Supplement Timing

I had a request to write a post on supplement timing, that is, how time of day or other timing such as with meals, or whether in the fed or fasted state, matters. I practice timing of supplements myself, although the hard scientific evidence for these practices is sparse. Nevertheless, I think reasons and logic make a fairly compelling case for doing so.

Categories of Timing

Timing of supplements can be broken down into various types. Here’s how I would classify them.

1. Time of day, such as in the morning or evening.

2. Fed or fasted. Some supplements may be absorbed better on an empty stomach, others with a meal. Perhaps more importantly, some supplements could abolish the effects of intermittent fasting.

3. Anabolic or catabolic phase. Humans have a strong diurnal rhythm of anabolism and catabolism, and derangement of this rhythm, that is a weakening of the amplitude of these processes, is a prominent cause of aging. Maintaining peak health and slowing aging requires that attention be paid to the rhythm of anabolism and catabolism, so that amplitude does not diminish and these processes continue to operate as they would in young, healthy people. Therefore, if a supplement can either augment or diminish these, one must time the supplements properly to ensure good regulation of our diurnal rhythm that rids us of junk and builds new, better functioning physiological machinery.

Let’s look at each of these.

Time of Day

The late Seth Roberts used to discuss taking vitamin D in the morning. He and a number of his readers reported much better results from doing so, particularly on sleep. The logic of this is that vitamin D is normally produced in the skin by the action of sunlight, and therefore we may be adapted to receiving vitamin D during the daytime. Whether that time is morning or the afternoon may obviously vary, but it seems clear enough that it would not be at night. Vitamin D taken during the day may reinforce our circadian rhythms; taken at night, it may disrupt them, and thus disrupt sleep and any number of other physiological processes.

To my knowledge, there are no scientific studies on whether this effect is real, but it does make sense, and I don’t think anecdotal accounts should be disregarded. Since it’s no great difficulty to take vitamin D at one time of the day or another, I follow this guideline by taking it in the morning.

Another supplement that can be usefully taken according to time of day is magnesium, which in this case should be taken at night. Magnesium promotes relaxation and thus may promote restful sleep. Some readers of mine have reported that magnesium completely cured their insomnia. I follow this guideline also and take 200 mg magnesium citrate right before bed.

Fed or Fasted

This category has some overlap with anabolism and catabolism, since if you have fasted long enough you will be in a state of catabolism, if fed, you are in anabolism.

N-acetylcysteine (NAC) is a supplement that should be taken with a meal. The rationale for NAC is the replenishment of the body’s most abundant and important internal antioxidant, glutathione. NAC supplies cysteine, which is rate-limiting for glutathione synthesis, but glutathione’s other two building blocks are glycine and glutamate, the former an amino acid, the latter derived from one. Older people do not appear to have diminished levels of glutamate, but they do have lower levels of glycine. These components are equally necessary, and if NAC is taken in the fasted state, glycine may be lacking, and therefore no glutathione is synthesized. So if you supplement with NAC, eat some form of protein with it.

Curcumin by itself is readily metabolized by the liver, and for this reason many supplement manufacturers have added piperine, a derivative of black pepper, to their curcumin. Piperine inhibits the metabolism of curcumin. But curcumin is also difficult to absorb from the gut, and a high-fat meal increases absorption greatly. So I take curcumin with a high-fat meal – and since just about all of my meals are high fat, no problem.

I take zinc with meals for a simple reason: it can make me feel slightly nauseous on an empty stomach. Others have reported this to me as well. If it doesn’t do that to you, then no big deal, otherwise, take it with food. I have no problem with it when I do that.

Anabolism and Catabolism

This is perhaps the most important category. If you are fasting for health – as opposed to doing it to lose weight – you do so because fasting increases autophagy, so you don’t want to take a supplement that might hinder that. If in anabolism, that is during the fed state or around workouts, the same holds, you don’t want to diminish it, and you do want to enhance it.

In the fasted state, I take resveratrol, which I avoid around workouts. Resveratrol enhances autophagy and diminishes IGF-1 and mTOR signaling, so it should increase the benefits of fasting. Whether the effects of resveratrol are strong enough to decrease anabolism from a workout is something I doubt, but I think no one really knows, and since it isn’t difficult to arrange my timing, I don’t take it within a few hours, before or after, workouts.

Lithium extends life by promoting autophagy. However, the mechanism by which it does so is independent of mTOR, meaning that it is not connected to fasting or workouts. Therefore I’m indifferent as to when I take lithium.

