peptide YY acts to reduce food intake

Leptin can increase oxidative stress, though higher levels in DNAm leptin seem to be "a good thing" (this is entirely consistent)

Ghrelin is the appetite-increasing hormone, and decreasing its levels seems to be "better" than increasing leptin. I wonder if stimulants go after it. Semaglutide mostly lowers ghrelin

https://www.google.com/books/edition/Appetite_and_Food_Intake/JTclDwAAQBAJ?hl=en&gbpv=1&dq=ghrelin+leptin&printsec=frontcover

https://www.google.com/books/edition/The_Hungry_Brain/MVkODQAAQBAJ?hl=en&gbpv=1&dq=leptin+ghrelin&printsec=frontcover

I've had too many nut binges as of late, and eating til I'm full, and this has increased my calorie intake to non-ideal levels (esp b/c I'm impulsive/neurotic and want relief from hunger *now* to focus) - I have zero feedback loops but then this really risks that I suddenly lose my youth before I'm ready for it (this is what I really fear near-term, because I still need all the extra time)....

[anyways i found semaglutide just in time to save me]

Quote

Water consumption may have direct effects on hunger hormones (Clark 2013). These are defined as ghrelin, leptin, insulin, cholecystokinin (CCK) and glucagon‐like peptide‐1 (GPL‐1). The effects are described in Mattes 2010. Ghrelin increases appetite by signalling hunger to the brain and is released primarily in the stomach. Leptin is an appetite suppressant made by fat cells. Insulin is made in the pancreas to enable the body to metabolise sugar (glucose) from carbohydrates and when there is an imbalance this can affect hunger levels. Cholecystokinin stimulates the digestion of fat and protein. GLP‐1 is produced in the gut and released in response to food where it stimulates insulin secretion and inhibits glucagon secretion and this contributes to feelings of satiety (Mattes 2010). Drinking extra water may rate limit the biochemical steps needed to metabolise fat because the glycaemic and insulin index of water is zero. This simplifies the fat breakdown of free fatty acids and the transport of these free fatty acids into the mitochondria where fat is oxidised. Drinking water rather than orange juice was noted to increase fat oxidation in normal weight individuals following a breakfast when tested on two consecutive days, even when they consumed more calories than they expended and engaged in no other intervention to reduce the calorie balance (Stookey 2012). Two days is not enough time to conclude that extra water intake is effective as a weight loss tool, however it is a promising observation.

Quote

Semaglutide improved leptin sensitivity and anorexigenic signaling but lessened orexigenic signaling

https://journals.physiology.org/doi/full/10.1152/ajpgi.2001.281.3.G752 -  acarbose might increase incretins on carb-containing meals too...

I'm wondering if the diaas concept can be used advantageously even  in those who practice CR. My first thought is: optimizing amino acid availability allows to decrease calories with minimum risk of malnutrition due to lack of adequate EAAs.

The DIAAS concept, from the wiki voice and a free review article.

Quote

 

Digestible Indispensable Amino Acid Score (DIAAS) is a protein quality method proposed in March 2013 by the Food and Agriculture Organization to replace the current protein ranking standard, the Protein Digestibility Corrected Amino Acid Score (PDCAAS).

The DIAAS accounts for amino acid digestibility at the end of the small intestine, providing a more accurate measure of the amounts of amino acids absorbed by the body and the protein’s contribution to human amino acid and nitrogen requirements. This is in contrast to the PDCAAS, which is based on an estimate of digestibility over the total digestive tract. Values stated using this method generally overestimate the amount of amino acids absorbed.^[1]

 

Eric Verdin mentioned this.

https://blog.trudiagnostic.com/epigenetic-patterns/

https://www.medrxiv.org/content/10.1101/2021.09.21.21263912v1.full (CR non-significantly increases DNAm age on Horvath/Hannum clocks). They do help with DunedinPACE and GrimAge. These, again, are just for PBMCs (which may or may not be representative of cells elsewhere - CR is known to depress white blood cell count). But decreases in WBC count, I presume, would at least indicate that CR'd HSCs divide less, which would presumably better maintain their telomere lengths.

Now, my question: I hear and read much about people getting their omega-3 needs met by flax seeds or flax seed oil, or, for some of us, fish, others, supplements, but I don't hear much about chia seeds. Is there some problem with them I haven't seen?

I created an Excel spreadsheet with 250 calorie amounts of nuts, a few seeds, and a few other fatty items in order to help guide my fatty food choice, and was amazed at how nutritious chia seeds are!

They're bland-tasting, to be sure -- is that why people don't get excited about them? Otherwise, lots of minerals, but no scary amounts of Cu or Mn (though not really low Mn), far more vitamins than most nuts or seeds, even a lot of carotenoids. Fairly low SFA, to boot. And then all that ALA.

Is there some hidden danger?

Zeta

reddit deleted the /r/semaglutidecompounds subreddit a few days ago... sad, especially b/c there are so many psychedelic subreddits (eg DrugNerds) that go untouched...

I've read and reviewed The CR Way, have been counting and restricting my calories while meeting the DRI of protein and carbs, and am awaiting the delivery of several books recommended on the Calorie Restriction website (here: https://www.crsociety.org/resources/cr_guide ). My question now is how much salt should I be aiming for on a daily basis? Do you guys shoot for 100% of the US RDA (it might be a DRI I haven't much looked into it) or do you shoot for less than that? In The CR Way the McGlothins note that many CR practitioners likely keep their blood pressure low by reducing their salt intake but I wasn't sure if that meant less than the RDA/RDI/DRI or equal to the RDA/RDI/DRI.

