Dear Mark: Metformin Side Effects, Kraft Heinz Deal Questions

For today’s edition of Dear Mark, I’m answering a few questions from readers. First, the diabetes drug metformin looks like a “wonder” drug, even (or especially) for non-diabetics. Are there any known side effects? Is there anything we should watch out for?

Second, I address some of the concerns and criticisms shared in response to the Kraft Heinz announcement post.

Are there any adverse side effects to Metformin? It was mentioned in the fasting study.

Metformin is a diabetes drug that’s garnered a lot of attention from longevity seekers, health nuts, and low-carbers. I can see why. It appears to improve gut health (possibly because it impedes carbohydrate absorption, thereby increasing the amount of fuel available to our colonic bacteria), reduce cancer risk, lower blood glucose, improve insulin sensitivity, and increase fat loss. As far back as 2012, people I respect like Robb Wolf were suggesting metformin as a general all-purpose health enhancer.

Most of the interest in metformin from the general health crowd comes from its potential effect on longevity. It’s quite good at activating AMPK, the same pathway activated by exercise, fasting, and calorie restriction. There’s even some human research that hints at an effect—diabetics who take metformin actually live longer than non-diabetics who don’t take it. That’s a profound correlation.

But metformin does exert some of its effects via the hormetic pathway, which suggests it’s a stressor and may have a dark side. What could it be?

Well, there’s one main adverse side effect.

B12 depletion. Time and time again, studies show that metformin users are more likely to have B12 deficiency, whether they’re PCOS patients, Type 2 diabetes patients or others. Even when you age-match, health-match, and overall lifestyle-match your groups, the long-term metformin users have a higher chance of B12 deficiency. That certainly sounds causal, and even if it’s not, it’s a big risk. B12 plays a huge role in a host of physiological pathways. It protects against dementia, anxiety, depression, and fatigue. Its absence from vegan diets is one of the main reasons most vegans eventually flounder and have to turn to supplements or sneak into burger joints when no one’s watching. B12 is that important for overall health.

If you’re going to take metformin, make sure you’re tracking your B12 intake and status.

I’m not saying that’s the definitive answer. There may be more side effects. There probably are more. But on the whole, it’s a promising drug.

Now I’m going to address some of the concerns and questions from last week’s post on the Kraft Heinz acquisition. You guys made some good points and asked tough questions. I have answers.

On Disruption Of the Food Industry Being Hard or Impossible:

Believe me: We have disrupted the food industry. The ancestral movement is quite good at disruption. Take the fitness industry—just look at CrossFit and the thousands of small “functional fitness” gyms popping up everywhere. And the lighting industry—notice all the bulbs with warmer, less-blue lighting. And the tech industry—see the sudden development and adoption of “nightmode” to protect sleep and circadian health. Primal Kitchen disrupted the mayo, condiment, and dressing industry, not by upending or destroying it, but by highlighting the coming shift. That’s exactly why the acquisition occurred. They realized that things are changing and have changed, and that a growing number of people care about the quality of their packaged food and are willing to pay for it.

One thing that I didn’t realize until I got into this business—the packaged food business—is that smaller companies all eventually butt up against a ceiling. At some point, the smaller guys simply don’t have access to the same avenues of distribution as the larger guys. This isn’t negotiable. If you want to expand, you need access. From the beginning I wanted to put high-quality mayo, condiments, and dressings—the “extra” stuff that provides much of the added fat and sugar in the Western diet—in millions of homes. I couldn’t do that without access to those distribution channels, those industry connections, that capital. Now I can.

Some Worried About the Quality Of the Product. Will It Change?

I was adamant about maintaining product quality and integrity from the earliest of discussions with Kraft Heinz, and they were fully aligned with this from the beginning. It’s clear to me that Kraft Heinz sees that increasing numbers of people are flipping mayo jars around and scanning the labels. They know that the folks who buy Primal Kitchen products do so only because the ingredients we use are the best around, the very same ingredients you’d use if you were making mayo or dressing at home. If those ingredients change, you will stop buying. Business 101.

I know that. Kraft Heinz knows that.

On Extreme Skepticism:

We all have choices: do we let life unfold before us and respond accordingly, or do we fall prey to cynicism and assume the worst? I strongly recommend not being a cynic. It keeps many of us from ever fulfilling our potential and achieving our goals and dreams.

