Paleo Diet Drug Interactions, Uses, Effectiveness, Safety & More
What is this page for?
First and foremost: how Paleo Diet interacts with medications. The heart of this page is the interaction list — every drug Paleo Diet is known to interact with, and how serious each one is.
But these pages have grown well beyond that into a full monograph — what Paleo Diet is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy
Check Paleo Diet against your medication
Add one medicationDrugs that interact with Paleo Diet
0 medications have a known interaction with Paleo Diet, graded by severity. Select any drug for the full evidence-based detail.
We don’t currently list any known drug interactions for Paleo Diet. This doesn’t guarantee none exist — always confirm with your pharmacist before combining supplements with your medications.
What Severity, Likelihood & Evidence Mean
Severity — How Serious It Can Be
- Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
- Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
- Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
- No known interaction. Checked against our sources with nothing documented — not the same as proven safety.
Likelihood — How Well It’s Documented
- Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
- Probable. Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
- Possible. Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
- Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Where This Data Comes From
- Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
- Each drug listed above links to the full report for that exact Paleo Diet combination — clinical detail, likelihood, evidence level, and citations.
- Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.
Paleo Diet: Uses, Safety & Side Effects
The Paleo diet is an eating pattern based on whole, minimally processed foods thought to resemble what early humans ate, while avoiding grains, legumes, dairy, and added sugar. Short-term studies suggest it may help with weight loss and some heart and blood-sugar markers, but long-term safety and benefits are not well proven. Talk with your doctor or a dietitian before making big diet changes, especially if you have a health condition.
- Common forms
- Whole-food eating pattern (meats, fish, eggs, vegetables, fruits, nuts, and seeds)
- Weight loss
- Better blood sugar control
- Heart health
- Reducing processed-food intake
- General wellness and energy
Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.
Generally safe for healthy adults short-term, but it can be restrictive and may miss some nutrients.
Insufficient reliable information available; avoid use.
Read the full pregnancy detailInsufficient reliable information available; avoid use.
Read the full breastfeeding detailPregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.
Overview
The Paleo diet, sometimes called the "caveman" or "Stone Age" diet, is an eating pattern rather than a supplement or herb. It is built around foods that early humans might have eaten before modern farming, such as meat, fish, eggs, vegetables, fruits, nuts, and seeds.
The diet leaves out foods that became common after farming and food processing began. This usually means no grains (like wheat, rice, and oats), no legumes (like beans, lentils, and peanuts), no dairy, and no added sugar or highly processed foods.
People follow the Paleo diet for many reasons, including weight loss, eating fewer processed foods, and trying to feel more energetic. There are many versions, and some people are stricter than others.
How it works
The main idea behind the Paleo diet is that the human body may be better suited to whole, unprocessed foods than to many modern processed foods, refined grains, and added sugars.
By cutting out processed foods and sugar, people often eat fewer empty calories and more protein, fiber from vegetables and fruit, and healthy fats. This can help with feeling full, eating less overall, and steadier blood sugar.
These explanations are reasonable, but they are partly based on theory and short-term research. The diet is not a single active compound, so its effects depend on the overall mix of foods a person eats and what they replace.
Does Paleo Diet work?
How to read these evidence grades
Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.
Possibly Effective Obesity
Although following the paleo diet reduces weight, there is no evidence that it is better than other reduced calorie diets. Two small preliminary studies show that following the paleo diet for 3-5 weeks reduces weight by 2.3 kg in healthy volunteers and 4.5 kg in overweight postmenopausal healthy women when compared to baseline. One small clinical study shows that following the paleo diet for 6 weeks reduces weight by 3.7 kg, reduces waist size, and improves satiety in overweight men with ischemic heart disease when compared to baseline. These outcomes were comparable to following a Mediterranean-like diet. Other preliminary clinical research in overweight postmenopausal women shows that weight loss with the paleo diet is 4-5 kg greater than with a low-fat diet at 6, 12, and 18 months, but not at 24 months .
Also studied for 6 conditions — evidence insufficient to rate
Insufficient Reliable Evidence To Rate Cardiovascular disease (CVD)
A meta-analysis of eight small clinical trials shows that following the paleo diet for up to 180 days might improve some risk factors for CVD. In the pooled analysis, the paleo diet was associated with reductions of 1.7 kg in body weight, 1.3% in body fat percentage, 4.8 and 3.2 mmHg in systolic and diastolic blood pressure, respectively, 9 mg/dL in total cholesterol, 5 mg/dL in low-density lipoprotein (LDL) cholesterol, and 27 mg/dL in triglycerides, as well as an increase of 2 mg/dL in high density lipoprotein (HDL) cholesterol, when compared with other diets. However, the generalizability of these results is unclear as the patient populations, comparator diets, and study durations varied widely across the included studies.