Thanks for the info guys!

Max

I practiced CR for approximately 2 years.  I am mid 50's, 6'2 height, and currently weigh 155lbs, moderately active (3 - 4 x week) both cardio and calisthenics.  I am also vegan for 9+ years. Initially, upon starting CRON, I went from 168 lbs to about 138 lbs eating 1900 Kcal/day (food measured w/scale, eating 633kCal x 3 meals/day). I used cronometer to ensure I was meeting nutrient numbers to avoid undernutrition. The first year was easy and where I lost the majority of weight, no adverse issues. Entering into the second quarter of the second year, I started having strange psychological food cravings and feeling the need to binge eat at odd times of the day, i.e., one example, probably a 3,000kCal meal of dates and pretzels (weird food combinations, I know).  I attempted different techniques to combat the sensations of my brain telling me to eat something ridiculous hand over fist and failed, i.e., eating a small meal of cruciferous veggies to feel 'full' about an hour prior to the last meal of the day.  I tried to maintain CR over the next two quarters of the second year and gradually couldn't maintain it.   I abandoned CR at the end of the second year but maintained veganism easily, but probably started freely eating ~2500 to 2900 kCal per day (estimate) and have gained about 15 lbs of bodyweight, but am still 'fit' and lean.  I finally felt 'happy', obviously eating to satiation with no amount or calorie constraints. I have researched CRON fairly extensively, and understand the (potential) benefits and would like to try to re-engage with it in earnest, but this time succeed.  Any suggestions?  Best regards to you, Ash.

It was the time when my fasting glucose often hit 105 mg/dL, and I used to complain on this board and started a low carb regime.

After these 2+ years of more moderate exercise, not regular sleep, moderate and continuos daily activity, low carb turned into higher carbs the latest months, I lost 10 kg, presently hitting a minimum of 63 kg in bodyweight, BMI 22. In the meanwhile I also stopped taking creatine. Fasting glucose now is usually 95 mg/dL.

The main factor of the weightloss was most probably what I call spontaneous CR, that is I went naturally into a lower caloric regime, which has been in the region of 1800 kCals daily. Spontaneous because that what my body required apparently, I suffered no hunger but if I tried to eat more, I would feel stuffed and uneasy. A natural neurological way the body wanted to trigger catabolism and take the bodyweight down, for reasons unknown to me. I also ceased to track food with cronometer, because that's a measurement which influences the outcome, no doubt about it, at least in my case.

Muscle mass of course suffered, even at a protein intake of 136% the RDA.

Considerations on protein and lean mass: perhaps those advocating high protein to spare muscle mass in not young individuals are right. I kept exercising although more moderately, but the Mechanic signal was not enough, at least with an evidently insufficient energy intake. I'm also convinced that even by eating 200% protein RDA, a lesser energy intake would have caused weightloss regardless.

Present strategy: I'm going to try and recoup the lean bodyweight, hitting a target of 70 kg, or at least 67.5 without creatine. It won't be easy, it will involve eating proteins before vegetables and daily tracking food and weight. It would be far easier with unlimited amount of sugars, the glucose signal is sometimes more powerful than the leucine signal in activating mTOR and increasing muscle mass, as I've noticed myself in the past, probably because glucose and insulin/IGF-1 go hand in hand.

Signature Select colossal ripe pitted olives has 1 calorie/gram (lower than other brands!). I don't know if this calorie label can be completely trusted though.

https://www.amazon.com/365-Everyday-Value-Organic-Kalamata/dp/B074H7L7F1/ref=sr_1_6_f3_0o_fs?crid=XZA0PCMFR8PC&keywords=olives&qid=1673352714&sprefix=olive%2Caps%2C115&sr=8-6 has 3 calories per gram of olive.

I have premium EVOO for the polyphenols, so for real olives I just want low calorie density

https://sureketo.com/best-for-keto/olives

(though lower calorie density means higher carbs, which may not be great for keto)

Brian

[1]

New Review:

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(The review is behind a pay wall, and cutting and pasting isn't possible.)

Many labs are affected by CR or other healthy diets. Eg WBC is lower under WFPB vegan & CR diets. BUN levels are lower in low-protein diets. Etc.

I'm aware that Luigi Fontana has published some studies with some lab values (eg https://www.pnas.org/doi/10.1073/pnas.0308291101) but I haven't seen any papers that cover even the full range of stuff a super-common & inexpensive CBC would provide. Eg BUN is not in that paper. The CALERIE cohort has been studied extensively with several papers published---do any datasets publicly available anywhere present the summary stats for most CBC blood labs for this cohort? I know Fontana did some work with members of the CR Society a ways back---is there a summary table with labs for those tests that covers more than the basic half dozen CVD risk factors? I don't have time to trace down all the papers and study what's provided in the supplemental material at the moment, and curious if someone else has done that or if they know of a place where researchers have put the summary stats data for the broader list of markers.

I know Dean has shared his labs in these forums. Have there been any efforts to collect more than n=1 here, even if only n=5ish or something like that?

I'm just wondering what's best in terms of a CR diet.

Is it better to eat one meal a day ( or 2 meals) and fast the rest of the day or eating smaller amounts of food, maybe like 3 or 4 times a day.

It seems to me that CR proponent are divided into these two camps: Intermittent fasting Vs a Luigi Cornaro type diet.

There are those who advocate cramming all your calories within an eating window and those that say don't eat until full, or never eat if not hungry regardless of time of day.

Any thoughts?

The important difference between consumption of dietary cholesterol, which has a negligible influence on heart disease risk, and cholesterol produced endogenously in the body (which can be a marker of risk, depending on a complete profile)....

