Variability and uncertainty in the numbers - what can we really know?

[brendanhill]

My introduction to CRON diet has been watching Michael Mosley's documentary, reading the Longevity Diet, and perusing these forums and the web.

 

I see a lot of number crunching about vitamins and calories and attempts to optimize these numbers.

 

Yet the more I read, the more variability and uncertainty I see in these numbers:

 

- Different bodies requiring different vitamins (how could a single RDI possibly fit all?)

- Different medical conditions weighting the numbers

- Bioavailability of vitamins varying across food sources

- Absorption of vitamins affected by food combinations

- Vitamin content of a particular food varying across different crops, growing conditions, seasons etc

- Nutritional knowledge changing over time

 

You might say, "Yes, but these numbers are the best thing we currently have to work with". Unfortunately, the degree of variability and uncertainty makes me hesitant to spend any significant time analysing and optimizing as I would have little confidence in the results. Furthermore, there seems to be a giant web of causal interrelations between hundreds of cryptically named micronutrients, forming a giant puzzle which I will never fully unpack and hence hesitant to even explore.

 

Instead, in the face of this uncertainty, it seems sensible to me to adopt a simpler strategy:

 

1) Establish a ~6 monthly biomarker testing framework

2) List the major vitamins to consider, hope the remaining obscure vitamins are encompassed by the new regime

3) Identify which foods have the highest bioavailable content/calorie ratio for each major vitamin (traffic light system?) - eat quite a lot of those (exact numbers be damned)

4) Supplement in areas I have a hunch I'll struggle with

5) Review biomarkers each 6 months, adjust foods or supplements accordingly

 

I would appreciate your commentary on the above, and also to hear your perspectives regarding the sources of variability and uncertainty in the numbers, and whether attempting to optimize over such uncertainty is worthwhile.

 

Regards,

-Brendan

[Dean Pomerleau]

Brendan,

 

The five step strategy you outline is pretty much precisely the approach I employ. You (pretty much) can't go wrong with eating a wide variety of fruits and vegetables, nuts & seeds, legumes, some whole grains & sweet potatoes, then check out what I've had to supplement to avoid deficiencies, as a hint to what you might expect/experience and consider supplementing yourself as a near vegan.

 

BTW, we're not alone as vegan/vegetarian CR practitioners, as our recent poll results suggest - "vegan" is the single most frequent dietary pattern people use to describe the way they eat. Here is the relevant graph:

 

 

Welcome to the club!

 

--Dean

[LizC]

Same here, with some individualized tweaking of supplements, e.g., I take extra B2 and Mg to help prevent migraines even though no deficiency is indicated by bloodwork.

[brendanhill]

Wow interesting. I wonder what attracts vegans to the diet? For me, the ethics of animal treatment and my selfish concerns about longevity and wellbeing are entirely unrelated.

 

Dean can I challenge your strategy in one area.

 

Reading through your analysis of your supplementation strategy suggests to me that you are placing a great deal of weight on precise evaluations of vitamin levels eg. to the point of splitting pills into 6ths to get a precise amount. Similarly I have read tales of others who count out specific numbers of nuts or even fractions thereof.

 

This is exactly the kind of precision I feel I would never have confidence in, for the reasons of variability & uncertainty I described above.

 

What, then, is your motivation for this level of precision in your supplementation strategy?

[Dean Pomerleau]

Brendan,

 

Wow interesting. I wonder what attracts vegans to the diet? For me, the ethics of animal treatment and my selfish concerns about longevity and wellbeing are entirely unrelated.

 

I too am a vegan first and foremost for ethical reasons, but vegan and near-vegan diets are also among the healthiest diets on the planet (although sadly, not necessary FOR the planet, at least based on the foods most of us vegan CR folks eat...), so it makes sense that many CR folks would adopt veganism or vegetarianism.

 

Dean can I challenge your strategy in one area.

 

If that was meant as a (rhetorical) question, the answer is yes of course you can - I like challenges!