When I started Primal Nutrition, I left a well-paid, stable gig and put all my (borrowed) money and energy into the new venture. I had a wife and two small children at home, and the future was uncertain. It could have gone very wrong. But I did it just the same, because on some level I knew it would work. I left security and comfort and a steady paycheck for struggle and nerves and anxiety. My goal of changing how people eat and thrive kept increasing, from a million people, to ten million to a hundred million (I always think big). Now, with the leverage that Kraft Heinz brings, that goal of bringing healthier options to everyone is within reach.

On the Opportunity At Hand:

All across the U.S., in small towns and metropolises, rural communities and suburban sprawl, the vast majority of people are still eating way more seed oil and shifting the fatty acid ratio of their tissues accordingly than humans have ever done.  I think of all the people dousing the salad their doctor said they should start eating in soybean oil-based dressing and buying “olive oil mayo” that was mostly just seed oil, and it frustrates me. Imagine if they switched? Imagine if they all switched? Imagine if we were able to shift the collective omega-6:omega-3 ratio back toward ancestral optimums. Longtime readers know how big a change a person can make in his or her health just by changing the fats you eat. Now imagine a population doing it.

It could be big.

That’s it for today, folks. Take care and share your thoughts below.

As always, thanks for reading.


Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009;32(9):1620-5.

Bannister CA, Holden SE, Jenkins-jones S, et al. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes Metab. 2014;16(11):1165-73.

De haes W, Frooninckx L, Van assche R, et al. Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2. Proc Natl Acad Sci USA. 2014;111(24):E2501-9.

Esmaeilzadeh S, Gholinezhad-chari M, Ghadimi R. The Effect of Metformin Treatment on the Serum Levels of Homocysteine, Folic Acid, and Vitamin B12 in Patients with Polycystic Ovary Syndrome. J Hum Reprod Sci. 2017;10(2):95-101.

Pongchaidecha M, Srikusalanukul V, Chattananon A, Tanjariyaporn S. Effect of metformin on plasma homocysteine, vitamin B12 and folic acid: a cross-sectional study in patients with type 2 diabetes mellitus. J Med Assoc Thai. 2004;87(7):780-7.

TAGS:  dear mark

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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64 thoughts on “Dear Mark: Metformin Side Effects, Kraft Heinz Deal Questions”

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  1. Can you take metformin if your blood sugar is normal or if you’re fasting? I would think that would push it too low.

    1. Metformin does not induce hypoglycemia as it’s mechanism of action is decreasing hepatic glucose production and absorption of glucose in the intestines as well as increasing insulin sensitivity. It does not cause an increase in insulin production (like some of the other diabetes medications), which would predispose an individual to hypoglycemia. Hope that helps.

  2. Mark, I must admit I reacted rather cynically when the Kraft Heinz news first broke, but you have put my mind at ease with this post. I can see now why this is a win for the ancestral health community and the whole country in general.

    Hopefully this is all part of a larger shift….
    Great post Mark

  3. Mark…. I continue to be impressed by your positive foresight and optimism. Things don’t change without dreams, visions, ideas, and teamwork. I am confident that the merger will add momentum to the ancestral health movement, and is a good step toward greater change.

  4. One more question. I prefer berberine to metformin for my diabetic blood sugar control. Does metformin have similar longevity benefits?

  5. Regarding the Kraft deal. Can we please not let perfect be the enemy of the good. Now primal products will find their way into more homes across the land which is a step in the right direction.

    1. Not just across the land (America) but hopefully overseas as well. Hopefully we’ll get these products in Australia. I’ve been making my own mayonnaise but it would be wonderful to try different flavours and also to encourage my friends and relatives to switch over.

      1. I’ll second that. It would be great to be able get this in Australia. Making up olive oil vinegarette’s easy enough (just put the ingredients in the jar and shake and put the jar in the refrigerator and use as needed) but the other stuff can be quite involved and a real PITA if you’re short on time.

        1. You can order Primal Kitchen mayo on iherb and they’ll ship to Australia. I’m in Sydney and have been doing getting it for some time. Hopefully the range available will increase with this partnership ??

      2. I second that, too. I absolutely love that Mark has gotten the recognition he so deserves. Hopefully, we will be seeing Primal Kitchen in Europe soon!