So why exactly is it that eggs are so damn bad?

http://www.whfoods.com/genpage.php?tname=foodspice&dbid=92

https://www.amazon.ca/Bicarbonate-Food-Grade-Crystalline-Elos-Premium/dp/B09ZTPGBX8/ref=sr_1_6?crid=3OBYKM8AXYZ76&dib=eyJ2IjoiMSJ9.mNqQFo_CrZAF7JCvauupNNLeK0VZYpW8RBga5x34aNyzbYAHqxBaj5ChePjxsHOWUL-026X4F_NltXuDOqBrjO7qvYQ_OH9n9V0wJAk2oVBmdH92GLrwSxBhjE9TR9B4FS9bNDg14FdVIfhzMWP3jvIy4vbAG8N28GDbvC5KBlwM5lLHHGohVAxQNQGAlDJoQbADgeIXwYjznq7Lo0jDXljKzNyrxlRuL0SKyR-sunBjKKawNvGR-9DRegJIvockeNx8g4GqnAOyyKKbg7pJvCMm3nNsMLsEakGJnw6qW_8.AKHwvpA333rJooKBBS2qNHjFKv34DS5LxvW8Rx-0gzc&dib_tag=se&keywords=potassium+powder&qid=1711324337&sprefix=potassium+powder%2Caps%2C107&sr=8-6

But it would be my 7th regular  powder to take lol!  Or I could use it in my cooking if K doesn't get destroyed by the heat...

My name is Fred. I've posted on here quite a few times in the past (years ago) and am thinking about trying to wean myself onto a CR diet yet again. I remember the fun challenge of trying to get the most nutrients in the fewest calories the first time I attempted to start the diet.

My question is this -- What kinds of foods would you recommend I eat to get the most nutrition while on the diet? I know that green leafy vegetables are the best choice, so I am basing my diet on salads (mostly cabbage, romaine and spinach). What should I add to the salad to get the most nutrition? I have tried Cronometer but I get frustrated easily and know it's easier to simply ask the question on here and get quick answers from long-time practitioners. What are the basic foods I should add to the salad to get the best results??

I would appreciate any and all feedback.

I used to cook for my family when we were 4 rather than 3 . But now that it is just the three of us, and my daughter has an extremely busy schedule, my wife and daughter's eating schedule is pretty irregular. So they cook for themselves.

• [Get up at 2:45am - yes I'm kind of a early riser  ]
• 4min - straight arm planking
• 2min - 100 body weight squats
• 10min - "10 minute abs" workout - Originally from YouTube video of that name, but after doing it several thousand times, I've got it memorized. . Video embedded at bottom. Warning - this will really hurt anyone not used to doing an ab workout, but her accent is strangely compelling...
• 20min - Jogging on treadmill at 4mph and 15% incline (very steep). 1.07miles, 200 kcal
• 120min - Stationary road bike. Modest intensity. HR around 95bpm. My Resting HR is about 45bpm.
• [breakfast - 1.5 hours]
• 10min - One mile run outdoors. Moderate pace . usually with my dog.
• 20min - Resistance training. 4day split to work all body parts on successive days, but giving each enough time to recover. Little rest between sets to keep it mildly aerobic. Pretty light weights. Pull-ups, pushups, light squats, triceps extensions, curls, shrugs, etc. All the standard exercises. Using dumbbells and body weight.
• 4min straight arm planking
• 2min - 100 body weight squats
• 2min - Ab Slide machine. Quite a good Ab exerciser
• 90min - Stationary road bike again.
• [Time now around 10:30am - Shower & 6min inversion therapy (to decompress spine and stretch back) & 20min power nap]
• [Puttering around for a while, light food prep, errands etc - 1-2 hours]
• 10min - One mile run outdoors. With dog.
• ~240min - pedalling at my bike desk while reading, surfing web, posting to CR forums
• [Off and on throughout afternoon evening - spend time with wife and daughter, especially when they eat dinner]
• 30min - brisk walk with my wife (and dog)
• [8:00pm - bedtime. 8:15 sound asleep]

So in total I run for about 40min, do resistance training / calisthenics for about 45min, walk 30-45min, and then pedal for about 7h per day. On an average day, my Fitbit tells me I log about 45K steps (or step equivalents, including bike pedal revolutions), and about 23 miles. All of it at home, by myself (except if you count the mile walk with my wife and jogging with my dog    ). I don't enjoy the hassle of working out with others at a gym. I don't seem to need the motivation of having other people around to exercise with.

• I like to eat, and to stay slim. Extreme exercise let's me do both.
• I'm exploring the possibility of getting CR benefits while eating lots of calories, but burning them off via lots of exercise and cold exposure.
• It makes me feel good. I like the endorphins, opiates, whatever makes exercise feel good.
• With my stationary bike and bike desk, I'm able to do other things while pedaling, like composing this message!
• I like being different from other people.
• I like pushing myself to extremes, to see what's possible. Pushing the envelope of human possibliity.
• I think exercising one's abilities and strengths is why we are here, and what makes life meaningful and significant. My biggest strength is probably self-discipline / conscientiousness.
• Exercising discipline strengthens the will.  As Nietzsche said in Twilight of the Idols, "From life's school of war, what does not kill me makes me stronger." He was a big proponent of hormesis before it became fashionable. 
• I hope being very different from others, and sharing my results, will enable people (like you!) to learn from my experiences and experiments, and figure out what might work best for them. 

Regarding sleep. I sleep for 6.5 hours per day (8:15pm - 2:45am) + a 20min power nap. Lately I've been sleeping like a baby, without my former problem of early waking (unless you count 2:45am as early  ).

