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How HNF1A Affects Your Response to a Ketogenic Diet

The ketogenic diet is a high-fat, very low-carbohydrate approach that shifts the body from using glucose to using ketones for energy. This change can improve fat burning, reduce hunger, and stabilize energy for many people. The HNF1A gene is involved in how your liver and pancreas manage glucose and fats. Variants in this gene can influence insulin dynamics and fat metabolism and may change how effectively you respond to a ketogenic or low-carbohydrate, high-fat eating plan.

What this means for you

  • Some HNF1A variants are associated with a better weight-loss response on high-fat, low-carbohydrate diets.
  • Regardless of genotype, focusing on food quality, hydration, electrolytes, resistance training, sleep, and stress management improves results.
  • PlexusDx provides information about genetic predispositions. This content is educational and not medical advice. Always discuss changes to your diet, supplements, or medication with your healthcare provider.

Practical nutrition and lifestyle tips for people doing keto

  • Prioritize unsaturated fats: olive oil, avocados, olives, nuts, seeds, and fatty fish like salmon.
  • Keep protein moderate and evenly spaced throughout the day to support muscle and satiety.
  • Choose fiber-rich, non-starchy vegetables: leafy greens, broccoli, cauliflower, zucchini, and peppers.
  • Stay hydrated and replace electrolytes: sodium, potassium, and magnesium matter during adaptation.
  • Include resistance training 2 to 4 times per week to preserve lean mass and support metabolic health.
  • Prioritize 7 to 9 hours of quality sleep and use stress-management strategies such as mindfulness, deep breathing, or light activity.
  • Monitor how you feel, your energy, and body composition. Adjust carbohydrate timing, calorie intake, or fat levels as needed for sustainability.

Genetic interpretation for rs7957197 (HNF1A)

Two effect alleles (TT) — higher likelihood of greater weight loss on a high-fat diet

If your genotype is TT, research suggests you may experience a stronger weight-loss response when following a high-fat, low-carbohydrate or ketogenic diet. HNF1A influences how your liver and pancreas regulate glucose and fats. With TT, you may see improved insulin regulation and enhanced fat mobilization as the body shifts to fat-based energy.

How to optimize this response

  • Emphasize high-quality unsaturated fats: olive oil, avocado, macadamia and almonds, chia and flax seeds, and fatty fish.
  • Keep protein moderate: aim for 0.6 to 0.8 g per pound of body weight per day, spread across meals.
  • Load up on low-carb, fiber-rich vegetables for gut health and micronutrients.
  • Manage electrolytes — include sodium in cooking or broth, eat potassium-rich keto-friendly foods like avocado and spinach, and consider magnesium supplementation if you experience muscle cramps or poor sleep.
  • Combine keto with resistance training and include some high-intensity or interval-style cardio periodically to support fitness and insulin sensitivity.
  • Track energy levels and hunger. If you tolerate strict keto well, it may be a very effective tool for you; if not, consider cyclic or targeted carbohydrate approaches.
One effect allele (AT) — modest tendency toward better weight loss on keto

If your genotype is AT, you carry one copy of the effect allele that is associated with a tendency toward greater weight loss on high-fat, low-carbohydrate diets. Your HNF1A profile may support more favorable insulin dynamics and fat burning when carbohydrates are limited, which can lead to improved satiety and steadier energy.

How to optimize this response

  • Focus on unsaturated fats: extra virgin olive oil, avocados, walnuts, and fatty fish to encourage healthy lipid profiles.
  • Keep protein moderate and distribute it through the day to protect lean mass and appetite control.
  • Eat a wide variety of non-starchy vegetables to maintain fiber, vitamins, and minerals.
  • Maintain electrolyte balance: add a pinch of salt to meals if appropriate, include potassium-rich low-carb foods, and consider 200–400 mg elemental magnesium nightly if needed and approved by your provider.
  • Support adaptations with resistance training and adequate sleep to improve body composition and insulin sensitivity.
  • If you find strict keto challenging, a moderate low-carb plan with occasional carbohydrate refeeding around workouts can be effective.
No effect alleles (AA) — typical response to ketogenic diet

If your genotype is AA, you carry two copies of the non-effect allele and are likely to have a typical response to a ketogenic diet. You may not have the enhanced weight-loss effect seen with the other genotypes, but solid results are still achievable with careful food choices and consistent habits.

How to optimize your results

  • Prioritize food quality: unsaturated fats from olive oil, nuts, seeds, and fatty fish; moderate protein; abundant low-carb vegetables.
  • Consider a flexible approach: strict keto, moderate low-carb, or cyclical carbs around workouts, depending on preference and performance.
  • Focus on resistance training 2 to 4 times per week to preserve muscle and improve metabolic health.
  • Prioritize electrolytes during adaptation: sodium, potassium, and magnesium to reduce headaches, fatigue, and cramps.
  • Monitor biomarkers such as fasting glucose, HbA1c, lipid panel, and ketone levels if you are making major dietary changes or are on medications that affect glucose.
  • Iterate based on results. Sustainable habits, adherence, and food quality usually matter more than genotype for long-term success.

Supplements and tests to consider

  • Electrolyte support: sodium (salty broths), potassium-rich foods, and magnesium citrate or glycinate as tolerated.
  • Omega-3 fatty acids: fish oil or algae-based supplements for cardiovascular and inflammatory support, especially if you eat low amounts of fatty fish.
  • Vitamin D if levels are low; discuss testing with your healthcare provider.
  • Periodic blood tests: fasting glucose, HbA1c, comprehensive metabolic panel, lipid profile, and electrolytes if starting or intensifying a ketogenic plan or if you take glucose-affecting medications.

When to consult your healthcare provider

  • If you take diabetes medications, insulin, or medications that affect electrolyte balance.
  • If you have a history of high cholesterol, cardiovascular disease, pancreatitis, or liver or kidney disease.
  • If you experience persistent dizziness, fainting, irregular heartbeat, severe gastrointestinal symptoms, or other concerning changes after changing your diet.

PlexusDx provides educational information about how genetic variants like those in HNF1A may influence diet response. This information is not medical advice. Always consult with your healthcare provider before making changes to your diet, supplements, or medication based on genetic results.