As we’ve noted many times here, both fasting and calorie restriction promote longevity. But antioxidants may not only abolish the health effects of exercise, but also abolish the health effects of calorie restriction and intermittent fasting. In this regard, vitamin C is the most important antioxidant, so do not take this when fasting or exercising. Vitamin C diminishes or abolishes the radical oxygen species that are important signaling molecules in exercise and fasting, and which signal the cells to upgrade their stress defense mechanisms and to grow muscle. On days that I take vitamin C, I do so long after workouts and when I’m in the fed state.

Whey is the anabolic protein par excellence. When taken before or after workouts, it enhances anabolism by providing a high level of essential amino acids and branched-chain amino acids (BCAAs). At this point, it perhaps goes without saying that it should not be taken when fasting, as it will totally abolish autophagy. Take it around workouts and in the fed state. Perhaps less obvious, if you take either BCAAs or leucine as a supplement, which I do myself sometimes, this will also abolish autophagy. Take these during the fed state if you fast for health.

Creatine I don’t think has an effect one way or another on autophagy or fasting, but as a matter of convenience I add it to my whey shakes and therefore take it during the fed state.

Summing Up

You should be cognizant of whether a particular supplement interferes with intermittent fasting or anabolism or exercise, and take them at the appropriate times. You want to see results from all the hard work you do, whether in the gym or in kitchen avoidance, and some supplements either enhance or interfere with that work. Likewise, you want to sleep well, and also get the most benefit from your supplements.

The supplements above are all discussed at greater length in my book on supplements for men. You can also see a list of recommended supplements on my appropriately named Recommended Supplements page.

If any readers feel that I’ve omitted something, or have questions, by all means let me know.

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51 comments
awesome says March 8, 2015

Thanks for writing this Mangan, it’s something I’ve been meaning to ask you.

I take a multi, a B-complex, folate, vit D, co enzyme Q, omega 3, resveratrol, zinc and magnesium.

I was having the zinc/magnesium at night and the rest 1st thing in the morning. But having read you recently on the effects of anti oxidants blocking autophagy I was unsure what to drop from the morning schedule, or if I’d be better off just taking them all around lunch? I’ve also started on your recommendation taking L-Theanine with my morning coffees – however it is a protein, so will it also affect autophagy? If so how do I get my morning caffeine high with Theanine edge while fasting?

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    P. D. Mangan says March 8, 2015

    awesome, it looks to me like you could take all your supplements in the morning, nothing there to interfere with fasting/autophagy. As for theanine, it’s not a protein but an amino acid of the type not used in building proteins. Mostly it’s the presence of leucine and other BCAAs that stops autophagy. So I think you’re good to go with caffeine, theanine, and fasting. I do that.

    Reply
awesome says March 8, 2015

Great, thanks for that. I was aware that it’s an amino acid, but had no idea re the effects on autophagy. I tried an iced tea/caffeine tab combo this morning to try to wean myself off the 2 coffees with milk that I can’t seem to give up!
I have been taking all the supps with a glass of fibre mix in the am, which certainly helps with feeling full throughout the morning. I’m not really craving for food till at least 1-2pm now.

Thanks again for all the great work you’re doing, you can tell this is a labour of love for you!

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awesome says March 8, 2015

On further reflection, the multi probably contains Vit C, so maybe I’ll shift it to lunch, which is more often than not turmeric seasoned chicken. With what you said above re curcumin being absorbed better in the presence of fat, I might shift the omega 3’s to lunch to go with that. Thanks!

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Sunny says March 9, 2015

What about cod liver oil? When should that be taken?

Thanks!

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    P. D. Mangan says March 9, 2015

    Any time. It might be slightly better absorbed with other foods, especially fats.

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Stephen Werner says March 9, 2015

In addition to supplementing with N-acetylcysteine (GNC’s NAC-600), I also supplement with both of the other two amino acid components of glutathione by adding them in the form of powders to my breakfast whey protein shakes.

Glutamine has a good deal of research into it’s benefits (http://draxe.com/l-glutamine-benefits-side-effects-dosage/ – links to studies found within), so it seems to me that in addition to it’s role in glutathione synthesis, it might well offer additional benefits to have glutamine in excess.