Insufficient Reliable Evidence To Rate Diabetes
A meta-analysis of four small clinical trials shows that following the paleo diet for up to 12 weeks does not seem to improve plasma glucose, glycated hemoglobin (HbA1c), insulin, or insulin resistance when compared with other healthy diets. However, there are significant limitations with this analysis. Only two of the studies lasted longer than 3 weeks, and the comparator diets varied across studies. Additionally, only two of the studies included patients diagnosed with type 2 diabetes. One of these studies, which enrolled patients with diabetes or glucose intolerance and ischemic heart disease, shows that following the paleo diet for 12 weeks decreases plasma glucose levels when compared with following a Mediterranean-like diet. The other study, which enrolled patients with well-controlled type 2 diabetes, shows that following the paleo diet for 3 months decreases HbA1c levels, but does not affect response to glucose tolerance tests, when compared to baseline. The validity of these findings is limited by the lack of a comparator group.
Insufficient Reliable Evidence To Rate Gingivitis
Preliminary clinical research shows that following the paleo diet for 4 weeks increases bacterial count and plaque levels and decreases bleeding on probing in healthy subjects without access to standard oral hygiene.
Insufficient Reliable Evidence To Rate Hypercholesterolemia
A small clinical study in adults with hypercholesterolemia shows that following the paleo diet for 4 months lowers total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, and increases high-density lipoprotein cholesterol levels, when compared to baseline or to following the traditional heart-healthy diet. It is unknown if these effects are maintained long-term.
Insufficient Reliable Evidence To Rate Metabolic syndrome
A meta-analysis of 4 preliminary clinical studies assessing risk factors of metabolic syndrome shows that following the paleo diet seems to slightly reduce waist circumference and triglycerides, but not blood pressure or fasting blood glucose, when compared with baseline. This analysis has been criticized for over-exaggerating clinically insignificant results and using incorrect methods to pool data. Another meta-analysis of 10 clinical studies in patients with metabolic disorders shows that following the paleo diet has variable effects on measures of glycemic control and lipids.
Insufficient Reliable Evidence To Rate Multiple sclerosis-related fatigue
Preliminary clinical research in patients with multiple sclerosis shows that following the paleo diet for 12 weeks reduces fatigue scores when compared to baseline. Control patients following their regular diet saw non-significant increases in fatigue scores during the same time frame.
Source & disclaimer. Effectiveness ratings and evidence summaries are provided by Natural Medicines (Therapeutic Research Center) and shown as licensed. Where Natural Medicines hasn’t rated a use, HelloPharmacist’s pharmacists may add their own reviewed rating and evidence (each such entry is labeled). This is educational information, not medical advice — talk with your pharmacist or doctor before starting, stopping, or changing a supplement.
Safety & precautions
For most healthy adults, the Paleo diet is generally safe to try for a short time. Because it removes whole food groups, it can be low in some nutrients, especially calcium and vitamin D (from cutting out dairy) and fiber and certain B vitamins (from cutting out grains and legumes).
People with kidney disease, heart disease, diabetes, or those who eat a lot of red meat should be careful, since high intake of certain meats and fats may not be right for everyone. Anyone with a medical condition should talk with a doctor or dietitian first.
Pregnancy and breastfeeding: Nutrient needs are higher during these times, and a restrictive diet could fall short on calcium, vitamin D, folate, and other important nutrients. If you are pregnant or breastfeeding, do not start a restrictive diet without medical guidance.
Side effects
Common early side effects when starting the Paleo diet can include tiredness, headaches, irritability, and constipation or other digestive changes, especially in the first weeks as the body adjusts and as fiber sources change.
Over time, the main concern is missing certain nutrients, which can lead to problems like weak bones if calcium and vitamin D stay low. The diet can also be expensive and hard to stick with.
Serious problems are uncommon in healthy people, but anyone who feels very unwell, weak, or notices ongoing symptoms should stop and check with a healthcare provider.
Paleo Diet: Reported Adverse Effects
Documented safety reports on Paleo Diet from the evidence-graded Natural Medicines (TRC Healthcare) database, shown word-for-word from the licensed record.
Reports by conditionLactation Endocrine
In one case report, a breastfeeding woman reported to the emergency room with ketoacidosis after starting to follow the paleo diet. The ketoacidosis was attributed to the weight loss and carbohydrate deficit created by the diet in conjunction with the increased energy demands during lactation.