 

Reading through your analysis of your supplementation strategy suggests to me that you are placing a great deal of weight on precise evaluations of vitamin levels eg. to the point of splitting pills into 6ths to get a precise amount. Similarly I have read tales of others who count out specific numbers of nuts or even fractions thereof.

This is exactly the kind of precision I feel I would never have confidence in, for the reasons of variability & uncertainty I described above.

What, then, is your motivation for this level of precision in your supplementation strategy?

 

Oh - that's a softball challenge  .

 

First, while I do weigh my food, I'm not one to count out specific numbers of nuts, except when I was eating brazil nuts, which I ate only 1/2 of a nut per day to avoid overdosing on selenium. I recently cut out brazil nuts and switched to supplementing selenium (~0.75 RDA/day as insurance on top of my dietary sources), after finally heeding Michael Rae's repeated warning that selenium levels in even a single brazil nut are too high and too variable serve as a safe and reliable source of selenium. 

 

But on to your main challenge / criticism - my (alleged) splitting of my B12 supplement into sixths and taking 1/6th per day.

 

As documented in this response to Michael about my supplement strategy, unlike Michael (who literally splits the same B12 supplement I take with a knife), I "nibble" what I estimate to be about 1/6th of a tablet per day, so that I spread my consumption of the one tablet over approximately 6 days (+-1 day). A single one of these tablets contains 100 mcg of B12, which is 1666% of the RDA. Even factoring in the requirement to take substantially more than the RDA of B12 if consuming it in a single dose per day, I consider nearly 17x the RDA to be much more than required. And reputable vegan nutrition sources like Jack Norris from Veganhealth.org (also cofounder of one of my favorite charities - Veganoutreach.org) agree. Based on B12 absorption studies (which show massive diminishing returns in absorption of a single dose), he recommends getting at least 10mcg of B12 per day if taken as a single dose. More specifically, Jack says:

 

To get the full benefit of a vegan diet, vegans should do one of the following:

• Eat fortified foods two or three times a day to get at least three micrograms (mcg or µg) of B12 a day or
• Take one B12 supplement daily providing at least 10 micrograms or
• Take a weekly B12 supplement providing at least 2000 micrograms.

I have chosen the middle option. My daily dose of ~1/6th of my B12 tablet provides ~17mcg of B12, comfortably above the 10mcg single daily dose recommendation. But my daily dose is not precisely 1/6 of a tablet, as my nibbles on the tablet vary  .

But I don't leave it at that. Instead, I get my serum B12 tested annually. On this regime, my B12 is consistently in the mid 400s (RR 200-1100) - see my bloodwork table for full history, or my latest bloodwork post for most recent results from a couple weeks ago. But since Serum B12 isn't always good measure of B12 status in vegans (some of whom fool themselves into thinking seaweed or other alleged sources of B12 are effective), I got homocysteine tested in my latest round of bloodwork, to be sure. My homocysteine was 9.2 (RR 0-15), which I was satisfied with. Homocysteine level below 10 is thought to be healthy.

So in short, which I'm careful and meticulous about my supplementation strategy, I don't count on precision in the way you seemed to suggest.

 

Hope that helps clarify.

 

--Dean

[Dean Pomerleau]

On a related note, I stumbled across what I think is an interesting alternative to the B12 supplementation strategy described above. 

 

My wife is pretty much addicted to coffee, and gets headaches when she doesn't get her daily fix - usually from Starbucks. So as a gag xmas gift, I bought these caffeine mints for her from Amazon. I didn't notice when I bought them, but they are also fortified with several B-complex vitamins, including 21 mcg of B12 - which is very close to the daily (single serving) dose I target with 1/6th of the Solgar B12 tablet discussed above!

 

Here is the nutrition and ingredient labels from the mints:

 

 

The caffeine amount is modest at 40mg/mint - equivalent to about 1/2 cup of regular (non-Starbucks!) coffee. I consider caffeine to have short-term beneficial effects for energy and cognition, and at worst neutral effects in the long-term, but probably beneficial effects, at least for overall brain health [0], including staving off generalized dementia [1][2], depression [3] and neurodegenerative disorders including Alzheimer's disease [2][4] and Parkinson's disease [4][5] (although its probably best to avoid creatinine and caffeine together [6]). These positive effects on brain health are one of the main reasons I drink caffeinated coffee, so no problem with taking one of these mints per day from that perspective.