  6. Hi Mark,
    I’m excited for your vision and I’ve had faith in you from the beginning, back when I found your blog in 2012. I appreciate the depth and accuracy of the content as well as how accessible you are. It was truly a blessing when you started Primal Kitchen. However, I’ve never had any faith in the food industry to do the right thing. I think that if anyone can disrupt the system and shift the paradigm it will be you. I hope it’s as big as you dream it will be, and I’ll keep my fingers crossed and dream with you. Thanks for reading. Jen

    1. I agree, but am super-worried about Big Food lying about the oil they use, etc., the way so many lie about 100% olive oil. It’s been so great to have some trusted products to save a bit of time, but now I am very worried.

  7. Great jumping off point (hopefully) to go from primal condiments, to taking over 1/2 a grocery stores unhealthy choices. I bet you could walk down any isle with a notepad and fix a great percentage of that foodstuff. Great start Mark. Congrats again.

  8. You are right to do this. Iwe e out here in Average Food Land will benefit and hopefully you will as well.

  9. I loved being on Metformin but my doctors actually care about side effects of medications. My primary care doc was concerned that Metformin was hurting my (weak) kidneys.

  10. Metformin wouldn’t be good for folks with histamine intolerance or mast cell disorder like me. I think it’s poison, longevity buffs might think it’s great but then weight lifters think anabolic steroids and extreme weight lifting are great until they stroke out. No thanks to either, primal/paleo diet is my best medicine.

  11. Hi Mark, Your honesty about the Kraft Heinz scenario is both refreshing and appreciated. Down under in Australia, I hope to be able to see your PK products on the shelfs so I can buy it.
    Keep it Mark, your doing wonders. 🙂

  12. Thank you for mentioning those outlying small towns and rural areas. Their food choices can be very limited due to lack of access to wider distribution of better options like PK. Thank you for choosing the greater good.

  13. Mark, thank you for addressing the comments regarding the KraftHeinz deal. It is encouraging that you take the concerns of your followers seriously, and your point on cynicism is well taken. I hope to see more of your products around in the future.

  14. love PK mayo! can’t wait to try the other products! way too go mark! look forward to hopefully seeing these in my neck o’ the woods

  15. Well done Mark. Congrats on a well deserved product deal. Looking forward to seeing the product on Canadian shelves (hopefully eye level) later in 2019.

    It’s a win for the ancestral movement and I look forward to your ongoing research and the sharing of best practices among the community on this site and events like Paleo FX.

    Continued success. Hope you found a good spot to SUP and plugged into an Ultimate Group in Miami.


  16. Can you make a Mayo with metformin and increased B12? Thaanks

  17. I recently read a PubMed article that possibly ties Metformin use in diabetic patients with MTHFR mutation (in particular C677T) causing Vitamin B12 deficiency leading to Hyperhomocysteinemia which then may increase risk of vascular thrombosis. I have also read many articles/opinions that convey there is nothing to worry about with MTHFR mutations. My Mom is a Metformin treated (several years) diabetic who has the C677T mutation and has had one blood clot in her leg and, now while on blood thinners, has been experiencing severe swelling in lower extremities. I’m trying to figure out if we should be looking into this combination of Metformin and MTHFR mutation as the cause behind this or if the docs will think I’m just another wack-a-doo who diagnoses things via the internet, especially since I’ve already self-diagnosed Hereditary Hemochromatosis in myself earlier this year! Genes are fascinating! 🙂

    1. I have been taking care of diabetics in my family for years..(my parents were insulin dependent) and now my husband. if we could afford it I would take him to a functional Dr.(you can find them through the institute of functional medicine) they work with you getting to the cause of the problem rather then just treating the symptoms. Dr. Mark Hyman (who is a functional dr. based in Missouri) wrote a book The Blood Sugar Solution Cookbook, that has saved my life in learning how to care for my diabetic loved ones. Maybe it could help you too.

  18. Thank you Mark. Thank you for not being cynical of Kraft Heinz intentions. Thank you for believing the best. Thank you for holding true to your beliefs and standards. Thank you for fighting the good fight. Good things do happen to good people. As a Primal Health Coach I am thrilled that it’s going to be easier for my clients to get Primal Kitchen products. I wish you nothing but prosperity because if you prosper we all prosper

  19. Thanks Mark, for your openness and honesty, for your vision, your can-do attitude, and for taking us on the journey with you! Looking forward to hopefully getting some PK products here in Toronto!

