The Paleo Diet: Principles, Benefits, Risks, and GLP-1 Medication Considerations

Curious about the Paleo diet and how it might interact with modern weight loss medications? Here’s what you need to know.

What Is the Paleo Diet?

The Paleo diet is a whole-food-based eating pattern modeled after foods presumed available to humans during the Paleolithic era (2.5 million to 10,000 years ago). It emphasizes:

• Lean meats, fish, vegetables, fruits, nuts, and seeds

• Excludes grains, legumes, dairy, refined sugars, and processed foods

Typical macronutrient ratios:

• 25–35% protein

• 30–40% fats

• 25–35% carbohydrates (primarily from non-starchy vegetables and low-sugar fruits)

Potential Benefits and Applications

Clinical studies suggest the Paleo diet may benefit:

• Weight Management: Higher protein intake increases satiety hormones like GLP-1, aiding appetite control.

• Type 2 Diabetes: A 2015 meta-analysis in the European Journal of Clinical Nutrition found greater improvements in waist circumference and lipid profiles compared to standard diets.

• Autoimmune Conditions: A 2019 Frontiers in Immunology pilot study noted reduced inflammatory markers in rheumatoid arthritis patients after 30 days.

• Irritable Bowel Syndrome (IBS): Elimination of fermentable carbohydrates (FODMAPs) in grains/legumes may reduce bloating and discomfort.

• Cardiovascular Health: Improved omega-3/6 ratios from grass-fed meats and wild seafood may lower triglycerides.

Combining the Paleo Diet with GLP-1 Medications

For individuals following the Paleo diet and taking GLP-1 receptor agonists (e.g., semaglutide, liraglutide), there are unique considerations to optimize health outcomes. These medications, often prescribed for weight loss or diabetes management, enhance satiety and regulate blood sugar levels. When paired with a Paleo eating pattern, careful planning is required to balance nutrient intake and manage potential side effects:

• Risk of Deficiencies: The Paleo diet excludes grains, legumes, and dairy—common sources of calcium, vitamin D, and certain B vitamins. GLP-1 medications can further reduce appetite, potentially leading to insufficient nutrient intake.

  • Solution: Prioritize nutrient-dense foods such as leafy greens (calcium), fatty fish (vitamin D), and organ meats (B vitamins). Consider supplements if recommended by a healthcare provider.

• Protein Intake for Satiety: The Paleo diet and GLP-1 medications emphasize satiety. High-protein foods like grass-fed meats, wild-caught fish, and eggs align well with this goal.

  • Tip: Start meals with protein to maximize satiety signals from GLP-1 medications and support muscle preservation during weight loss.

• Digestive Health: GLP-1 medications can cause nausea, bloating, or constipation. The high fiber content of the Paleo diet may help, but it should be introduced gradually.

  • Recommendation: Slowly incorporate non-starchy vegetables like zucchini and spinach to avoid overwhelming the digestive system. Stay hydrated and consider fermented foods like sauerkraut for gut health.

• Balancing Fats: The Paleo diet encourages healthy fats such as avocado oil and omega-3-rich seafood. While these fats support GLP-1 function, excessive saturated fats may hinder metabolic goals.

  • Guidance: Focus on monounsaturated fats (avocados, olive oil) and omega-3s (salmon) while moderating saturated fat intake from sources like coconut oil.

• Blood Sugar Stability: The Paleo diet naturally limits refined carbohydrates, which aligns well with the blood sugar-stabilizing effects of GLP-1 medications.

  • Advice: Choose low-glycemic fruits (berries, apples) and avoid overly processed "Paleo-friendly" snacks that may spike blood sugar.

• Sustainability: Both the Paleo diet and GLP-1 medications require a commitment for lasting results. Strict adherence to Paleo principles can be challenging over time.

• Flexibility: Consider a modified “Paleo Plus” approach by reintroducing nutrient-dense foods like fermented dairy or legumes if they are tolerated. Paleo Plus refers to a flexible version of Paleo that allows certain nutrient-rich foods (e.g., fermented dairy, legumes) for sustainability and nutritional adequacy.

Potential Risks and Considerations

Clinical studies suggest the Paleo diet may include the following considerations:

• Nutrient Gaps: Dairy exclusion may lead to 50% lower calcium intake than the RDA; strategic intake of bone broth or leafy greens is advised.

• Transition Effects: Some experience “low-carb flu” (fatigue, headaches) during the first 1–2 weeks.

• Sustainability: Strict avoidance of grains/legumes can challenge long-term adherence in modern food environments.

• Cost: Grass-fed meats and wild-caught fish are often 20–50% more expensive than conventional options.