 

As you can see, all of the B vitamins are reasonable doses (when eaten as single serving - i.e. one mint). The B12 is in the form of cyanocobalamin, the same form as the Solgar B12 supplement I've been taking for years. Each mint has less than 5 calories (labelled as 0, which really means less than 5. Actually each mint weighs 900mg, and the first two ingredients, sorbitol and xylitol, have 2.6kcal/g, so each mint is about 2.5 calories). Looking at the other ingredients, I consider sorbitol in small quantities harmless, and xylitol (along with erythritol which these mints don't contain) likely to be helpful for preventing tooth decay. Regarding the final three ingredients, magnesium stearate appears harmless, as does silicon dioxide. I don't consider the small amount of sucralose in a single mint (or half a mint - see below) to likely be a problem for gut health [7], given my copious consumption of prebiotics, and my supplementation with a probiotic. The mints themselves are made in the US, which is nice from a safety / contamination perspective, they are vegan (NB Greg!), and they taste good to boot!

 

The only minor downside I can see is cost - $20 for 120 mints, which works out to $0.17/day. This is lot more than the cost of 1/6th of a Solgar B12 tablet (< $0.02/day). But $0.17 per day isn't out of line with what I spend on other supplements. In fact it is exactly the same amount I spend on strontium per day to protect my bone health. Plus, the mints are easy to cut (or bite!) in half, which will get you almost exactly the recommended single daily dose of 10mcg of B12, cutting the cost to less than $0.09 per day.

 

Michael, I know you've been looking for years for a B12 supplement that comes in small doses, and the Solgar's product is the smallest we've both been able to find. This seems like a viable alternative to me. What do you (or others) think?

 

--Dean

 

--------

[0] Pract Neurol. 2015 Dec 16. pii: practneurol-2015-001162. doi:

10.1136/practneurol-2015-001162. [Epub ahead of print]

 

Effects of coffee/caffeine on brain health and disease: What should I tell my

patients?

 

Nehlig A.

 

Over the last decade, Food Regulation Authorities have concluded that

coffee/caffeine consumption is not harmful if consumed at levels of 200 mg in one

sitting (around 2½ cups of coffee) or 400 mg daily (around 5 cups of coffee). In 

addition, caffeine has many positive actions on the brain. It can increase

alertness and well-being, help concentration, improve mood and limit depression. 

Caffeine may disturb sleep, but only in sensitive individuals. It may raise

anxiety in a small subset of particularly sensitive people. Caffeine does not

seem to lead to dependence, although a minority of people experience withdrawal

symptoms. Caffeine can potentiate the effect of regular analgesic drugs in

headache and migraine. Lifelong coffee/caffeine consumption has been associated

with prevention of cognitive decline, and reduced risk of developing stroke,

Parkinson's disease and Alzheimer's disease. Its consumption does not seem to

influence seizure occurrence. Thus, daily coffee and caffeine intake can be part 

of a healthy balanced diet; its consumption does not need to be stopped in

elderly people.

 

PMID: 26677204 

 

---------

[1] Neurology. 2007 Aug 7;69(6):536-45.

 

The neuroprotective effects of caffeine: a prospective population study (the

Three City Study).

 

Ritchie K(1), Carrière I, de Mendonca A, Portet F, Dartigues JF, Rouaud O,

Barberger-Gateau P, Ancelin ML.

 

Author information: 

(1)INSERM U888 Nervous System Pathologies, Epidemiological and Clinical Research,

La Colombière Hospital, Montpellier, France. ritchie@montp.inserm.fr

 

OBJECTIVE: To examine the association between caffeine intake, cognitive decline,

and incident dementia in a community-based sample of subjects aged 65 years and

over.

