For today’s edition of
Dear Mark, I’m answering a bunch of questions from comment
sections. First, did I get AMPK and mTOR mixed up in a recent post?
Yes. Second, I give a warning for those who wish to add ginger to
their broth. Third, is it a problem that we can’t accurately
measure autophagy? Fourth, how does coffee with coconut oil affect
a fast? Fifth, is there a way to make mayonnaise with extra B12 and
metformin? Actually, kinda. Sixth, should you feel awkward about
proposing hypotheses or presenting scientific evidence to your
Great article, but a couple of amends are required with regards
to mTOR. Firstly, you mention in the last paragraph that curcumin
activates autophagy by activating mTOR. Reading the actual article
abstract though, it states the opposite, ie the effect of curcumin
“downregulating AKT/mTOR signaling pathway in human melanoma
Great catch. I’m not sure how I flipped that around. AMPK
triggers autophagy, mTOR inhibits it.
What you say about curcumin goes for all the other broth
ingredients I mentioned. Ginger, green tea, and curcumin all
contain phytonutrients which trigger AMPK, which should induce
autophagy, or at least get out of its way. What remains to be seen
is whether the amino acids in broth are sufficient to inhibit
fasting-and-phytonutrient-induced autophagy. I lean toward
“yes,” but is it an on-off switch, or is autophagy a spectrum?
Does inhibition imply complete nullification? I doubt it.
Regarding autophagy and health and longevity, it’s important
to note the manner in which glycine, the primary amino acid found
in broth and gelatin, opposes the effects of methionine, the
primary amino acid found in muscle meat and a great stimulator of
study found that while restricting dietary methionine increased
the lifespan of lab rodents, if you added dietary glycine, you
could keep methionine in the diet and maintain the longevity
benefits. That doesn’t necessarily speak to the effect of broth
on autophagy during a fast, but it’s a good reminder that broth
is a general good guy in the fight for healthy longevity.
Funny you mentioned ginger and turmeric as I add both, along
with a whole lemon and/or lime, to my list of ingredients when
cooking my broth. Here’s another great tip: I juice turmeric
root, ginger & lemon together in my Omega juicer and freeze in
ice cube trays. I add a cube to curries and other dishes.
That’s a great idea. One cautionary note about the raw ginger:
it will destroy your gelatin.
Raw ginger has a powerful protease, an enzyme that breaks down
protein. If you grate a bunch of ginger into a batch of finished
broth, or juice a few inches and dump it in, there’s a good
chance you’ll lose the gel. The amino acids will remain, but
you’ll miss out on the texture, the mouthfeel, the culinary
benefits of a good strong gelatinous bone broth.
Heating the ginger with the broth as it cooks, or even just
reducing the amount of raw ginger you add, should reduce the
“Bone broth with turmeric, green tea, and ginger might
actually combine to form a decent autophagy-preserving drink during
a fast. Only one way to find out!” You say this as if there is a
way for us to try this and see. Since we cannot measure autophagy,
this statement makes no sense.
Although it will all shake out in the end, or towards it. If
things seem to be “going good” for you as you get older, if
your doctor is always pleasantly surprised at your test results, if
you maintain your vim and vigor as your peers degenerate, maybe it
worked. Maybe it’ll add a few months or years to your life, and
you’ll never quite know because you don’t have an alternate
life in which you didn’t add the turmeric, green tea, and ginger
to your broth for comparison.
At any rate, the mix tastes really, really good. That’s reason
enough to drink the stuff.
What about drinking a cup of black coffee with one tablespoon of
coconut oil blended in? What effect does that have on fasting?
You’ll burn less body fat (because you’re eating 14 grams of
Autophagy will be maintained (because fat has little to no
effect on autophagy).
You may have better adherence. The fast might “feel” easier,
although you might not be “fasting as hard.”
I often have cream in my coffee during a “fast,” and I see
no ill effects. Although as I alluded to in the previous answer,
these things are hard to definitively measure. Much of it is a mix
of speculation, hope, intuition, and faith that our health
practices are helping us and improving our outcomes.
Read my post on
coffee during a fast for more information.
Can you make a Mayo with metformin and increased B12? Thanks
You know what? Let’s try to make this happen.
Start with your favorite mayo recipe. Then, swap out the chicken
egg yolks for two duck egg yolks. Each duck egg contains almost 4
micrograms of B12—more than the daily requirement. For
comparison’s sake, the average chicken egg has about 0.5
At the end, add in a few drops of
barberry extract—barberry is a good natural source of
berberine, an alkaloid whose effects are similar to metformin’s.
I don’t know if the extract will affect the emulsion of the mayo,
but it shouldn’t be too much of a hindrance. Barberry is said to
be bitter, so perhaps add a few pinches of a natural sweetener like
fruit to counteract it.
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
Wack a doos make the world go round. Some of the greatest
thinkers, creators, and doers throughout human history were
considered by many to be insane.
And hey, this is your mother. There’s no shame in helping your
A wack a doo would ask her doc about the potential for crystals
to heal her tumor. A wack a doo would bring a printout of a random
Reddit post to the appointment and use it as proof of her
hypothesis. A wack a doo would ask the staff dietitian for a
Breatharianism protocol. Bringing a legitimate medical article
discussing a specific mutation that has been shown to induce B12
deficiencies in people taking the very same medication your mother
is taking along with genetic results showing she has the mutation
is far from crazy. Do it.
Besides, you’re totally right. A vitamin B12 deficiency (and
the resultant elevated homocysteine levels) is a known risk factor
for blood clots.
That’s it for today, folks. Take care and be sure to leave
your comments and questions down below. Thanks for reading!
Caliendo, Joseph H Vogelman, Jay A. Zimmerman, and Norman
glycine supplementation mimics lifespan extension by dietary
methionine restriction in Fisher 344 ratsThe FASEB
Journal 2011 25:1_supplement, 528.2-528.2
Dear Mark: Broth, Fasting, Coffee, and Metformin (and More)
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