And, since methionine excess is linked with reduced life expectancy, and given that glycine has been shown to aid in the removal of excess methionine, effectively producing results comparable to dietary methionine restriction (Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats http://www.fasebj.org/cgi/content/meeting_abstract/25/1_MeetingAbstracts/528.2:
“Dietary methionine (Met) restriction (MR) extends lifespan in rodents by 30–40% and inhibits growth. Since glycine is the vehicle for hepatic clearance of excess Met via glycine N-methyltransferase (GNMT), we hypothesized that dietary glycine supplementation (GS) might produce biochemical and endocrine changes similar to MR and also extend lifespan.”);
I also supplement with glycine. (So much easier than trying to restrict methionine http://www.aginginterventionfoundation.org/PracticalMethionineReduction.pdf – see table starting on page 3).

In addition, given research on the effectiveness of leucine – not to mention the strong recommendation of no less and authority than P.D. Mangam in his book “Best Supplements for Men’s Health Strength, and Vitality” – regarding the key role of leucine in muscle anabolism and retention, I also add supplemental leucine to my whey protein shakes.

And, as you noted that you do also, I add creatine to my shakes. I also add cocoa powder (largely based on something I read on the internet @ http://roguehealthandfitness.com/muscle-less-fat-chocolate-green-tea-polyphenols/), and theanine (in powder form), since I like the effect it has on me.

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    P. D. Mangan says March 9, 2015

    Great comment, Stephen, thanks for the added info.

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    awesome says March 9, 2015

    Thanks Steven. Years ago I tested high for homocysteine, and started taking folate to counteract that, unsure whether the homocysteine was a causation/correlation thing in the association with elevated heart risks. As homocysteine is a byproduct of methionine metabolism, are you saying supplementing with glycine is a better way to approach that?

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      Stephen Werner says March 11, 2015

      The short answer to that question would be “no”.

      The longer answer is that I do supplement with glycine (and would advocate for doing so) simply because glycine is both a precursor to glutathione synthesis, and also necessary for the glycine N-methyltransferase conversion of methionine (an excess of which has been correlated to decreased longevity) to homocysteine – or, more specifically, S-adenosylhomocysteine (http://ghr.nlm.nih.gov/gene/GNMT).

      Whether of not the formation of S-adenosylhomocysteine is a good or bad thing, I cannot say – only that excess methionine appears to be worse.

      I simple terms, I figure that if I supplement with cystiene (as N-acetylcysteine), I probably ought to be sure that I also have plenty of both of the other two components needed for glutathione synthesis – glycine and glutamine, with the added benefit that excesses of either beyond the amount need for maximized glutathione sysnthesis will serve to provide ample amounts for other processes – like the glycine N-methyltransferase noted above.

      Of course, a large excess homocysteine has been associated with damage to the vascular endothelium, which, in your case, might make glycine supplementation counter-productive.

      If you’re prone to high homocysteine, I’m really not sure which is the worse condition be in – high methionine, or high homocysteine.

      Perhaps another reader might have better insight regarding this.

      Reply
        awesome says March 17, 2015

        Well, the methionine / homocysteine question is certainly a complex one. We need to get Mangan on this.

        It seems both high methionine and high homocysteine are undesirable.
        N – acetylcysteine seems to displace homocysteine from its protein carrier in the blood leading to cysteine and NAC disulphide which apparently have high renal clearance and significantly lowering homocysteine levels. So it doesn’t seem bad to supplement with N – acetylcyseine.

        B6 is required for the transulfuration pathway breaking homocysteine down to cysteine, where it can go on to increase glutathione.

        If the addition of glycine does indeed aid in the breakdown of methionine, then we may be approaching a plan: Supplement with excess glycine, which will help lower methionine; the homocysteine produced can be managed with the supplementation of b6 (b12 and folate remethylate homocysteine back into methionine) and/or the supplementation of N- acetylcysteine, which in addition to lowering homocysteine will aid in the production of glutathione along with the extra glycine we supplemented with earlier.

        I think.

        This article was helpful:http://www.lef.org/Protocols/Heart-Circulatory/Homocysteine-Reduction/Page-01

        Reply
          P. D. Mangan says March 17, 2015

          N-acetylcysteine blocks methionine restriction affects on obesity. http://www.sciencedirect.com/science/article/pii/S0026049512003873
          Another article which I can’t find at the moment showed that NAC abrogates methionine restriction effects on lifespan. That doesn’t mean that NAC is bad, and indeed it extends lifespan in Drosophila (http://link.springer.com/article/10.1007/PL00013199), only that it is not compatible with methionine restriction.