METHODS: Participants were 4,197 women and 2,820 men from a population-based

cohort recruited from three French cities. Cognitive performance, clinical

diagnosis of dementia, and caffeine consumption were evaluated at baseline and at

2 and 4 year follow-up.

RESULTS: Caffeine consumption is associated with a wide range of

sociodemographic, lifestyle, and clinical variables which may also affect

cognitive decline. Multivariate mixed models and multivariate adjusted logistic

regression indicated that women with high rates of caffeine consumption (over

three cups per day) showed less decline in verbal retrieval (OR = 0.67, CI =

0.53, 0.85), and to a lesser extent in visuospatial memory (OR = 0.82, CI = 0.65,

1.03) over 4 years than women consuming one cup or less. The protective effect of

caffeine was observed to increase with age (OR = 0.73, CI = 0.53, 1.02 in the age

range 65 to 74; OR = 0.3, CI = 0.14, 0.63 in the range 80+). No relation was

found between caffeine intake and cognitive decline in men. Caffeine consumption 

did not reduce dementia risk over 4 years.

CONCLUSIONS: The psychostimulant properties of caffeine appear to reduce

cognitive decline in women without dementia, especially at higher ages. Although 

no impact is observed on dementia incidence, further studies are required to

ascertain whether caffeine may nonetheless be of potential use in prolonging the 

period of mild cognitive impairment in women prior to a diagnosis of dementia.

 

PMID: 17679672

 

----------

[2] J Nutr Health Aging. 2015 Mar;19(3):313-28. doi: 10.1007/s12603-014-0563-8.

 

Coffee, tea, and caffeine consumption and prevention of late-life cognitive

decline and dementia: a systematic review.

 

Panza F(1), Solfrizzi V, Barulli MR, Bonfiglio C, Guerra V, Osella A, Seripa D,

Sabbà C, Pilotto A, Logroscino G.

 

A prolonged preclinical phase of more than two decades before the onset of

dementia suggested that initial brain changes of Alzheimer's disease (AD) and the

symptoms of advanced AD may represent a unique continuum. Given the very limited 

therapeutic value of drugs currently used in the treatment of AD and dementia,

preventing or postponing the onset of AD and delaying or slowing its progression 

are becoming mandatory. Among possible reversible risk factors of dementia and

AD, vascular, metabolic, and lifestyle-related factors were associated with the

development of dementia and late-life cognitive disorders, opening new avenues

for the prevention of these diseases. Among diet-associated factors, coffee is

regularly consumed by millions of people around the world and owing to its

caffeine content, it is the best known psychoactive stimulant resulting in

heightened alertness and arousal and improvement of cognitive performance.

Besides its short-term effect, some case-control and cross-sectional and

longitudinal population-based studies evaluated the long-term effects on brain

function and provided some evidence that coffee, tea, and caffeine consumption or

higher plasma caffeine levels may be protective against cognitive

impairment/decline and dementia. In particular, several cross-sectional and

longitudinal population-based studies suggested a protective effect of coffee,

tea, and caffeine use against late-life cognitive impairment/decline, although

the association was not found in all cognitive domains investigated and there was

a lack of a distinct dose-response association, with a stronger effect among

women than men. The findings on the association of coffee, tea, and caffeine

consumption or plasma caffeine levels with incident mild cognitive impairment and

its progression to dementia were too limited to draw any conclusion. Furthermore,

for dementia and AD prevention, some studies with baseline examination in midlife

pointed to a lack of association, although other case-control and longitudinal

population-based studies with briefer follow-up periods supported favourable

effects of coffee, tea, and caffeine consumption against AD. Larger studies with 

longer follow-up periods should be encouraged, addressing other potential bias

and confounding sources, so hopefully opening new ways for diet-related

prevention of dementia and AD.

 

PMID: 25732217

 

-------

[3] Curr Pharm Des. 2015;21(34):5034-40.

 

Coffee and Depression: A Short Review of Literature.

 

Tenore GC(1), Daglia M, Orlando V, D'Urso E, Saadat SH, Novellino E, Nabavi SF,

Nabavi SM.

