by Tanya Zilberter, PhD
It’s no surprise that different foods influence insulin release differently. But how, exactly? Which food components called macro-nutrients are pro-insulin and which are anti-insulin?
The Wilder’s Formula
In 1920s, neurologists were desperate to find an alternative to existing antiepileptic drugs to control the drug-resistant form of childhood seizures. They found that making the brain to run on ketone bodies instead of glucose (which is normally the brain’s fuel of choice) reduces or completely stops the seizures in up to 90% of children with intractable epilepsy.
At the Mayo Clinic in 1921, Dr. R.M. Wilder created a diet that was designed to mimic the biochemical changes occurring during fasting when the preferred carbohydrate biochemical pathway is being switched to lipid pathway using body’s own fat for fuel. The clinical ketogenic diet was born.
Since that time, clinical dietitians used the Wilder formula describing (in the terms of ketosis) the interplay of insulin and its antagonist glucagon. The ratio determines how “ketogenic” the diet is - the higher the ratio, the more ketogenic the diet — and the more “anti-insulin” it is. With the Metabolic Syndrome in mind, it’s convenient to use the terms: “anti-insulin” (AI) instead of “ketogenic” and “pro-insulin” (PI) instead of anti-ketogenic. Then the formula will be read as the following:
AI : PI = (0.9 fat plus 0.46 protein) : (1.0 carb plus 0.1 fat plus 0.54 protein)
The numbers preceding the nutrient names are coefficients that are calculated basing on the nutrient’s ability to cause or to oppose the release of insulin.
• Carbohydrate is assigned the coefficient 1.0 because it is an absolute pro-insulin nutrient. The more carbohydrate grams a food contains, the more insulin release it causes.
• Fat is a 90-percent anti-insulin nutrient because it is only 10-percent efficient in releasing insulin.
• Protein is something in-between. For every 1 gram of protein consumed, roughly 1/2 gram will be converted into glucose, thus raising insulin levels.
However, the 1/2 gram of consumed protein will also stimulate the release of insulin-opposing hormone glucagon, thus acting as an anti-insulin nutrient.
Of course, for the metabolic syndrome management, the higher the AI : PI ratio, the better. But how high should it go?
I found it convenient to introduce an “Anti-insulin Index” (or AII) to make it easier to use, so instead of talking about AI : PI ratio of, for example, 5:1 or 0.5:1, let’s use AII of 5 or 0.5.
Typical ketogenic (anti-insulin) diets operate in the range of AI : PI from 2:1 to 5:1 so the AII for them would be between 2 and 5. Below AII=2, it is difficult to achieve sufficient insulin suppression.
However, experiments showed that as the AII increased, even in the range from 0.5 to 1.0 to 1.5, the lipolysis rate also increases.
Lipolysis Rate Increases With the Increase of the Anti-insulin Index

This fact is illustrated by the chart on the top right. It’s based on the data describing how with the increase of fat content of a diet, fat burning rate also increases. Since the exact macronutrient content and the fat burning rate figures were available in the article, I’ve been able to calculate the AII of all three diet versions. Diets were the same in calories and protein but different in fat and carbs.Needless to mention is the fact that a higher lipolysis rate corresponding to higher AII directly relates to one of the potent approaches to Metabolic Syndrome management, weight loss or, to put it more precisely, fat loss.
Yellow squares: Lipolysis rate (fat milligrams burnt by 1 kg of body weight in 1 minute). Purple squares: Anti-insulin Index
Sources:Wilder RM. The effect of ketonemia on the course of epilepsy. Mayo Clin Bulletin, 1921;2:307-308
Am J Physiol; Endocrinol Metab 280: E391-E398, 2001; 0193-1849/01