          The study which showed that addition of glycine mimicked methionine restriction used *a lot* of glycine, 3 levels, 4, 8, and 12% glycine. (http://www.fasebj.org/cgi/content/meeting_abstract/25/1_MeetingAbstracts/528.2?s) The 4% level had no effect. At 8% glycine, assuming what they mean is a percent of total calories, on a 2000 calorie diet you’d be taking about 40 grams of glycine. That’s maybe doable, I suppose.

          However, if methionine restriction extends life, why worry about homocysteine? Any excess homocysteine is clearly not doing harm in the animals. It also appears to me that if adding extra B6 means more cysteine, then B6 might abrogate effects of methionine restriction.

          If one is interested in these effects, the most direct route it seems to me is to eat a low-protein diet. It’s been found that effects of CR are due to low protein. That’s not something I personally want to do at this point, but I may consider it later. Finding the optimal protein intake that balances demands of muscle with life extension might be quite a task.

          Anyway, those are my thoughts.

          Reply
          awesome says March 17, 2015

          Thanks for the reply Mangan. As a lifelong lifter I’m not too keen to go low protein, but like you I’m happy to settle for old man gains and don’t really need to dose my body with protein like I’m 17 or on the gear, so I’ll be following you with interest as you wrestle with the ‘optimal’ protein question you posed today. For now I’ll manage the homocysteine, and perhaps look for a protein shake that is low or no Methionine.

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          Rob H says January 24, 2016

          Hi Dennis, I’ve just come across your comment below re NAC supplementation not being compatible with Methionine restriction and I have to admit I’m really confused! As I previously commented, I have just started taking 97% Whey Protein 4 days/ week to break my overnight fast on non fast/ work-out days, mixed with 3g of glycine. My thinking here was that the cysteine in the Whey and the additional 3 grams of glycine powder would work together to provide the 2 rate-limiting constituents of glutathione, whilst the glycine would also be working as a mimetic for methionine restriction. On top of that I though the acute ingestion of pure whey protein isolate would sharply signal to the body that the fast was over and signal that it was time for the anabolic phase to begin.. All good I thought.. Is this not such a good idea after all then? Maybe you could point me to any flaws in my logic? Could it be that the whey and glycine should actually be taken at different points of the day (or on different days entirely) – or alternatively should I up my glycine intake by more than 10 times to 40 grams a day? Seems like that would be a very large amount though! Aagh! Any clarity you could provide here would be greatly appreciated!

          (PS please see below for link to page mentioned in a previous comment re BBC programme ‘Trust Me I’m a Doctor’: this time Michael Moseley is interviewing Valter Longo about meat and protein intake. Longo states that is a pescatarian on a low protein AND low carb diet as he puts it. Which by a process of logic must mean that he is on a high fat diet – unless he is permanently doing CR, which I have not heard him mention before..)

          http://www.bbc.co.uk/programmes/articles/4qrV2sL2nTrx73WX8YJkgwC/is-meat-good-or-bad-for-me

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          P. D. Mangan says January 24, 2016

          It appears that NAC spares methionine, since some of the methionine is used to make cysteine; hence supplying cysteine allows methionine to be used for other purposes. If you’re going to do methionine restriction via adding glycine, it may be that omitting NAC is the way to go. Keep in mind that both BCAAs in the form of a boosted whey product, and NAC as well, have extended lifespan in lab animals, the former in rats, the latter in Drosophila. Yes, it is all confusing; NAC is probably more useful in those who have demonstrated oxidative stress, which is usually the elderly and those with chronic illnesses.

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          Rob H says January 24, 2016

          Hi Dennis, many thanks for your reply – I think I am gaining some clarity now! Very interesting – so by using glycine to restrict methionine, one is ALSO indirectly boosting cysteine – and so supplementing glycine on its own has a potential ‘triple-whammy’ effect of decreasing methionine and also providing the 2 rate-limiting factors for upregulating glutathione (ie direct provision of glycine and indirect provision of cysteine). Now that sounds pretty impressive to me, even more so given how cheap glycine is. Of course that leads to the question, what is the optimum daily dosage of glycine. I’m not sure whether it is 3g or 40g, but I’ll stick with the 3g for now!