It is the richest food source of vitamin K2 (menaquinone-7 or MK-7) with 1 mg (1000 mcg) of K2 per 100g natto. That is about 20x higher than the next highest source, certain cheeses like Gouda. Unlike vitamin K1 which is found primarily in leafy greens, there is virtually no vitamin K2 in regular fruits and vegetables.

Why should we care about vitamin K2 you ask?

First and foremost because it has been shown to be protective against osteoporosis [1-2], a concern for CR practitioners. From [2], a study of 244 postmenopausal women supplemented with 180mcg/day of Vitamin K2 (MK-7) for three years: 

Another significant benefit of Vitamin K2 is for cardiovascular health. Vitamin K2 seems to prevent artery calcification (aka hardening of the arteries) [3-5], which happens when calcium circulating in the blood is turned into a crust in the arteries. In study [5] the same group of researchers from [2] measured arterial calcification in the same 244 postmenopausal women on 180mcg/day of K2 for three years, and found multiple markers of arterial stiffness improved with K2 supplementation, concluding:

But those were studies of direct supplementation of vitamin K2 (MK-7), rather than getting it from food. Does eating natto actually raise serum MK-7 levels? Thankfully the answer is yes, according to [6]:

So where to get natto?

I buy my natto in frozen form at my local asian market, for about $2.50 for four styrofoam containers each of which contains about 50g of natto. Here is what the package of four look like:

I eat half of a container's worth of natto per day (cost ~ $0.30/day). That 25g of natto per day provides about 250mcg of Vitamin K2 (MK-7), which is about 30% more than the dose shown to improve bone health [2] and reduce arterial stiffness [5] in postmenopausal women.

What's natto like you ask?

There is no getting around the fact that it looks pretty gross, and has a very slimy texture. As a result, many people can't stomach it, but I actually enjoy the taste, especially when mixed into the serving of other legumes and starches I eat. Below is a photo of natto in the styrofoam container. Pretty appetizing, huh?! The chopsticks in the photo are helpful for scale:

For those of you who would be too grossed out by natto to eat it, there are supplements available. In fact I take one of these* to increase my K2 beyond what I get from natto - adding an extra 100mcg MK-7 per day for $0.09. But I'm always in favor of getting nutrients from food sources when practical. This is one of the rare cases where the natural food source is price competitive with supplement sources. So for me natto is a good choice.

Does anyone else eat natto? If not, you might consider giving it a try!

[Note: This post does not address Natto's brain health benefits. For discussion of that, see this post further down this thread.]

--Dean

*Note - I've updated my supplement regime to this vegan NOW Foods brand K2 supplement, to make sure I'm getting K2 in MK-7 form, rather than (mostly) MK-4 per my previous supplement.

---------

[1] J Bone Miner Metab. 2014 Mar;32(2):142-50. doi: 10.1007/s00774-013-0472-7. Epub

2013 May 24.

Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism
and prevents forearm bone loss in postmenopausal Japanese women.

Koitaya N(1), Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y,
Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishimi Y.

Author information:
(1)Department of Food Function and Labeling, National Institute of Health and
Nutrition, 1-23-1 Toyama, Shinjyuku-ku, Tokyo, Japan.

Menaquinone-4 (MK-4) administered at a pharmacological dosage of 45 mg/day has
been used for the treatment of osteoporosis in Japan. However, it is not known
whether a lower dose of MK-4 supplementation is beneficial for bone health in
healthy postmenopausal women. The aim of this study was to examine the long-term
effects of 1.5-mg daily supplementation of MK-4 on the various markers of bone
turnover and bone mineral density (BMD). The study was performed as a randomized,
double-blind, placebo-controlled trial. The participants (aged 50-65 years) were
randomly assigned to one of two groups according to the MK-4 dose received: the
placebo-control group (n = 24) and the 1.5-mg MK-4 group (n = 24). The baseline
concentrations of undercarboxylated osteocalcin (ucOC) were high in both groups
(>5.1 ng/ml). After 6 and 12 months, the serum ucOC concentrations were
significantly lower in the MK-4 group than in the control group. In the control
group, there was no significant change in serum pentosidine concentrations.
However, in the MK-4 group, the concentration of pentosidine at 6 and 12 months
was significantly lower than that at baseline. The forearm BMD was significantly
lower after 12 months than at 6 months in the control group. However, there was
no significant decrease in BMD in the MK-4 group during the study period. These
results suggest that low-dose MK-4 supplementation for 6-12 months improved bone
quality in the postmenopausal Japanese women by decreasing the serum ucOC and
pentosidine concentrations, without any substantial adverse effects.

PMID: 23702931

------------

[2] Osteoporos Int. 2013 Sep;24(9):2499-507. doi: 10.1007/s00198-013-2325-6. Epub

2013 Mar 23.

Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in
healthy postmenopausal women.

Knapen MH(1), Drummen NE, Smit E, Vermeer C, Theuwissen E.

Author information:
(1)VitaK, Maastricht University, Oxfordlaan 70, 6229 EV, Maastricht, The
Netherlands.

