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
Wolf were suggesting metformin as a general all-purpose health
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
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,
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
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
On Disruption Of the Food Industry Being Hard or
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
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.
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
As always, thanks for reading.
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among people with type 2 diabetes. Diabetes Care.
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.
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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.
Dear Mark: Metformin Side Effects, Kraft Heinz Deal Questions
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