          Although I’m not currently taking NAC supplements, I think I will scale back the whey protein isolate again to only after my 3 x fasted workouts/ week, as I understand it to be rich in cysteine and therefore may abrogate the effect of the glycine. I think I learn something new almost every day from your site by the way – your resource is truly amazing! Oh and as a side-note, I was taking whey protein isolate the last few days to break my overnight fast (17 hours) and it seemed to have a strange affect on me: made me quite tense and irritable, yet a bit lightheaded (not great when you are looking after young kids – I’m 45 years old by the way). Almost as if it were raising my cortisol levels. But the effect seemed to persist into the late afternoon, after my late breakfast and lunch.. So I’m quite glad to scale the whey back to only after workouts and stick with the glycine on its own instead..

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          Rob H says January 29, 2016

          Just as an update to my comment below – as well as taking 4g of glycine on its own each evening before bed, I’m now also putting 4g glycine in my whey shake each time I take it (after my fasted workouts). As long as I am keeping the ‘solo’ glycine each evening, I don’t see any harm in adding another 4g to my whey shake in the afternoon: I figure it might help boost glutathione levels a bit higher since glycine + the cysteine in whey seem to be the rate-limiting factors for glutathione production. I would then rely on the ‘solo’ glycine in the evening to assume the role of the methionine restriction mimetic (ie in the absence of cysteine or any other amino acids). Glycine is so cheap and appears to be well-tolerated so it seems a shame not to make the most of that big box of the stuff I now have in my possession! Please do set me right if you don’t agree with my logic here though. Many thanks!

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          Rob H says February 25, 2016

          Hi Dennis,

          Just following up on your comment below: “It appears that NAC spares methionine, since some of the methionine is used to make cysteine; hence supplying cysteine allows methionine to be used for other purposes.” I have been doing a bit of digging, and it appears you are right on the money with this. If you have not seen this already, please have a look at these 2 articles written by Dr Joel Brind who seems to be at the forefront of glycine research: http://180degreehealth.com/glutathione/ and http://180degreehealth.com/diet-inflammation-part-4/

          He includes those methylation diagrams (including methionine/ cysteine etc) which another commenter had asked for which I found extremely enlightening. A few ‘controversial’ points which emerge:
          1.) As Dennis mentioned in his comment below, NAC supplementation is probably not such a good idea other than for very specific poor health conditions such as chronic oxidative stress. This is because NAC prevents excess methionine being cleared (as Dennis mentioned below). Personally, I will be cutting down on whey protein too because of the high cysteine, and relying more on BCAAs + fish/eggs prior to/ following resistance training.
          2.) We all need to be taking at least 8 grams of glycine per day to make up for the inherent deficiency in modern diets. Easy to do with glycine powder taken as a supplement.
          3.) Dr Brind believes that glycine is broken down to glucose during fasting conditions – so I am assuming it is best to take it during the day and not in the evening when it could interfere with the overnight fast.

          Please do have a look at those 2 articles Dennis, I found them to be extremely enlightening, from a very learned man – and I’m sure you will find them useful too. Do let me know what you make of this: I would love to hear your take on this!

          PS I’m eagerly looking forward to your new book – maybe you could have a look at the glycine/ methionine issue as your next project: I feel it’s effects are almost as far reaching as the iron issue you have brought to light..

          Reply
          P. D. Mangan says February 25, 2016

          Thanks, Rob, I’ll have a look at those.

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YogaDoc says March 9, 2015

I think an important addition to this article would be the fact that certain Vitamins are known to be fat-soluble. This specifically refers to Vitamins A, D, E, & K. When supplementing these vitamins it would likely beneficial to ingest them concurrently with a source of dietary fat in order to aid in the their absorption from the gut.

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    P. D. Mangan says March 9, 2015

    YogaDoc, you’re correct. I don’t supplement with A and E, but I do use D and K, and those are better taken with a high-fat meal.

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      YogaDoc says March 9, 2015

      I do pretty extensive blood testing every 3 months. This helps me dial in my dosage of Vitamins D and E especially.
      For instance, on 5,ooo units of D daily intake, I noticed I was still in the middle range of normal. Boosting up to 10k units daily got me to near upper limit of normal based on the labs reference ranges.

      Similarly, for Vitamin E I noticed my levels were about the same depending on whether I was supp’ing with Vit E or whether I was not. I since stopped buying Vit E supps.