 

Author information: 

(1)Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49,

80131 Napoli, Italy. giancarlo.tenore@unina.it.

 

Coffee is among the most widespread and healthiest beverages in the world. It is 

known to be a highly rich source of biologically active natural metabolites which

possess therapeutic effects (i.e. caffeine) and functional properties (i.e.

chlorogenic acids). Therefore, coffee can be considered a drink which has

different positive effects on human health such as cardioprotective,

neuroprotective, hepatoprotective, nephroprotective, etc. However, heavy coffee

consumption may be related to some unpleasant symptoms, mainly anxiety, headache,

increased blood pressure, nausea, and restlessness. During the past two decades, 

several studies have indicated that there is a close correlation between

consumption of coffee and incidence of depression. In addition, phytochemical

studies showed that caffeine is the main responsible constituent for

antidepressant effects of coffee through multiple molecular mechanisms. The aim

of the present paper was to collect the latest literature data (from 1984 to

2014) on the positive and negative impacts of coffee consumption on the major

depressive disorders and to clarify the role of bioactive constituents of coffee 

in the related different clinical trials. To the best of our knowledge, this the 

first review on this topic.

 

PMID: 26303345

 

--------

[4] Life Sci. 2014 Apr 17;101(1-2):1-9. doi: 10.1016/j.lfs.2014.01.083. Epub 2014 Feb

13.

 

Using caffeine and other adenosine receptor antagonists and agonists as

therapeutic tools against neurodegenerative diseases: a review.

 

Rivera-Oliver M(1), Díaz-Ríos M(2).

 

Caffeine is the most consumed pychostimulant in the world, and it is known to

affect basic and fundamental human processes such as sleep, arousal, cognition

and learning and memory. It works as a nonselective blocker of adenosine

receptors (A1, A2a, A2b and A3) and has been related to the regulation of heart

rate, the contraction/relaxation of cardiac and smooth muscles, and the neural

signaling in the central nervous system (CNS). Since the late 1990s, studies

using adenosine receptor antagonists, such as Caffeine, to block the A1 and A2a

adenosine receptor subtypes have shown to reduce the physical, cellular and

molecular damages caused by a spinal cord injury (SCI) or a stroke (cerebral

infarction) and by other neurodegenerative diseases such as Parkinson's and

Alzheimer's diseases. Interestingly, other studies using adenosine receptor

agonists have also shown to provide a neuroprotective effect on various models of

neurodegenerative diseases through the reduction of excitatory neurotransmitter

release, apoptosis and inflammatory responses, among others. The seemingly

paradoxical use of both adenosine receptor agonists and antagonists as

neuroprotective agents has been attributed to differences in dosage levels, drug 

delivery method, extracellular concentration of excitatory neurotransmitters and 

stage of disease progression. We discuss and compare recent findings using both

antagonists and agonists of adenosine receptors in animal models and patients

that have suffered spinal cord injuries, brain strokes, and Parkinson's and

Alzheimer's diseases. Additionally, we propose alternative interpretations on the

seemingly paradoxical use of these drugs as potential pharmacological tools to

treat these various types of neurodegenerative diseases.

 

Copyright © 2014 Elsevier Inc. All rights reserved.

 

PMCID: PMC4115368

PMID: 24530739

 

-----------

[6] Clin Neuropharmacol. 2015 Sep-Oct;38(5):163-9. doi: 10.1097/WNF.0000000000000102.

 

Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With

Creatine.

 

Simon DK(1), Wu C, Tilley BC, Wills AM, Aminoff MJ, Bainbridge J, Hauser RA,

Schneider JS, Sharma S, Singer C, Tanner CM, Truong D, Wong PS.