    1. Grace, for you and other Canadians out there, if you are not familiar with Natura Market, check it out. They carry many, but not all, PK products and deliver for free with a relatively small order.

  20. Go, Mark, go! Get those Primal products even more into the mainstream!

  21. This news took me by surprise, being a Primal Health Coach myself and having my everyday job working at a Kraft-Heinz plant to support my family I now feel more involved. I currently work for the biggest Philadelphia Cream Cheese plant in the U.S. in a small farm town in upstate NY. I can attest that Kraft-Heinz does have pretty strict quality and ingredient standards, especially at our plant after switching out brick cream cheese over to only 5 ingredients. The plant has also done a lot to create a large amount of well paying jobs for people in an area that doesn’t have much else to offer, and it has done a huge part in supporting local farms, as we get milk from smaller farms and bigger farms in the area. I hope this deal works out in a way that maintains the quality of the product while making it more accessible to everyone.

  22. Metformin requires a prescription. I have not found a doctor willing to prescribe it off label as I am not diabetic.

  23. Whatever happened to the Primal Kitchen restaurant franchise?

    1. The Indiana one made it about 7 months. Culver City even less time I believe. Roseville never opened. I heard there was one in Santa Cruz as well. The website is gone, domain is available, it’s like the whole thing was erased. I was skeptical from the start…restaurants are the highest risk business there is with tremendous failure rates. Hopefully the franchisees didn’t take it on the chin too badly, but they had to have lost a tidy sum.

      1. I believe I read somewhere that the issue was at the partner/business arrangement level, not the restaurants themselves.

      2. If you’re interested, Mark talks a bit about it on Brad Kearn’s podcast, Get Over Yourself.

  24. Just pointing out, the citations include info supported by some of the following groups: Tenova, AstraZeneca, Bristol Myers, etc., and Andy Dilllin, (the editor, whose name is sooo long that they abbreviated it to A.D.) is probably Andy Dillin whose lab is supported by Teva Pharma, American Heart Association (proud supporter of the low fat ideology), America Diabetes (proud supporter of health grain eating), Burroughs Wellcome, Dana Runyon, yadda yadda yadda.
    Combine that with the knowledge of rampant cherry picking in medical research publication and clinical trial reporting, and that both big ag and big pharma are supported by big chemical in their supply chain, and I’d say there’s a lot more we don’t know about metformin than what we do know. Of course there’s no need to point any of that out to the educated readers on this blog, right?

    1. Metformin has generated quite a bit of interest by the life extension crowd and a large scale study of its potential efficacy for people is set to begin soon. It appears to address many of the scourges of aging. I am for the most part anti-pharmaceutical, but this seems like one drug that MAY have promise. If I was to take it I would definitely increase my B12 levels and have kidney and liver blood testing done regularly. Metformin has been around since the 1950’s so it does have a track record which overall appears to be positive. That “said”, I am still not ready to ask my allopathic doctor to give me a prescription for it at this point in time.

    2. lol….Good for you Jeb. I was thinking the same thing! I mean really? B12 deficiency? that’s all ya got?

    1. Great minds think alike, Josh. Look for it on Friday’s Link Love. I might do something on it beyond that, too. Thanks for sharing it here. Good stuff. — M

  25. Are people in those limited food communities really going to shell out +$10 for a small jar of mayonnaise?
    Or is the price coming down?

    Whatever it is, I guess time will tell.

  26. As a Critical Care Paramedic it has always seemed that Metformin has been a wonder drug for diabetics. Is it good for those looking to control blood sugar levels? It appeas so, with an anti cancer spin too. I now take a low dose daily and my Dr descibes my bloodwork as ” posterboy “good.

  27. As a long time executive in the food industry I can’t help but hearing The Doors song “This is the end”. It was a lot of money. I don’t blame you & good for you. Within a year or two the integration of your product line into the mainstream will start. That’s just how it goes.