      I have a dilemma with regards to Vit K. I typically supp it every day when I take my Vit D.
      But there is no real direct lab test (that I am aware of to test for Vit K levels.)
      So I don’t know how much real benefit I am getting from the dose I am currently taking … or whether it is actually worth the cost.
      Furthermore, I’ve been consciously eating more kimchee and full fat greek yogurt recently (almost daily//every other day.) I know these to be good sources of Vit K …. so perhaps maybe even less likely that I need to supp exogenous Vit K.

      I guess I don’t have a real direct question.
      But these are just some of the things I’ve been thinking about recently and would be curious to hear anyone’s thoughts.

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        P. D. Mangan says March 9, 2015

        I supplement with vitamin K also, and you’re right about the cost. I paid I think over $30 for a bottle of K capsules. However, it comes in 5 mg capsules, and that’s a huge amount, sometimes prescribed for osteoporosis. That amount is way over physiological, and I don’t think we know what effects those amounts have. What i do is, when I make a whey drink, I open a capsule of K and put about 20% of the powder within into the whey. So maybe 1 mg. A capsule will last me over a week. This is just from doing my own off the cuff reckoning. K is difficult to get in food, for instance even grass fed butter can apparently vary tremendously in the K content depending on time of year, type of forage, etc. Yet K has powerful anti-cancer and anti-atherosclerosis effects, as well as promoting strong bones. So I want it in my rotation.

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          YogaDoc says March 9, 2015

          Fantastic response.

          Do you have any good resources you could direct me (and other readers) to with regards to dosing Vit K.

          Specifically — Vit K2 — Menatetranone — which is what I believe I take.

          I will double check at home later, but I think my caps are also 5mg.
          I’ve been doing a daily 5mg pill with my Vit D … but you’re comments re: osteoporosis with supratherapeutic dosing have me a little concerned now.

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          P. D. Mangan says March 9, 2015

          Thanks, YogaDoc. I’ve read scholarly articles on K but at the moment couldn’t really direct you to a solid resource. My source for iffy K levels in grass fed butter was somewhere on the internet. Bruce Ames also wrote something concerning his nutrient triage theory, showing that K was indeed subject to triage, that is, if not enough K is around, some uses for it are preferred by the cells, others go begging. And yes, K2 is what I take.

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          Allan Folz says March 9, 2015

          I’ve been taking Vitamin K for a few years now. As far as I know, there are only 2 or 3 published reports on it. Details are really sketchy. I think one was a study on Dutch adults where the ones that ate the most aged, hard cheese (a source of K2), had the least atherosclerosis. I think another one was a similar population-correlation study in Japan using Natto consumption. The third, and IIRC, the source of the 5mg/day recommendation is from some researchers in Japan or S. Korea that used 5mg/day on a set of geriatric women. I believe it stopped, if not reversed, their osteoporosis. However, 5mg/day is an obscene about of K2 when you look at how much one could possibly get from diet. It’s probably cheaper than the comparable pharmaceutical, but if you don’t need osteoporosis treatment I can’t think of a reason to entertain taking that much.

          Based on my own experiences of paying close attention to plaque growth on my teeth, one 1mg drop of Thorne’s K2 liquid every 3-4 days (ie twice a week) is the sweet spot. I tried one drop once a week and my teeth would sometimes get a little fuzz by the end of the week. Conversely, every other day, doesn’t feel particularly smoother than twice a week. So Wed’s & Saturdays it is. I’ve thought of diluting it further so as to get a daily dose while still averaging 2mg/wk, but have never gotten around to actually doing it. (Is there a supplement for procrastination?)

          BTW, as for Thorne, they use the version, MK4, isolated from dairy. It costs considerably more than the bacterial sourced version, MK7, but it seems something from dairy is going closer to what our bodies would be adapted to. Once I started noticing an immediate and direct difference from taking it (my teeth felt cleaner), I decided to spring for the the “good stuff” from Thorne. The other nice thing about the K2 from Thorne is it’s suspended in an oil so it’s very easy to dose at whatever dosage one chooses. Taking apart capsules is a PIA. I wish all my supplements could be oil drops. 🙂

          It’s also my guess (and completely a guess) that Thorne is the sole producer of MK4 and all the other supplement makers buy from them. I think for a lot of supplements there is one, maybe two factories (or do they prefer to call them plants) and everyone just repackages whatever form they buy wholesale.

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          P. D. Mangan says March 10, 2015

          Thanks, Allan, for both of your comments. It seems like you and I have both read the same papers on K, at any rate I distinctly remember both of those you mention. I have never heard anything about K and dental plaque, any source for that? Plaque is made by action of bacteria, so I’m not seeing how K would help. I get a ridiculous amount of plaque, so much so that I was going to the dentist for cleaning more often than every 6 months, and I cannot for the life of me understand why, given I eat low carb paleo.

