Anti-Inflamatory diet: Mediterranean and Ketogenic diets

It's often noted that a Mediterranean diet is anti-inflammatory. It's often then rated better than a

ketogenic diet for that reason. So how is it a person who is on a ketogenic diet has a hsCRP of 0.2 (inflamation) and an OXLDL is 0.5? How can the person have no inflammation on a ketogenic diet? And eats plenty of beef?

The perception that a ketogenic diet is inherently inflammatory is often based on assumptions that do not account for the nuances of this way of eating or individual variability. Here’s why the ketogenic diet may be yielding such impressive anti-inflammatory results:

1. Lower Insulin and Stable Blood Sugar

• A ketogenic diet keeps blood sugar levels stable and insulin low. Chronic hyperglycemia and hyperinsulinemia are pro-inflammatory states, as they can promote oxidative stress, advanced glycation end products (AGEs), and systemic inflammation. By avoiding these spikes, her body likely experiences reduced inflammatory triggers.

2. Improved Lipid Profiles

• A ketogenic diet often reduces small, dense LDL particles and increases large, fluffy LDL, which are less atherogenic. Her low oxidized LDL (oxLDL) suggests that she’s not in a pro-oxidative state, which can be inflammatory. High oxLDL levels are associated with systemic inflammation and cardiovascular risk.

3. Increased Antioxidant Activity

• Many ketogenic foods, such as beef (rich in conjugated linoleic acid and carnitine) and non-starchy vegetables, are nutrient-dense and provide antioxidants. The body also produces more ketones (e.g., beta-hydroxybutyrate), which have been shown to have intrinsic anti-inflammatory and antioxidant properties by inhibiting the NLRP3 inflammasome.

4. Reduced Body Fat and Visceral Fat

• Excess adiposity, especially visceral fat, is a significant source of inflammation due to the secretion of pro-inflammatory cytokines like TNF-alpha and IL-6. A ketogenic diet is highly effective at reducing body fat, which lowers systemic inflammation.

5. Low Processed Food Consumption

• The ketogenic diet emphasizes whole, unprocessed foods and eliminates refined sugars, seed oils, and processed carbohydrates, all of which are linked to inflammation. Even if one eats beef regularly, it’s likely unprocessed and paired with anti-inflammatory foods like non-starchy vegetables and healthy fats (e.g., olive oil).

6. Omega-6 to Omega-3 Ratio

• While a Mediterranean diet is praised for its omega-3 content, a well-formulated ketogenic diet can also achieve an optimal omega-6 to omega-3 ratio. By avoiding processed seed oils and potentially consuming fatty fish, her inflammation markers may improve.

7. Individual Variability

• Genetics and individual metabolic responses matter. Some people thrive on a higher fat, lower carb diet because it aligns with their metabolic flexibility, insulin sensitivity, and genetic predispositions.

8. Quality of Beef Matters

• If one is eating high-quality beef (e.g., grass-fed), it contains higher levels of omega-3 fatty acids, conjugated linoleic acid (CLA), and antioxidants like vitamin E, which can contribute to lower inflammation. The common argument against beef often focuses on processed red meats or grain-fed beef.

Why Low hsCRP and oxLDL?

• HSCRP: This marker is highly sensitive to overall metabolic health. On a ketogenic diet, inflammation-related triggers like insulin resistance, oxidative stress, and poor lipid metabolism are mitigated, leading to extremely low levels of CRP.

• oxLDL: This reflects oxidative damage to LDL particles, which is reduced by stable blood glucose, low insulin, and high antioxidant availability. The diet may also support lipid integrity through nutrients like vitamin E and carotenoids from vegetables.

Key Takeaway

While the Mediterranean diet is well-documented for its anti-inflammatory properties, a well-implemented ketogenic diet can achieve similar or even superior results. It’s not the diet itself but how it’s implemented—the focus on nutrient-dense, unprocessed foods, metabolic health, and inflammation-reducing practices—that determines the outcome.