Paleo-Friendly and Excluded Foods

• Protein

  Included Foods: Grass-fed meats (beef, bison, lamb), wild-caught seafood (salmon, mackerel, shrimp), free-range poultry and eggs

  Excluded Foods: Grains (wheat, rice, oats), legumes (beans, lentils, peanuts), dairy products

• Vegetables / Fruit

  Included Foods: Non-starchy vegetables (kale, broccoli, Brussels sprouts), low-sugar fruits (berries, apples, citrus)

  Excluded Foods: Processed sugars and oils

• Fats

  Included Foods: Avocados, avocado oil, coconut oil, nuts/seeds (almonds, walnuts, pumpkin seeds)

  Excluded Foods: Canola oil, corn oil, soybean oil, sunflower oil, safflower oil, cottonseed oil, grapeseed oil, rice bran oil, peanut oil, vegetable oil blends, margarine, shortening, partially hydrogenated oils, butter, cream, cheese, refined olive oil, refined coconut oil

A Day of Paleo Meals

Meal Examples

Breakfast

• Sweet potato hash with ground turkey and spinach

• Scrambled eggs with smoked salmon and asparagus

Lunch

• Grilled chicken salad with mixed greens, walnuts, and olive oil dressing

• Zucchini noodles with grass-fed meatballs and marinara

Dinner

• Herb-crusted salmon with roasted Brussels sprouts

• Bison steak with mashed cauliflower and sautéed greens

Snacks

• Kale chips with sea salt

• Apple slices with almond butter

Historical Context

First proposed in the 1970s by gastroenterologist Dr. Walter L. Voegtlin, the diet gained mainstream traction in 2002 with Dr. Loren Cordain’s book The Paleo Diet. Cordain’s research at Colorado State University analyzed 229 hunter-gatherer societies, concluding that pre-agricultural diets were higher in fiber, omega-3s, and micronutrients than modern diets.

Scientific Basis and Evolutionary Rationale

• Evolutionary Discordance: Human genetics have changed less than 2% since the Paleolithic era, while 70% of modern calories come from Neolithic foods (grains, dairy) introduced ~10,000 years ago.

• Anti-Nutrient Avoidance: Excludes lectins (in grains/legumes) that may increase intestinal permeability, a factor in autoimmune disorders.

• Optimal Fatty Acid Ratios: Wild game and seafood provide a 1:4 omega-3:6 ratio vs. 1:20 in grain-fed meats.

Leading Paleo Experts

• Dr. Loren Cordain: Published over 100 peer-reviewed papers; his 2002 clinical trial demonstrated Paleo’s superior satiety effects vs. Mediterranean diets.

• Robb Wolf: Biochemist and author of The Paleo Solution; specializes in using Paleo to manage autoimmune thyroid conditions.

• Dr. Terry Wahls: Clinical professor at the University of Iowa who reversed MS progression using a modified Paleo protocol.

• Mark Sisson: Author of The Primal Blueprint; advocates for an 80/20 approach to Paleo adherence.

Essential Paleo Cookbooks

• Nom Nom Paleo by Michelle Tam: 100+ family-friendly recipes with photo guides for kitchen novices.

• Practical Paleo by Diane Sanfilippo: Condition-specific 30-day meal plans for autoimmune and digestive issues.

• Well Fed by Melissa Joulwan: Meal-prepping strategies for busy professionals.

• The Paleo Diet Cookbook by Loren Cordain: Recipes aligned with Cordain’s original clinical research.

Short-Term vs. Long-Term Use

• Short-Term (1–3 months): Effective for weight loss resets, with studies showing 5–10% body weight reduction.

• Long-Term: Requires careful planning to avoid nutrient gaps. Many adopt a “Paleo Plus” approach, reintroducing fermented dairy (kefir) or white rice for athletes.

Conclusion

The Paleo diet offers a whole-food approach that may support metabolic health, especially when thoughtfully combined with GLP-1 medications. However, it’s important to plan carefully to avoid nutrient gaps and ensure long-term sustainability. Consult with a healthcare provider or registered dietitian before making significant dietary changes.

Have you tried the Paleo diet or GLP-1 medications? Share your experiences with us at hello@foodinformed.com

Resources:

1. European Journal of Clinical Nutrition: Metabolic and physiologic effects from consuming a hunter-gatherer (Paleolithic)-type diet in type 2 diabetes

2. Nutrients: Paleolithic Diet—Effect on the Health Status and Performance of Athletes

3. American Journal of Clinical Nutrition: Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis

4. Healthline: GLP-1 Diet

5. Center for Science in the Public Interest (CSPI): Taking GLP-1 Obesity Drugs: What to Eat or Avoid