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        Allan Folz says March 10, 2015

        “I have never heard anything about K and dental plaque, any source for that?”

        Just my own personal experience. I’ve recommended it to two other people I knew that were complaining of dental problems and they both experienced a big change after supplementing. So, N=3? Wait, Denis Minger makes N=4.

        I am surprised if you’re having plaque problems and also taking K2. At $30 bottle, I’m guessing it’s the Carlson’s? Lots of people seem to take it, but you might try the MK4 oil from Thorne. They have a version diluted with vitamin D if you want to go a little easier on the initial outlay until it’s proven itself. Increase the dosage to get an equivalent of 1.0mg/day and see what happens. In my experience the response was almost immediate, as in a few days to a week.

        I have one more argument in favor of K2 for dental health. A great source for K2 are salivary glands. Who knew? I didn’t until long after I’d discovered how it worked as a supplement. My guess is K2 is used in our salivary glands to create an antiseptic to kill the plaque-forming bacteria on teeth. I also suspect (albeit this is complete speculation) it similarly cleans plaque from our arteries, and that’s why it’s associated with better heart health. Gives credence to the pathogen hypothesis for heart disease. And speaking of pathogens and heart disease, another interesting angle is that I read once a while back that statins were originally developed as antibiotics. It made me wonder if that’s where they get their efficacy; NOT from lowering cholesterol, and which makes sense if we trust the lipid hypothesis is a complete load of bunk.

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Allan Folz says March 9, 2015

About 7 or 8 years ago I overheard some cyclists joking about a recovery drink messing up a buddy’s sleep on account of it being high in vitamin B, but the labeling being a bit less than obvious in that regard. I would occasionally have insomnia and when I heard them joking, a light bulb went on in my head. From then on, I would take vitamin B no later in the day then I would drink a cup of coffee.

For fat soluble vitamins, if it’s convenient for me to take them with a meal, I will, but at the same time, I cannot imagine a few drops of vitamin D or a drop of K2 being more or less absorbed with or without a meal. Cod oil on the other hand, is a much larger volume dose. That I will only take with a meal. Also, it’s high in vitamin D, so that speaks to breakfast, lunch, or the best of both: brunch.

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Braivo says March 10, 2015

This, together with your book on supplements, has helped me tremendously. I can’t say enough about N-A-C and how it has improved my mental well-being. Throwing whey into the rotation has helped me gain 10 lbs of muscle. Keep up the good work.

What are your thoughts on the timing of fish oil? I take prescription fish oil in large doses twice a day for elevated triglycerides, so my morning dose occurs in the fasted state.

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    P. D. Mangan says March 10, 2015

    Braivo, thanks very much, to quote T.S. Eliot, glad to be of use. I think your fish oil (Lovaza?) would be fine in the fasted state, but possibly better absorbed with a meal. One question I have, do you eat low carb? Paleo? Because if you do, and have only recently started, these interventions have a good record of reducing triglycerides.

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      Braivo says March 11, 2015

      I started Lovaza before I went low-carb paleo. The Lovaza alone dropped my trigs to “normal” range, but once I went paleo they plummeted (44 at my last reading). It is likely I could drop the Lovaza now and maintain healthy trigs, my doctor even suggested this yesterday.

      However, I would take fish oil anyway, and with Lovaza covered by my insurance I am getting pharmaceutical grade fish oil for next to nothing. I may experiment with reducing the current 4g dose though.

      Lovaza was a turning point for me, besides lowering my trigs it dramatically improved my mental well-being and cleared up a skin condition I struggled with. I am a bit hesitant to pull back on it, although a high-quality OTC fish oil would likely have the same result.

      Reply
peckerwood says July 29, 2015

Reading this has made me concerned that my morning routine has screwed up my IF. I fast for weight loss. I already have all the muscle I need. I guess I can take a D and a theanine in the AM. BCAA pre-workout (if I get to do a fasted workout that day). I was taking NAC along with my coffee but I will move it to lunch.

Should I take Omega 3 fish oil while fasting? It looks like anti-oxidants are a no for days I work out.

I guess the question is, maybe make a chart for weight loss that clearly spells this out?

Good site, I will have to buy your book.