Can there be enough of a difference between the ketogenic diet and the Mediterranean diet in terms of the insulin levels they produce, such that there could be an effect on eucasinoids, where the ketogenic diet elevates levels of good eucasinoids and the Mediterranean diet does not elevate the levels of good eucasinoids because it doesn't lower insulin as much?

Yes, there is a plausible mechanism by which the ketogenic diet could lead to a greater production of “good” eicosanoids compared to the Mediterranean diet, primarily through differences in insulin levels and their downstream effects. Here’s how this works:

1. Insulin’s Role in Eicosanoid Pathways

• Insulin directly affects the enzyme phospholipase A2, which regulates the release of

arachidonic acid (AA) from cell membranes. Arachidonic acid is the precursor for both pro-inflammatory and anti-inflammatory eicosanoids.

• High insulin levels can shift the balance toward the production of pro-inflammatory eicosanoids (e.g., thromboxanes and leukotrienes) through increased activity of the cyclooxygenase (COX) and lipoxygenase (LOX) pathways.

• Conversely, low insulin levels—as seen in a ketogenic diet—can favor the production of anti-inflammatory eicosanoids (e.g., prostacyclins and resolvins) due to reduced stimulation of these pro-inflammatory enzymatic pathways.

2. Ketogenic Diet and Insulin Reduction

• A ketogenic diet significantly reduces circulating insulin levels compared to a Mediterranean diet, even when both are isocaloric. This is because the ketogenic diet minimizes carbohydrate intake, resulting in less insulin secretion overall.

• Lower insulin levels reduce the availability of AA for conversion into pro-inflammatory eicosanoids, while also promoting the production of more beneficial eicosanoids from alternative pathways, such as those derived from EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid).

3. Omega-6 to Omega-3 Balance

• Both diets emphasize healthy fats, but a ketogenic diet often eliminates high-omega-6 seed oils (a hallmark of modern Mediterranean diets that have drifted from traditional practices) while emphasizing omega-3-rich sources (e.g., fatty fish, flaxseed, or supplements). A lower omega-6 to omega-3 ratio enhances the production of anti-inflammatory eicosanoids derived from EPA/DHA rather than AA.

• The Mediterranean diet, though beneficial, may not lower omega-6 intake as effectively, particularly if modern interpretations include seed oils or processed foods.

4. Ketones and Eicosanoid Modulation

• Ketones, particularly beta-hydroxybutyrate (BHB), have anti-inflammatory properties that further modulate eicosanoid production. BHB inhibits the NLRP3 inflammasome, a key driver of inflammation, and may also directly influence the balance of eicosanoids toward anti-inflammatory prostaglandins and resolvins.

5. Potential Differential in “Good” Eicosanoid Production

• Prostacyclins (PGI2): These “good” eicosanoids promote vasodilation and inhibit platelet aggregation. They are favored in low-insulin states.

• Lipoxins and Resolvins: These are derived from omega-3 fatty acids and play a critical role in resolving inflammation. A ketogenic diet, with its reduced insulin and inflammation, supports their production.

• Thromboxanes (TXA2): These “bad” eicosanoids promote clotting and vasoconstriction. Lower insulin levels on a ketogenic diet reduce their production compared to a Mediterranean diet.

6. Mediterranean Diet Insulin Response

• While a Mediterranean diet is lower in refined carbohydrates and sugars, it typically includes moderate amounts of whole grains, fruits, and legumes, which can produce a higher postprandial insulin response compared to a ketogenic diet.

• This moderate insulin elevation, while not detrimental for many people, might still promote a relative shift toward pro-inflammatory eicosanoid production compared to the consistently low insulin levels seen with ketosis.

Conclusion

The ketogenic diet’s ability to sustain lower insulin levels appears to create a more favorable environment for the production of anti-inflammatory (“good”) eicosanoids, compared to the Mediterranean diet. This difference could help explain why some individuals experience greater anti-inflammatory benefits and metabolic improvements on a ketogenic diet, especially in terms of markers like hsCRP and oxLDL. The key lies in the profound hormonal and metabolic shifts that ketosis induces, which influence not only inflammation but also lipid metabolism and eicosanoid signaling.