  28. Quick one Mark. Does the acquisition mean your products may come to Australia?! That would be great. Cheers, Tom

  29. Regarding Metformin. My daughter who lives with Cognitive Impairment was diagnosed with PCOS and prescribed Metformin. I gave it to her for maybe a year. Every morning, she would throw up. It just made her so sick. Finally, I said “enough”. Metformin not for everyone. On Heinz, Bravo Primal Nutrition! It’s about time someone started making some validly healthy inroads into the vast wastelands of the supermarkets. I’m in!!

  30. Mark – I’m curious how you ensure the authenticity of the ingredients used in Primal Kitchen products, especially those higher-value ones that may be prone to substitution (olive oil, spices, cocoa, etc.) Thank you!

    1. Karen, thanks for your question. We have supplier standards that must be met, including ingredient authenticity, an array of testing, and 3rd party supplier audits. Suppliers must meet FDA standards for pure, safe food that is not adulterated. We are mindful of country of origin when sourcing ingredients as well. For example, ingredients such as avocado oil are regularly tested for identity authenticity. The cocoa in the Chocolate Collagen Fuel is tested for identity authenticity upon receipt from the supplier. Best — M

  31. It’s refreshing, but disappointing at the same time, that only J. Siegel had the guts to say “the emperor has no clothes.” This is a betrayal of the people that supported Mark & his primal products because as J points out, it is only a matter of time before Kraft Heinz begins using cheaper ingredients to maximize profits. As Mark wrote, that’s Business 101.

    1. Tom, everyone is entitled to their thoughts here. I stand by what I wrote, and I do want to correct something you attribute to me in your comment. I noted that keeping the ingredients the same was in the agreement. I know if the ingredients change, you (current customers) won’t buy the products. That decision (to not buy) is what I was referring to as Business 101.

  32. Actually, I’m quite happy about the Kraft-Heinz acquisition because I live in Asia for work and load up on dressings whenever back in the US. Ideally, Kraft starts distribution out here, so I can put an end to the schlepping bottles of salad dressing and questioning looks from TSA.

  33. Anyone newly diagnosed with Diabetes Type II should investigate Berberine. It is natural, not chemical, has the same results, & NO side effects. Another article explaining how/why to take Berberine instead of Metformin. Big Pharma doesn’t own all the places that grow the plants, so they don’t make money off it, so therefore, no big trials or publicity. My blood sugar was under control within 8 weeks. Do your own research and then decide what to do.

  34. Knowing you Mark, I bet your restless and creative mind must be planning something new for us now that a beautiful chapter of your life has been concluded. What’s coming buddy?

    1. Thanks, Rafael! I’ve got lots in the works, including some new product launches and a new book on longevity that’s due out next October. More to come, and as always I’ll share it with the tribe here first. Best — M

  35. As for the Mayo…hiepfully they will lower the production costs and therefore the retail price. Lets hope they dont get Krafty and call it something dumb, like artisanal and jack up the price.

    Second, lets hope they stabilize the product better. Cant tell you how many jars of Primal mayo went bad on me. They just dried up in under 4 weeks time. (I dont eat a lot of mayo dishes, nor can I force myself to, in order to go thru the jar in a week) Had to toss them out. Thankfully I only bought the stuff on sale at Whole Foods. But still…waste of food.

    Third. Manufacturers are allowed to not list certain ingredients when they arat e low levels…like Carrageenan, in dairy foods. So lets hope thats not an issue with Kraft Heinz.

    1. I also don’t use lots of mayo, once every couple weeks maybe, and I’ve bought several jars of Primal Mayo since it hit the market, online and in stores. It’s never dried out. Are you putting the lid back on it?

  36. My husband has been on metformin for a couple of years and recently his Dr. put him on blood pressure meds as a direct result of metformin use . . .my thoughts have always been that diabetes is one of the most curable if not manageable diseases without medication…if the recipients are just willing to do what it takes to get there. Apparently our insurance co asked my husbands Dr. why he had not started the blood pressure meds earlier as this outcome was expected. My husband realized the side effect was fended off because he was also taking Immunocal a whey protein isolate with bonded cysteine (a glutathione precursor) that boosts your immune system. he had stopped taking it because his order was delayed. I understand also that liver damage is a side effect of long term use. Medication has its place but if you can avoid it with proper diet and exercise…….you should

  37. During this festive season of giving, let us take time to slow down and enjoy the simple things. May this wonderful time of the year touch your heart in a special way. Wishing you much happiness not just today, but throughout the New Year.