December 18 2018

Dear Mark: Broth, Fasting, Coffee, and Metformin (and More)

By Mark Sisson
8 Comments

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 doctor? No.

Let’s go:

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 cells”.

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 mTOR.

One notable 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 protease activity.

“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.

Touché.

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 it).

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 micrograms.

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 stevia or monk 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 fascinating! ?

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 kin.

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!

References:

Joel BrindVirginia MalloyInes AugieNicholas CaliendoJoseph H VogelmanJay A. Zimmerman, and Norman Orentreich Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 ratsThe FASEB Journal 2011 25:1_supplement528.2-528.2 
TAGS:  dear mark

If you'd like to add an avatar to all of your comments click here!

8 thoughts on “Dear Mark: Broth, Fasting, Coffee, and Metformin (and More)”

Leave a Reply

Your email address will not be published. Required fields are marked *

  1. In ancestral cultures, insanity (dementia praecox) is a prerequisite for shamanic apprentices.

  2. Mark, I’ll be on the lookout for the Primal Kitchen duck egg with barberry extract mayo … coming soon to a store near you. 😉

  3. Was waiting for Mark to come out with that exact recipe for a new mayo. How fortuitous!!

  4. Duck egg mayo sounds delicious!!! Although i raise my own chickens, and their eggs are delicious, I am a sucker for duck eggs! It is VERY interesting to find that they have 8 times the metformin….

    1. I think you’ll find it’s extra B12 in the duck eggs, not metformin 😉

  5. Mark – thanks so much for replying to my post about my Mom, Metformin and MTHFR! The timing is so appropriate as just last night we had a care meeting that I took two of the articles to and brought itup to them. They are going to take a look into it. If only I had your blog post, it could have been a 3rd source of info for them. 🙂

    Thank you again!!

  6. Mark,
    Can you comment/ discuss insulin index/ glycemic index, insulin resistance and LOW blood sugar?

    Here is the thing: my typical blood sugar averages around 50 in the morning [yes I am under medical care] and I have significant insulin resistance due to a higher weight.
    I finally managed to loose about 50 lbs [ok, I went overboard]…but I recently injured myself [knee, again] and can’t work out so I gained weight again.

    Is it diet, exercise, a combination, my body or WHAT? Any thoughts? Any ideas how to manage? IF/ CRF seems to help with stabilizing my sugars and bring my insulin to heel [I do use veg heavy broth during 16/8 fast plan].

    I would be interested in hearing your take. I’ve been reading and think that dairy could be a culprit, even plain greek yogurt…
    Thanx for your writing!!!!!