Browse the evidence

Influx of free fatty acids (FFAs) and triglyceride-rich lipoproteins into skeletal muscle induces inflammation and insulin resistance via activation of TLR4, PKC, and JNK pathways.

High levels of circulating fats, especially saturated fats, can flood into muscle cells, causing inflammation and blocking insulin. Managing blood fat levels through diet (reducing saturated fats) and exercise can help prevent this lipid-induced insulin resistance.

Lipodystrophy (loss of adipose tissue) causes the same metabolic syndrome and insulin resistance as obesity, proving that adipose tissue is essential for metabolic health.

Do not aim for extremely low body fat levels. Your body needs adipose tissue to store energy safely. If you lose too much fat, it can lead to insulin resistance and metabolic syndrome, similar to obesity. Maintain a healthy amount of fat, particularly subcutaneous fat, to support metabolic health.

Resistant Starch (RS) diets increase Ruminococcus bromii and decrease Lachnospiraceae, while Non-Starch Polysaccharides (NSP) increase Lachnospiraceae and decrease Ruminococcus.

Different fibers feed different bacteria. RS feeds Ruminococcus, while other fibers (NSP) feed Lachnospiraceae. Variety in fiber types may be needed to support diverse bacterial groups.

Short-term consumption of low-carbohydrate, high-protein weight-loss diets reduces the abundance of butyrate-producing bacteria (e.g., Roseburia, Eubacterium rectale) and lowers total SCFA levels, particularly butyrate.

If following a low-carb diet for weight loss, be aware that it may reduce beneficial butyrate-producing bacteria and SCFA levels. Consider incorporating low-FODMAP fermentable fibers if tolerated, or monitor for long-term gut health implications, as long-term adherence may increase colonic disease risk.

Consumption of peanut butter is only weakly associated with a reduced risk of coronary heart disease compared to whole nuts.

While whole nuts are strongly linked to heart health, peanut butter shows a much weaker association. This may be due to added hydrogenated fats in commercial brands. Choosing whole nuts or natural peanut butter without hydrogenated fats is likely more beneficial.

In healthy young adults undergoing nutritional transition, a higher-fat diet (40% energy) compared to a lower-fat diet (20% energy) causes unfavorable shifts in gut microbiota (decreased Faecalibacterium/Blautia, increased Bacteroides/Alistipes), reduces short-chain fatty acids, and increases plasma proinflammatory markers.

If you are young and healthy but your diet is shifting towards higher fat intake, be aware that increasing fat to 40% of your calories (while keeping calories constant) may negatively impact your gut bacteria and increase inflammation markers like CRP. Switching to a lower fat diet (20% of calories) was associated with more favorable gut bacteria (higher Faecalibacterium and Blautia) and lower inflammation.

In obesity, the accumulation of classically activated (M1) macrophages in adipose tissue drives insulin resistance through the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and the activation of stress kinases (JNK, IKK, p38 MAPK) that inhibit insulin receptor signaling.

Obesity triggers an immune response in fat tissue where immune cells (M1 macrophages) become inflamed and block insulin's ability to work. This happens because excess fat releases signals that activate these immune cells. Managing body weight and reducing fat mass can help reverse this inflammatory state and improve insulin sensitivity.

M2 macrophages in lean adipose tissue maintain insulin sensitivity by secreting anti-inflammatory cytokines (IL-10, TGF-β) and utilizing oxidative metabolism, whereas obesity shifts this balance toward M1.

Maintaining a healthy weight helps preserve M2 macrophages in fat tissue, which actively protect against insulin resistance by reducing inflammation and supporting metabolic health.

Carriers of the TM6SF2 E167K genetic variant have a significantly reduced risk of cardiovascular events (myocardial infarction and stroke) and carotid atherosclerosis due to lower circulating levels of atherogenic lipoproteins.

If you carry the TM6SF2 E167K variant, your body naturally keeps blood cholesterol lower by storing more fat in your liver. This genetic trait significantly lowers your risk of heart attacks and strokes, even if you have fatty liver. You should prioritize cardiovascular health monitoring, but the genetic risk for heart disease is actually reduced.

Population-wide restriction of dietary saturated fat intake below current levels does not reduce cardiovascular disease risk and may increase stroke risk, as evidenced by recent large-scale observational studies and meta-analyses of randomized trials.

Current evidence suggests that strictly limiting saturated fat intake for the general population does not lower heart disease risk and may even increase stroke risk. Focus on whole food sources of fat (like dairy and meat) within a balanced diet rather than aiming for a specific low-saturated-fat percentage, especially if you are replacing fats with refined carbohydrates.

CD36 fatty acid translocase drives hepatosteatosis onset and progression to NASH by increasing fatty acid influx into hepatocytes, making it a key driver of NAFLD pathogenesis.

Current research suggests that the protein CD36 plays a significant role in moving fatty acids into liver cells, contributing to fatty liver disease. While there is no specific diet protocol mentioned to target CD36 directly, the findings highlight that managing fatty acid influx is critical. Future treatments may target CD36, but for now, standard NAFLD management focusing on reducing metabolic stress is implied.

Saturated fatty acids (SFAs) are more hepatotoxic than unsaturated fatty acids (UFAs) because they induce ER stress, oxidative stress, and apoptosis more effectively.