 

Author information: 

(1)*Department of Neurology, Beth Israel Deaconess Medical Center and Harvard

Medical School, Boston, MA; †Department of Biostatistics, School of Public

Health, University of Texas Health Science Center at Houston, Houston, TX;

‡Department of Neurology, Massachusetts General Hospital and Harvard Medical

School, Boston, MA; §Department of Neurology, University of California, San

Francisco, CA; ∥Department of Clinical Pharmacy and Neurology, Skaggs School of

Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO;

¶Department of Neurology, University of South Florida, Tampa, FL; #Department of 

Pathology, Anatomy and Cell Biology, Parkinson's Disease Research Unit, Thomas

Jefferson University, Philadelphia, PA; **Clinical Trials Coordination Center,

University of Rochester Medical Center, Rochester, NY; ††Department of Neurology,

Miller School of Medicine, University of Miami, Miami, FL; ‡‡Parkinson's Disease 

Research Education and Clinical Center, San Francisco Veteran's Affairs Medical

Center, San Francisco, CA; §§The Parkinson's and Movement Disorder Institute,

Fountain Valley, CA; and ∥∥Singapore General Hospital, Singapore.

 

OBJECTIVE: Increased caffeine intake is associated with a lower risk of Parkinson

disease (PD) and is neuroprotective in mouse models of PD. However, in a previous

study, an exploratory analysis suggested that, in patients taking creatine,

caffeine intake was associated with a faster rate of progression. In the current 

study, we investigated the association of caffeine with the rate of progression

of PD and the interaction of this association with creatine intake.

METHODS: Data were analyzed from a large phase 3 placebo-controlled clinical

study of creatine as a potentially disease-modifying agent in PD. Subjects were

recruited for this study from 45 movement disorders centers across the United

States and Canada. A total of 1741 subjects with PD participated in the primary

clinical study, and caffeine intake data were available for 1549 of these

subjects. The association of caffeine intake with rate of progression of PD as

measured by the change in the total Unified Parkinson Disease Rating Scale score 

and the interaction of this association with creatine intake were assessed.

RESULTS: Caffeine intake was not associated with the rate of progression of PD in

the main analysis, but higher caffeine intake was associated with significantly

faster progression among subjects taking creatine.

CONCLUSIONS: This is the largest and longest study conducted to date that

addresses the association of caffeine with the rate of progression of PD. These

data indicate a potentially deleterious interaction between caffeine and creatine

with respect to the rate of progression of PD.

 

PMCID: PMC4573899 [Available on 2016-09-01]

PMID: 26366971

 

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

[7] Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.

Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

Suez J(1), Korem T(2), Zeevi D(2), Zilberman-Schapira G(3), Thaiss CA(1), Maza
O(1), Israeli D(4), Zmora N(5), Gilad S(6), Weinberger A(7), Kuperman Y(8),
Harmelin A(8), Kolodkin-Gal I(9), Shapiro H(1), Halpern Z(10), Segal E(7), Elinav
E(1).

Non-caloric artificial sweeteners (NAS) are among the most widely used food
additives worldwide, regularly consumed by lean and obese individuals alike. NAS
consumption is considered safe and beneficial owing to their low caloric content,
yet supporting scientific data remain sparse and controversial. Here we
demonstrate that consumption of commonly used NAS formulations

[including saccharin, nutrasweet and sucralose] drives the

development of glucose intolerance through induction of compositional and
functional alterations to the intestinal microbiota. These NAS-mediated
deleterious metabolic effects are abrogated by antibiotic treatment, and are
fully transferrable to germ-free mice upon faecal transplantation of microbiota
configurations from NAS-consuming mice, or of microbiota anaerobically incubated
in the presence of NAS. We identify NAS-altered microbial metabolic pathways that
are linked to host susceptibility to metabolic disease, and demonstrate similar
NAS-induced dysbiosis and glucose intolerance in healthy human subjects.
Collectively, our results link NAS consumption, dysbiosis and metabolic
abnormalities, thereby calling for a reassessment of massive NAS usage.

PMID: 25231862

[brendanhill]

I too am a vegan first and foremost for ethical reasons, but vegan and near-vegan diets are also among the healthiest diets on the planet (although sadly, not necessary FOR the planet, at least based on the foods most of us vegan CR folks eat...), so it makes sense that many CR folks would adopt veganism or vegetarianism.