- Diamond, Evan, MD; Tibaldi, Joseph, MD. A case of ketoacidosis in a breastfeeding patient on the paleo diet. Endocrine Practice, suppl. Supplement 2; Jacksonville Vol. 22: 177.
Adverse-effects data: Natural Medicines, Therapeutic Research Center
Dosing
Because the Paleo diet is an eating pattern and not a supplement, there is no standard "dose." Instead, it is defined by which foods are included or avoided.
If you want to try it, focus on whole foods like vegetables, fruits, lean meats, fish, eggs, nuts, and seeds, and limit processed foods and added sugar. Many people do not need to follow every strict rule to gain benefit from eating fewer processed foods.
It is a good idea to work with a doctor or registered dietitian, who can help you plan balanced meals and decide whether a supplement (such as calcium or vitamin D) might be needed.
Paleo Diet & Pregnancy
Paleo Diet & Breastfeeding
© 2026 Therapeutic Research Center
Pregnancy & lactation ratings: Natural Medicines, Therapeutic Research Center
References & further reading
The 14 references that drive our Paleo Diet monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.
- Jonsson, T., Granfeldt, Y., Ahren, B., Branell, U. C., Palsson, G., Hansson, A., Soderstrom, M., and Lindeberg, S. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovasc
- Lindeberg, S., Jonsson, T., Granfeldt, Y., Borgstrand, E., Soffman, J., Sjostrom, K., and Ahren, B. A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease. Diabetologia 2007;50(9):179 PubMed
- Baumgartner, S., Imfeld, T., Schicht, O., Rath, C., Persson, R. E., and Persson, G. R. The impact of the stone age diet on gingival conditions in the absence of oral hygiene. J Periodontol 2009;80(5):759-768. PubMed
- Osterdahl, M., Kocturk, T., Koochek, A., and Wandell, P. E. Effects of a short-term intervention with a paleolithic diet in healthy volunteers. Eur J Clin Nutr 2008;62(5):682-685. PubMed
- Ryberg, M., Sandberg, S., Mellberg, C., Stegle, O., Lindahl, B., Larsson, C., Hauksson, J., and Olsson, T. A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women. J Intern Med 2013;274(1):67- PubMed
- Diamond, Evan, MD; Tibaldi, Joseph, MD. A case of ketoacidosis in a breastfeeding patient on the paleo diet. Endocrine Practice, suppl. Supplement 2; Jacksonville Vol. 22: 177.
- Fenton TR, Fenton CJ. Paleo diet still lacks evidence. Am J Clin Nutr. 2016;104(3):844. PubMed
- Manheimer EW, van Zuuren EJ, Fedorowicz Z, Pijl H. Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis. Am J Clin Nutr. 2015;102(4):922-32. PubMed
- Pastore RL, Brooks JT, Carbone JW. Paleolithic nutrition improves plasma lipid concentrations of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations. Nutr Res. 2015;35(6):474-9. PubMed
- Mellberg C, Sandberg S, Ryberg M, et al. Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: a 2-year randomized trial. Eur J Clin Nutr. 2014;68(3):350-7. PubMed
- Jamka M, Kulczynski B, Juruc A, Gramza-Michalowska A, Stokes CS, Walkowiak J. The effect of the paleolithic diet vs. healthy diets on glucose and insulin homeostasis: a systematic review and meta-analysis of randomized controlled trials. J Clin Med 2020;9 PubMed
- Lee JE, Titcomb TJ, Bisht B, Rubenstein LM, Louison R, Wahls TL. A modified MCT-based ketogenic diet increases plasma ß-hydroxybutyrate but has less effect on fatigue and quality of life in people with multiple sclerosis compared to a modified paleolithic
- Ghaedi E, Mohammadi M, Mohammadi H, et al. Effects of a paleolithic diet on cardiovascular disease risk factors: a systematic review and meta-analysis of randomized controlled trials [published correction appears in Adv Nutr 2020 Jul 1;11(4):1054]. Adv Nu PubMed
- Sohouli MH, Fatahi S, Lari A, et al. The effect of paleolithic diet on glucose metabolism and lipid profile among patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr 2021;1-12. PubMed
This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.
Parts of this content are provided by the Therapeutic Research Center, LLC.
DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.
© 2021 Therapeutic Research Center, LLC
Paleo Diet: Common Questions
What is Paleo Diet used for, and does it work?
Does Paleo Diet interact with prescription medications?
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What can I eat on the Paleo Diet?
Does the Paleo Diet help with weight loss?
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Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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