Not all fats affect the liver equally. Saturated fats are more likely to cause liver damage and inflammation than unsaturated fats. Reducing saturated fat intake may help mitigate liver stress in NAFLD patients.

M1 macrophage/Kupffer cell polarization drives insulin resistance and NASH progression, while M2 polarization protects against it.

Liver inflammation in NAFLD is driven by immune cells (Kupffer cells) shifting into a pro-inflammatory 'M1' state. Shifting these cells to an 'M2' state is protective. While lifestyle changes help, specific micronutrients like carotenoids are being studied for their ability to force this M2 shift.

In healthy young adults, serum adiponectin and resistin concentrations are not significantly associated with total energy intake or macronutrient composition, after controlling for gender and body fat mass.

For healthy young people, changing your carb-to-fat ratio does not appear to significantly change your blood levels of adiponectin or resistin. Focus on maintaining healthy body fat levels instead, as those are the primary drivers of these hormones.

Low dietary fiber intake increases the abundance of the gut bacterium Collinsella, which is positively correlated with circulating insulin levels in overweight and obese pregnant women.

If you are overweight or obese and pregnant, ensuring adequate dietary fiber intake (aiming for >28g/day as recommended) may help maintain a healthier gut microbiota balance by keeping Collinsella levels low. This is associated with lower circulating insulin levels, which may support better metabolic health during pregnancy. Focus on increasing fiber from whole food sources rather than supplements.

High-fat diets promote obesity in humans primarily by facilitating fat storage with minimal energy cost (0-2%) compared to carbohydrate conversion to fat, which is energetically expensive (25% heat loss), making high-fat diets more efficient for weight gain.

Understand that your body handles different foods differently. Converting carbohydrates into body fat is metabolically expensive and inefficient, losing 25% of the energy as heat. In contrast, storing dietary fat as body fat is highly efficient, costing almost no energy. This metabolic difference makes high-fat diets particularly conducive to weight gain when energy intake is excessive.

The proportion of energy derived from fat in the Chinese diet has increased significantly, with over 60% of urban residents consuming more than 30% of their energy from fat by 1997.

Monitor your fat intake, especially if you live in an urban area. Aim to keep fat intake below 30% of your total energy to reduce the risk of obesity and chronic diseases.

Structurally intact plant cell walls physically encapsulate macronutrients (starch and lipids), limiting their bioaccessibility to digestive enzymes and thereby attenuating postprandial glycaemic and lipaemic responses.

To manage blood sugar and calorie intake, prioritize eating whole plant foods (like whole nuts, intact legumes, and whole grains) over processed versions (like nut butters, flours, or cooked-down grains). The physical structure of these whole foods traps nutrients inside cell walls, slowing down digestion and preventing sharp spikes in blood sugar and fat levels in your bloodstream. Processing foods (grinding, cooking extensively) breaks these walls, making the nutrients fully available and potentially causing larger metabolic responses.

A short-term (3-day) high-fat, low-carbohydrate diet increases intramyocellular lipid (IMCL) content in the tibialis anterior muscle and decreases insulin sensitivity in healthy humans.

Eating a high-fat, low-carb diet for just three days can increase the amount of fat stored inside your leg muscles and reduce your body's sensitivity to insulin. This effect was seen even without matching calories to a low-fat diet, suggesting the type of fat and carbohydrate matters.

Dysbiosis, characterized by an imbalance in bacterial ratios (e.g., increased Firmicutes/Bacteroidetes ratio or decreased Akkermansia muciniphila), drives low-grade systemic inflammation and insulin resistance through the translocation of bacterial lipopolysaccharides (LPS) into the bloodstream.

Maintain gut barrier integrity to prevent metabolic inflammation. This involves avoiding factors that cause dysbiosis (like excessive antibiotics or poor diet) and supporting beneficial bacteria (like Akkermansia muciniphila) which are often depleted in obesity and diabetes.

Substituting 5% of energy from carbohydrates or fat with protein increases the risk of type 2 diabetes by approximately 30%, regardless of whether the displaced macronutrient is fat or carbs.

If you are trying to prevent diabetes, simply swapping carbohydrates for protein (e.g., eating more meat instead of bread) may actually increase your risk. The study suggests that the increase in protein itself, rather than the decrease in carbs or fat, drives this risk. Balance your protein intake rather than maximizing it at the expense of other macros.

Caloric restriction (CR) reprograms the single-cell transcriptional landscape of aging, altering gene expression patterns in specific tissues.

Caloric restriction changes how genes are expressed in cells, particularly in rats. This database allows researchers to see exactly which genes are affected, potentially leading to drugs that mimic these benefits without strict dieting.

The association between egg consumption and CVD/mortality is largely explained by the dietary cholesterol content within the eggs, as the association becomes non-significant when adjusting for total dietary cholesterol.

If you eat eggs, be mindful of your total dietary cholesterol intake. The risk associated with eggs appears to come from their cholesterol content, so balancing egg intake with other cholesterol-containing foods is key to managing CVD risk.

Enhancing autophagy through genetic or pharmacological means improves glucose tolerance, insulin sensitivity, and resistance to obesity in high-fat diet models.

Boosting your body's natural cleanup processes (autophagy) can help you stay lean and sensitive to insulin, even if you eat a high-fat diet. This suggests that maintaining cellular health through fasting or exercise is as important as the food you eat.