 

Yes, I summarize the arguments for veganism as ethics, then health, then environment. But I find arguing the environmental angle is difficult because everyone seems to have read whatever the most recent "quinoa/lettuce/tofu is bad for the environment/farmer conditions/something emotive" article which muddies the waters.

 

Having read through your clarification about your B12 strategy (thanks!) it seems as though like having met the B12 daily requirements, you are now optimizing on the basis of cost. I'm not sure for the sake of cents per day that I would bother splitting pills unnecessary - but I admire your dedication to the "O" in "CRON" :D

[Dean Pomerleau]

Having read through your clarification about your B12 strategy (thanks!) it seems as though like having met the B12 daily requirements, you are now optimizing on the basis of cost. I'm not sure for the sake of cents per day that I would bother splitting pills unnecessary - but I admire your dedication to the "O" in "CRON" :D

 

No, you've misunderstood. While I do try to be reasonably frugal, my primary reason for avoiding B12 megadosing (or megadosing any other micronutrient, unnecessarily), is all the recent evidence (e.g. beta carotene, isolated vitamin E forms, etc.) suggesting the potential deleterious effects of excessive vitamin / mineral intake. See the preamble to Michael Rae's post about his supplement regime for more information. He's MUCH more well-informed on appropriate supplementation that I am, and he recommends getting as much of one's nutrition from foods as possible, and recommends explicitly against megadosing in general, and for taking only 1/6th of a 100mcg Solgars B12 tablet specifically.

 

So its about health, rather than cost.

 

--Dean

[nicholson]

For both frugality and avoiding over-dosing, I buy the cheapest B12 pills available (lowest cost per mcg) which around here are those containing a ridiculously large amount per pill compared with the size of dose that makes any sense.  Then I crush them to powder and take a very small amount daily.  Since I do eat modest amounts of animal products I don't need to be too strict about supplementation, except for the fact I was once found to be deficient.  But, as previously noted, it appears to be of no use at all to take more than a tiny 2 mcg a day, because no more than that can be absorbed.

 

Rodney.

 

========

 

"The unverified conventional wisdom is almost invariably mistaken."

[Dean Pomerleau]

Rodney,

 

"The unverified conventional wisdom is almost invariably mistaken."

 

I appreciate your tendency to question conventional wisdom when unverified. But you seem to also doubt verified conventional wisdom to a degree that I don't think ultimately serves you or others. Case in point:

 

But, as previously noted, it appears to be of no use at all to take more than a tiny 2 mcg a day, because no more than that can be absorbed.

 

Do you actually read the posts on the threads you reply to? Or better yet, research your statements before making them?

 

I don't know of any evidence suggesting that no more than 2mcg of B12 can be absorbed in a single dose, to say nothing of a single day.

 

Instead what the evidence I pointed to on the VeganHealth.org webpage on B12 dosing shows is that absorption of B12 is greatly attenuated when taken in a single dose greater than 2-3 mcg.

 

It is to account for and overcome this attenuated absorption that taking 10 mcg in a single daily dose or 2000 mcg in a single weekly dose, is recommended. 

 

To correct for serious B12 deficits, daily doses of several orders of magnitude greater than 2 mcg are often recommended.

 

--Dean

[nicholson]

Thank you for that information, Dean:

 

==============

   

"I appreciate your tendency to question conventional wisdom when unverified. But you seem to also doubt verified conventional wisdom to a degree that I don't think ultimately serves you or others. Case in point:

 

"nicholson, on 29 Dec 2015 - 8:31 PM, said:

But, as previously noted, it appears to be of no use at all to take more than a tiny 2 mcg a day, because no more than that can be absorbed.

 

"Do you actually read the posts on the threads you reply to? Or better yet, research your statements before making them?

 

"I don't know of any evidence suggesting that no more than 2mcg of B12 can be absorbed in a single dose, to say nothing of a single day.

 

"Instead what the evidence I pointed to on the VeganHealth.org webpage on B12 dosing shows is that absorption of B12 is greatly attenuated when taken in a single dose greater than 2-3 mcg.

