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.