We have investigated whether low-dose vitamin K2 supplements (menaquinone-7,
MK-7) could beneficially affect bone health. Next to an improved vitamin K
status, MK-7 supplementation significantly decreased the age-related decline in
bone mineral density and bone strength. Low-dose MK-7 supplements may therefore
help postmenopausal women prevent bone loss.INTRODUCTION: Despite contradictory
data on vitamin K supplementation and bone health, the European Food Safety
Authorities (EFSA) accepted the health claim on vitamin K's role in maintenance
of normal bone. In line with EFSA's opinion, we showed that 3-year high-dose
vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation
improved bone health after menopause. Because of the longer half-life and greater
potency of the long-chain MK-7, we have extended these investigations by
measuring the effect of low-dose MK-7 supplementation on bone health.
METHODS: Healthy postmenopausal women (n = 244) received for 3 years placebo or
MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip,
and femoral neck was measured by DXA; bone strength indices of the femoral neck
were calculated. Vertebral fracture assessment was performed by DXA and used as
measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC)
and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of
vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years
of treatment.
RESULTS: MK-7 intake significantly improved vitamin K status and decreased the
age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not
at the total hip. Bone strength was also favorably affected by MK-7. MK-7
significantly decreased the loss in vertebral height of the lower thoracic region
at the mid-site of the vertebrae.
CONCLUSIONS: MK-7 supplements may help postmenopausal women to prevent bone loss.
Whether these results can be extrapolated to other populations, e.g., children
and men, needs further investigation.

PMID: 23525894

-----------

[3] Acta Physiol Hung. 2010 Sep;97(3):256-66. doi: 10.1556/APhysiol.97.2010.3.2.

Vitamin K and vascular calcifications.

Fodor D(1), Albu A, Poantă L, Porojan M.

Author information:
(1)University of Medicine and Pharmacy, 2nd Internal Medicine, Clinic Iuliu
Hatieganu, Cluj-Napoca, Romania. dfodor@umfcluj.ro

The role of vitamin K in the synthesis of some coagulation factors is well known.
The implication of vitamin K in vascular health was demonstrated in many surveys
and studies conducted over the past years on the vitamin K-dependent proteins
non-involved in coagulation processes. The vitamin K-dependent matrix Gla protein
is a potent inhibitor of the arterial calcification, and may become a
non-invasive biochemical marker for vascular calcification. Vitamin K(2) is
considered to be more important for vascular system, if compared to vitamin K(1).
This paper is reviewing the data from recent literature on the involvement of
vitamin K and vitamin K-dependent proteins in cardiovascular health.

PMID: 20843764

----------------

[4] Nutrients. 2015 Aug 18;7(8):6991-7011. doi: 10.3390/nu7085318.

High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a
Murine Model of Extraosseous Calcification.

Scheiber D(1), Veulemans V(2), Horn P(3), Chatrou ML(4), Potthoff SA(5), Kelm
M(6,)(7), Schurgers LJ(8), Westenfeld R(9).

Author information:
(1)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty,
University Duesseldorf, Duesseldorf 40225, Germany.
daniel.scheiber@med.uni-duesseldorf.de. (2)Division of Cardiology, Pulmonology,
and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf
40225, Germany. verena.veulemanns@med.uni-duesseldorf.de. (3)Division of
Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University
Duesseldorf, Duesseldorf 40225, Germany. patrick.horn@med.uni-duesseldorf.de.
(4)Department of Biochemistry, Cardiovascular Research Institute Maastricht,
Maastricht University, Maastricht 6229 ER, The Netherlands.
m.chatrou@maastrichtuniversity.nl. (5)Department of Nephrology, University
Duesseldorf, Medical Faculty, Duesseldorf 40225, Germany.
sebastian.potthoff@med.uni-duesseldorf.de. (6)Division of Cardiology,
Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf,
Duesseldorf 40225, Germany. malte.kelm@med.uni-duesseldorf.de. (7)Cardiovascular
Research Institute Duesseldorf, University Duesseldorf, Medical Faculty,
Duesseldorf 40225, Germany. malte.kelm@med.uni-duesseldorf.de. (8)Department of
Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht
University, Maastricht 6229 ER, The Netherlands.
l.schurgers@maastrichtuniversity.nl. (9)Division of Cardiology, Pulmonology, and
Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225,
Germany. ralf.westenfeld@med.uni-duesseldorf.de.

Cardiovascular calcification is prevalent in the aging population and in patients
with chronic kidney disease (CKD) and diabetes mellitus, giving rise to
substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP)
is an important inhibitor of calcification. The aim of this study was to evaluate
the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on
the development of extraosseous calcification in a murine model. Calcification
was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham
operated animals served as controls. Animals received high or low MK-7 diets for
12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance,
and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and
myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline
phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited
cardiovascular calcification and decreased aortic alkaline phosphatase tissue
concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger
ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial
hypertension with secondary myocardial hypertrophy and increased elastic fiber
breaking points in the arterial tunica media did not change with MK-7
supplementation. Our results show that high-dose MK-7 supplementation inhibits
the development of cardiovascular calcification. The protective effect of MK-7
may be related to the inhibition of secondary mineralization of damaged vascular
structures.

PMCID: PMC4555157
PMID: 26295257

-------------

[5] Thromb Haemost. 2015 May;113(5):1135-44. doi: 10.1160/TH14-08-0675. Epub 2015 Feb

19.

Menaquinone-7 supplementation improves arterial stiffness in healthy
postmenopausal women. A double-blind randomised clinical trial.

Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C(1).

Author information:
(1)Cees Vermeer, PhD, VitaK, Maastricht University, Biopartner Center Maastricht,
Oxfordlaan 70, 6229 EV Maastricht, The Netherlands, Tel: +31 43 388 5865, Fax:
+31 43 388 5889, E-mail: c.vermeer@vitak.com.