 

===============

 

First let me suggest that VeganHealth.org is hardly the world's authority about anything.  But they do provide a couple of links to some serious stuff.  Some of it (National Academies Press) says:

 

"When large doses of crystalline B₁₂ are ingested, up to approximately 1 percent of the dose may be absorbed by mass action even in the absence of intrinsic factor (Berlin et al., 1968; Doscherholmen and Hagen, 1957)."   Notice the vagueness of the "up to".  So if 1000 mcg is supplemented then we can conclude that not more than 10 mcg would be absorbed - perhaps four or five times the tiny amount the capacity of intrinsic factor would permit from a normal meal.

 

This information is remarkably old and remarkably vague (it reminds me of the use of "up to" marketing claims that no one ever pays attention to), even though it is in the link currently provided at VeganHealth.  And even then it confirms the importance of daily doses, and the very limited usefulness even of doses 500 times greater than the amount absorbable by intrinsic factor.  They do also say that a second meal later the same day might also absorb a similar amount.

 

I would certainly pay attention to a serious source providing much more specific data on the matter, like, for example reports of observed effects in humans:  If 10, 50, 100, 1000 mcg is taken on a given day, how much of it gets absorbed?  And how far would it raise the blood level of the vitamin?  I have never seen this kind of data but it is what we would need to know if we were to have strong conviction we know what we are doing.  Right?

 

My understanding - directly from a medical clinician routinely ordering serum B12 tests - is that the prescription for appreciable/severe B12 deficiency is intra-muscular injections of it - not massive oral doses.

 

Regarding:  "Do you actually read the posts on the threads you reply to?"  Answer:  If they are a mile long, generally just the intro and the 'Conclusions' paragraphs, if any.  Which, for me at least, argues in favor of shorter posts.

 

Regarding:  "[Do you actually] research your statements before making them?"  The vast majority of what I have been posting about lately I researched long ago - meaning over the past fifteen years.  And in most cases, previously posted here about it at the time, and sometimes I refer to those posts.  But no, if a subject is raised that I have researched fairly thoroughly in the past, I do not go about researching it all over again, each time the topic comes up.

   

Rodney.

 

============

 

"The unverified conventional wisdom is almost invariably mistaken."  (And sometimes the 'verified' wisdom too.  That is how science advances.  Newton was only an approximation.  Quantum mechanics overturned the previous orthodoxy.  And LENR may be about to disprove the vast majority of nuclear scientists who seemed to behave as if they thought they knew everything there was to know!  We will very soon see.)  : ^ ))))

[Dean Pomerleau]

Hi Rodney,

 

Yes - it certainly takes a lot of B12 (relative to the RDA) to overcome the attenuation of absorption above a couple mcg per meal or dose, and I certainly wouldn't recommend becoming deficient to the point where really big doses are required to correct it, either via injections or orally - which are both used to treat B12 deficiency.

 

You wrote:

My understanding - directly from a medical clinician routinely ordering serum B12 tests - is that the prescription for appreciable/severe B12 deficiency is intra-muscular injections of it - not massive oral doses.

 

From the National Institute of Health fact sheet on B12:

 

Typically, vitamin B12 deficiency is treated with vitamin B12 injections, since this method bypasses potential barriers to absorption. However, high doses of oral vitamin B12 may also be effective. The authors of a review of randomized controlled trials comparing oral with intramuscular vitamin B12 concluded that 2,000 mcg of oral vitamin B12 daily, followed by a decreased daily dose of 1,000 mcg and then 1,000 mcg weekly and finally, monthly might be as effective as intramuscular administration [24,25].

 

--Dean

 

[24] Vidal-Alaball J, Butler CC, Cannings-John R, Goringe A, Hood K, McCaddon A, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev 2005;(3):CD004655. [PubMed abstract]

[25] Butler CC, Vidal-Alaball J, Cannings-John R, McCaddon A, Hood K, Papaioannou A, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Fam Pract 2006;23:279-85. [PubMed abstract]