugar levels.
• Calcium: Interferes with the absorption of certain antibiotics such as tetracyclines and fluoroquinolones, reducing their effectiveness; it can also reduce the absorption of thyroid hormone replacements, possibly requiring adjustments in thyroid medication.
• Green Tea: Contains vitamin K, which can counteract the effectiveness of warfarin by promoting blood clotting; its caffeine content can amplify the side effects of stimulant drugs, leading to increased heart rate and blood pressure; catechins in green tea can also inhibit iron absorption from supplements, potentially reducing their efficacy in treating iron deficiency.

Supplement Interactions:

• C15:0: Absorption of C15 supplements is limited when it is taken with fatty foods.
• Silymarin: Its effects on liver metabolism could improve how other supplements that are processed in the liver.
• Vitamin E: As a powerful antioxidant, Vitamin E can interact with other antioxidants such as curcumin and green tea catechins, potentially enhancing overall antioxidant capacity in the body.
• Curcumin: It may alter the absorption and effectiveness of fat-soluble vitamins and other antioxidants due to its influence on bile production, which is crucial for fat digestion and nutrient absorption.
• Calcium: Can bind with other minerals and vitamins, potentially reducing the absorption of other supplements taken simultaneously, such as magnesium or iron.
• Green Tea: The catechins in green tea can inhibit the absorption of minerals like iron and possibly interact with other antioxidants, affecting their bioavailability and antioxidant activity.

Food First!

Although this article discusses supplements in detail, don’t forget that we are absolutely committed to the “Food First” approach to nutrition. When it comes to your health, the totality of your eating habits far surpasses the impact of individual nutrients or any single supplement you consume. Even though this article doesn’t delve into the broader picture of your overall diet, it’s crucial to keep this element at the forefront of our minds. Your food needs to provide all the vitamins, minerals, fiber, and phytochemicals to nourish your body systems down to the cellular level.

Food choices, rather than supplements, are the most critical factors for a healthy gut microbiome. These trillions of tiny inhabitants in your gut affect your brain waves; they orchestrate your immune system. They possess the power to create molecules that can switch genes on or off and are even capable of synthesizing neurotransmitters. Opting for organic foods and steering clear of plastic packaging (including those labeled BPA-free) is a smart move to limit toxin exposure. The sum of all these parts leads to a powerful conclusion: the ultimate key to your health lies in the quality and balance of the food you consume. Supplements are secondary.

What To Eat

To Sum It Up

Making strategic changes to your diet and incorporating specific supplements can significantly improve the management of Dysmetabolic Iron Overload Syndrome (DIOS). Adjusting your intake of iron through careful dietary choices, alongside utilizing supplements like C15:0, Vitamin E, Silymarin, Curcumin, and others, can help mitigate the effects of excess iron and support overall metabolic health. These interventions aim to reduce iron accumulation, protect against liver damage, and lessen inflammation, contributing to improved health outcomes.

While the potential benefits of dietary adjustments and supplementation are promising, it’s crucial to approach DIOS management with a personalized plan tailored to your unique health needs. For accurate advice and effective dietary strategies, consider consulting with a Registered Dietitian. They can provide professional guidance, help you navigate the complexities of DIOS, and ensure that your nutritional approach supports long-term weight loss, which is critical for most people with DIOS.

This Article is Not a Substitute for Medical Advice

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