Observational data suggest a link between menaquinone (MK, vitamin K2) intake and
cardiovascular (CV) health. However, MK intervention trials with vascular
endpoints are lacking. We investigated long-term effects of MK-7 (180 µg
MenaQ7/day) supplementation on arterial stiffness in a double-blind,
placebo-controlled trial. Healthy postmenopausal women (n=244) received either
placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid
stiffness (intima-media thickness IMT, Diameter end-diastole and Distension) were
measured by echotracking. Regional aortic stiffness (carotid-femoral and
carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured
using mechanotransducers. Circulating desphospho-uncarboxylated matrix
Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6),
high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and
markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM),
E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline
dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of
acute phase markers (APMscore) and of markers for endothelial dysfunction
(EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index
βsignificantly decreased in the total group, whereas distension, compliance,
distensibility, Young's Modulus, and the local carotid PWV (cPWV) improved in
women having a baseline Stiffness Index β above the median of 10.8. MK-7
decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers
for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7
supplements improves arterial stiffness in healthy postmenopausal women,
especially in women having a high arterial stiffness.

PMID: 25694037

----------

[6] J Bone Miner Metab. 2000;18(4):216-22.

Intake of fermented soybean (natto) increases circulating vitamin K2
(menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal
individuals.

Tsukamoto Y(1), Ichise H, Kakuda H, Yamaguchi M.

Author information:
(1)Central Research Institute, Mitsukan Group Co., Ltd., Aichi, Japan.

Changes in circulating vitamin K2 (menaquinone-7, MK-7) and gamma-carboxylated
osteocalcin concentrations in normal individuals with the intake of fermented
soybeans (natto) were investigated. Eight male volunteers were given sequentially
fermented soybeans (natto) containing three different contents of MK-7 at an
interval of 7 days as follows: regular natto including 775 micrograms/100 g (MK-7
x 1) or reinforced natto containing 1298 micrograms/100 g (MK-7 x 1.5) or 1765
micrograms/100 g (MK-7 x 2). Subsequently, it was found that serum MK-7 and
gamma-carboxylated osteocalcin concentrations were significantly elevated
following the start of dietary intake of MK-7 (1298 or 1765 micrograms/100 g).
Serum undercarboxylated osteocalcin concentrations were significantly decreased
by dietary MK-7 (1765 micrograms/100 g) supplementation. Moreover, the changes in
serum MK-7 level with the frequency of dietary natto intake were examined in 134
healthy adults (85 men and 39 women) without and with occasional (a few times per
month), and frequent (a few times per week) dietary intake of regular natto
including MK-7 (775 micrograms/100 g). Serum MK-7 and gamma-carboxylated
osteocalcin concentrations in men with the occasional or frequent dietary intake
of natto were significantly higher than those without any intake. The present
study suggests that intake of fermented soybean (natto) increases serum levels of
MK-7 and gamma-carboxylated osteocalcin in normal individuals.

PMID: 10874601

As you can see, I've got hoops (made from PVC pipes) and nets over the raised beds to protect the plants from deer, which are ubiquitous here in Western Pennsylvania. FYI, the beds are both 8' long by 4' across.

This list of plants in these two beds include:

• Kale (curly & dino)
• Mustard Greens
• Broccoli
• Arugula
• Leaf Lettuce (green and red)
• Endive
• Red Swiss Chard
• Nasturtium
• Red-veined Sorrel
• Basil (sweet, cinnamon, lemon)
• Sage
• Curly Parsley
• Lemon Balm
• Oregano
• Lemon Thyme
• Rosemary
• Stevia
• Alpine Strawberries
• Eggplant

Not shown in these photos:

• Tomatoes (cherry, black russian, yellow pear)
• Tomatillos
• Lemon Cucumbers
• Onions (red & yellow)
• Garlic
• Acorn Squash - spontaneously growing in my compost pile!
• Cantaloupe -  spontaneously growing in my compost pile!

Most of these were grown from seeds, so cost me almost nothing. Between harvesting & watering, I spend about 30min every other day tending my garden.

Coupled with the 3oz/day of sprouts and microgreens I grow indoors year-round, the harvest from these two beds provides about a pound (450g) of fresh organic leafy greens per day from late-June through October, saving hundreds of dollars over the season. Plus all the savings from the 'solid' vegetables/fruits listed at the bottom.

The plants I've listed are the one's I've found through trial and error to grown the best and produce the most in this part of the country. All of them (except for squash, cantaloupe, onions, garlic & eggplant) can be harvested a few leaves / fruits at a time over the entire season, so I don't get overwhelmed by more than I can eat of any one item, and I can harvest a little bit from each of them every other day to maximize freshness and variety.

Does anyone else have a garden or gardening tips they care to share, or any questions about my gardening practice?

--Dean

I'm curious if sustaining oneself on a diet solely consisting of raw fruits, nuts, and vegetables is feasible. Are there potential risks of malnutrition or other long-term effects on the body associated with this diet? My mother is deeply committed to this eating pattern, believing it to be the optimal choice for health and longevity, asserting that it can even cure various diseases. I'm interested in hearing your perspective on this matter.

By now I've tried Longo's FMD, based upon data drawn from the patent application material and his book, data which I posted in another thread. Basically, as I construe it the daily diet is made up of about 3 pounds of vegetables, either raw and cooked, with few nuts (about 20 grams on the average), limited amount of EVOO, possibly avocado. 

I must say that, as far as the practical details go, the diet was a success. I felt the same symptoms of a water-only fast but far milder. Today, on my 5th day, I was pretty energetic whereas in my 5th day of water-only I was totally whacked and mentally unable to focus. I lost about one pound of bodyweight per day, whereas on water-only I lost twice as much. My blood glucose reading on the morning of the 5th day was 81 mg/dl, a little less than my last reading durign a usual day, 86 mg/dl. I'm going to post the cornometer details, On the 1st day I ate 300 Kcal less than the allowed quota, simply because I wasn't hungry. On the last day I ate 100 kCal less, whereas on other days I ate about 750 kCal a day, the allowed quota for my bodyweight range.

I'm going to post the cronometer results of the single days, maybe you guys are going to give some useful tips for the next FMD, which I'll make sure to reply at the suggested frequency.

As discussed in this thread, research suggests that the gut microbiome can have a dramatic impact on physical, and even mental, health. But the relationship between the gut and health remains pretty murky, and research in the area is still in its infancy.

Today everyone's favorite nutrition pundit, Dr. Greger   had what I think even his skeptics will agree was a helpful video outlining one mechanistic account of how gut bacteria impact health via their influence on systemic inflammation, which itself has been implicated in most of the diseases of aging.

In the video, he suggests that our body has a 'love/hate' relationship with the bacteria in our gut. On the one hand, some bacteria are quite helpful, turning what would otherwise be indigestible food (i.e. fiber) into useful metabolites, like short chain fatty acids that our body can burn as fuel. On the other hand, some bacteria like cholera or e. Coli are quite detrimental to our health, and can sometimes be fatal.

So how does our immune system, which is tasked with coping with all these bacteria, handle the job? Specifically, how does it distinguish between the good bacteria which it should ignore and the bad bacteria which it should combat by triggering an inflammatory response?

Dr. Greger points to research [see his citations at the bottom of this post] suggesting that the immune system uses the presence of a high level of the short chain fatty acid butyrate as the signal to distinguish between a gut populated with mostly 'good' vs. mostly 'bad' bacteria. More specifically, during our evolutionary heritage, when our ancestors were all eating a very high fiber (> 100g) diet, a healthy gut population would have generated a lot of butyrate, signally 'all clear' to the immune system, which would 'stand down' as a result. But when the gut became overgrown with 'bad' bacteria (which don't produce butyrate), the immune system would notice this lack of butyrate and swing into action, triggering a (systemic) inflammatory response to combat the bad bacteria. 

The problem is that today, people are eating a crappy, low-fiber, toxin-loaded Western diet, and as a result, even if a person has mostly 'good' bacteria in their gut, the bacteria don't have enough of their food (i.e. fiber) to produce much butyrate. The immune system interprets this lack of butyrate as a sign that the gut is infested with bad bacteria, and so triggers a persistent, systemic inflammatory response in order to fight the (non-existent) threat from the (non-existent) bad bacteria. This permanent inflammatory state in turn leads to all kinds of chronic disease outcomes, from cardiovascular disease, to inflammatory bowel disease, to neurodegenerative diseases like Alzheimer's.

That's where Dr. Greger leaves the story, at least in this video.

So which types of bacteria (as reported by uBiome) are the 'good', butyrate-producing guys that will signal our immune system that 'all is well'? 

According to [1]:

Eighty percent of the butyrate-producing isolates [from a sample of human gut bacteria] fell within the XIVa cluster of gram-positive bacteria

The common gram-positive bacteria reported at the highest level of the uBiome reports is the phylum "firmicutes". From the firmicutes wikipedia entry:

The Firmicutes (Latin: firmus, strong, and cutis, skin, referring to the cell wall) are a phylum of bacteria, most of which have Gram-positive cell wall structure.

In contrast, the other common high-level phylum of bacteria reported by uBiome are the gram-negative, non-butyrate-producing Bacteroides. From the microbiome wiki entry for Bacteriodes:

Bacteroides are gram-negative, non-spore-forming, anaerobic, and rod-shaped bacteria. 

So overall, to first approximation, it appears preferable to have an abundance of firmicutes and a relative dearth of bacteroides on one's ubiome report of gut bacteria, at least from the perspective of avoiding the ill effects of systemic inflammation by maintaining a high level of butyrate. But it is undoubtedly not quite this simple. In fact I started down a rabbit hole of reading about gut bacteria that I can't entirely make heads or tails of, and that reinforced my belief that researchers a long way from understanding the impact of gut bacteria on human health - see Note 1 below for one such complication.

If anyone has a different, better understanding of all of this, and wants to challenge Dr. Greger's account as an oversimplification, I'd love to hear about it!  

--Dean

---------

Note 1: Perhaps paradoxically, vegetarians have been found to have relatively more non-butyrate producing bacteroides in their guts than omnivores, and the resulting relative dearth of energy-harvesting, butyrate-producing firmicutes in vegetarians has been used to explain the leanness of vegetarians compared to omnivores [2]. In other words, the obesogenic gut microbiome profile appears to be a higher ratio of firmicutes to bacteroides, since firmicutes are able to extract more calories from food by turning fiber into the short chain fatty acid butyrate which the body can metabolize for energy. So while firmicutes may be helpful for signalling the immune system that 'all is well' via butyrate production, the resulting abundance of butyrate produced by the firmicutes may increase one's tendency to gain weight by extracting more calories from food. But if this is true, why do firmicute-lacking vegetarians have lower levels of inflammation, and generally better health, than omnivores? Perhaps your average vegetarian doesn't actually eat that much fiber, so they aren't feeding their firmicutes sufficiently... As I said, it is complicated...

-----------

[1] Appl Environ Microbiol. 2000 Apr;66(4):1654-61.

Phylogenetic relationships of butyrate-producing bacteria from the human gut.

Barcenilla A(1), Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, Flint
HJ.

Author information:
(1)Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, United Kingdom.

Butyrate is a preferred energy source for colonic epithelial cells and is thought
to play an important role in maintaining colonic health in humans. In order to
investigate the diversity and stability of butyrate-producing organisms of the
colonic flora, anaerobic butyrate-producing bacteria were isolated from freshly
voided human fecal samples from three healthy individuals: an infant, an adult
omnivore, and an adult vegetarian. A second isolation was performed on the same
three individuals 1 year later. Of a total of 313 bacterial isolates, 74 produced
more than 2 mM butyrate in vitro. Butyrate-producing isolates were grouped by 16S
ribosomal DNA (rDNA) PCR-restriction fragment length polymorphism analysis. The
results indicate very little overlap between the predominant ribotypes of the
three subjects; furthermore, the flora of each individual changed significantly
between the two isolations. Complete sequences of 16S rDNAs were determined for
24 representative strains and subjected to phylogenetic analysis. Eighty percent
of the butyrate-producing isolates fell within the XIVa cluster of gram-positive
bacteria as defined by M. D. Collins et al. (Int. J. Syst. Bacteriol. 44:812-826,
1994) and A. Willems et al. (Int. J. Syst. Bacteriol. 46:195-199, 1996), with the
most abundant group (10 of 24 or 42%) clustering with Eubacterium rectale,
Eubacterium ramulus, and Roseburia cecicola. Fifty percent of the
butyrate-producing isolates were net acetate consumers during growth, suggesting
that they employ the butyryl coenzyme A-acetyl coenzyme A transferase pathway for
butyrate production. In contrast, only 1% of the 239 non-butyrate-producing
isolates consumed acetate.

PMID: 10742256

------------

[2] Ann Nutr Metab. 2009;54(4):253-7. doi: 10.1159/000229505. Epub 2009 Jul 27.

Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians
using qPCR and PCR-DGGE fingerprinting.

Liszt K(1), Zwielehner J, Handschur M, Hippe B, Thaler R, Haslberger AG.

Author information:
(1)Department of Nutritional Sciences, University of Vienna, Vienna, Austria.

BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative
changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in
faecal microbiota associated with a vegetarian diet.
METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians
and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE
fingerprinting, principal component analysis (PCA) and Shannon diversity index.
RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores,
a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%)
and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which
were not significant due to high interindividual variations. PCA suggested a
grouping of bacteria and members of Clostridium cluster IV. Two bands appeared
significantly more frequently in omnivores than in vegetarians (p < 0.005 and p <
0.022). One was identified as Faecalibacterium sp. and the other was 97.9%
similar to the uncultured gut bacteriumDQ793301.
CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by
decreasing the amount and changing the diversity of Clostridium cluster IV. It
remains to be determined how these shifts might affect the host metabolism and
disease risks.

Copyright 2009 S. Karger AG, Basel.

PMID: 19641302

Dr Greger Video References:

C J North, C S Venter, J C Jerling. The effects of dietary fibre on C-reactive protein, an inflammation marker predicting cardiovascular disease. Eur J Clin Nutr. 2009 Aug;63(8):921-33.

J R Goldsmith, R B Sartor. The role of diet on intestinal microbiota metabolism: downstream impacts on host immune function and health, and therapeutic implications. J Gastroenterol. 2014 May;49(5):785-98.

S M Kuo. The interplay between fiber and the intestinal microbiome in the inflammatory response. Adv Nutr. 2013 Jan 1;4(1):16-28.

J M Harig, K H Soergel, R A Komorowski, C M Wood. Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med. 1989 Jan 5;320(1):23-8.

D M Saulnier, S Kolida, G R Gibson. Microbiology of the human intestinal tract and approaches for its dietary modulation. Curr Pharm Des. 2009;15(13):1403-14.

J Tan, C McKenzie, M Potamitis, A N Thorburn, C R Mackay, L Macia. The role of short-chain fatty acids in health and disease. Adv Immunol. 2014;121:91-119.

P V Chang, L Hao, S Offermanns, R Medzhitov. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2247-52.

R Peltonen, J Kjeldsen-Kragh, M Haugen, J Tuominen, P Toivanen, O Førre, E Eerola. Changes of faecal flora in rheumatoid arthritis during fasting and one-year vegetarian diet. Br J Rheumatol.1994 Jul;33(7):638-43.

Quote

 

When certain gut bacteria infiltrate the rest of the body, our immune system picks up on them by sensing fragments of their cell walls, known as muropeptides. Our molecular detectors for these muropeptides, proteins called Nod2, coat the surfaces of cells involved in the body’s first line of defense. Ilana Gabanyi, a neuroimmunologist at the Pasteur Institute, wanted to know whether these molecular detectors also exist in the brain’s nerve cells.

Gabanyi and colleagues started with genetically engineered mice: Some were designed to lack Nod2, and others were engineered to produce a fluorescent tag that marked wherever the molecular detector was made. The first evidence that muropeptides influence appetite came from the mice without Nod2. Compared with regular mice, these rodents gained extra weight as they aged. That suggested, Gabanyi says, that the muropeptides may provide a “full” signal to the brain that is absent in Nod2-free mice. Because food can stimulate microbes in the gut, eating likely induces the release of muropeptides, she adds.

 

https://www.jyi.org/2016-august/2017/2/18/feeding-your-gut-bacteria-may-be-the-next-step-to-curbing-your-appetite

says inulin, but chicory root inulin never reduced mine...

And I thought PPARα was mostly good.. it is activated by fibrates... [NOT PPAR-gamma].

The propensity of the evidence is still pro-PPAR - I don't agree with fireinabottle in what's good/bad - he just maps the pathways more clearly than anyone else