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    P. D. Mangan says July 29, 2015

    Omega-3 should be fine while fasting, and thanks, I should make up some kind of chart. I’m thinking about revising and expanding my supplements book, which would be a good place for it.

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      Rob H says January 16, 2016

      Morning Dennis, that chart sounds a great idea. Also a chart to show the effects of combining glycine supplementation (and how much for a typical non-obese male) with NAC supplementation, ie how they work together, what the net effects are and whether it would overall be better to just focus on EITHER glycine OR NAC and leave out the other. Maybe the best way forward would be to just rely on the cysteine contained in post-workout whey protein isolate powder (rather than supplementing directly with NAC), combining this with a daily supplement of 40g of glycine powder?? I have tried to draft up a schematic chart myself based on the above comments re NAC/ cysteine/ homocysteine/ glycine/ methionine , but I can’t seem to get it straight in my head!!

      By the way, I bought your current book on supplements a while back and would certainly be interested in buying the sequel!!

      Reply
        P. D. Mangan says January 16, 2016

        Rob, a schematic chart is a good idea, and one of my possible projects is a revision of my supplements book. Some of my thinking on them has changed, and I’ve learned more about others.

        Reply
peckerwood says August 24, 2015

also, if I am doing fasted exercising for weight loss, when -if ever-should I be taking anti-oxidants?

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    P. D. Mangan says August 24, 2015

    Best to take any antioxidants such as vitamins C and E in the fed state, away from workouts.

    Reply
      Rob H says January 23, 2016

      Hi Dennis, There’s a fascinating TV programme showing on the BBC in the UK at the moment called ‘Trust Me I’m a Doctor’ whereby the team actually undertake some (small-scale) but pioneering new research and talk to experts regarding diet, exercise etc. See below for a link to the page regarding a test they did on the benefits of anti-oxidants in smoothies: it appears they are much worse than useless – with the body actually downregualting it’s endogenous supply of antioxidants much more and over a longer period than any beneficial effect of taking exogenous antioxidants. It’s all down to homeostasis – as we presumed.

      This makes me think that it would be a good idea to completely separate out pure ‘free-radical scavenging’ anti-oxidants from the class of ‘hormetic phytonutrients – ie the ones that work by actually slightly poisoning us.. Not sure if this is something you would be interested in posting on, but as a starter for 10, after seeing the above TV programme, I would only want to make sure I got the minimum recommended daily allowance of vitamins C, E and selenium from food – actively trying not to take too much so that I don’t negatively affect endogenous antioxidant production. I can get more than enough from my food for these nutrients (eg berries would cover the vitamin C), so the out-take for me is never to supplement anything purely for its purported antioxidant properties. (By the way, you mentioned in your book that you supplement with Vitamin C: is this one of the things you alluded to that you have since changed your mind on?)

      Then in the other group you have grapeseed extract, alpha lipoic acid, resveratrol, co-enzyme Q-10 which all appear to have beneficial effects of specific regular supplementation – but these benefits are in spite of, rather than because of, any additional anti-oxidant properties they may possess. Would you agree with that dichotomy?

      http://www.bbc.co.uk/programmes/articles/5lcN0WJR5GL98tT6S0B19p4/are-antioxidant-rich-products-good-for-me

      (Unfortunately if you want to actually watch the programme, the BBC iPlayer won’t work outside of the UK, but you might find it posted on YouTube. the link above though contains all the info in the programme itself.)

      Reply
        P. D. Mangan says January 24, 2016

        Hi Rob, the dichotomy between antioxidants (vitamins C and E) and hormetic phytochemicals (resveratrol, etc) is correct. Vitamin C is indeed something I’ve changed my mind on, and I rarely supplement with it anymore – last time I did was when I had a cold. Antioxidants do just what you said – down-regulate the internal antioxidant system. On balance that may not be so bad, because presumably the total antioxidant capacity (external + internal) remains the same of nearly so, but given the effects of external antioxidants on exercise, it seems best to avoid external antioxidants. Although it should be noted that some researchers have failed to find any effect, good or bad, of antioxidants on exercise – it’s still a theory in progress.

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          Rob H says January 24, 2016

          Thanks for confirming back on that Dennis – that’s the only time I take Vitamin C as well now.. Do have a look at the link I sent you above, because what they found was that the total antioxidant capacity does NOT remain the same. After an initial spike in antioxidant status one hour after taking an antioxidant rich smoothie, the serum antioxidant concentrations then fell below the baseline after around 4 or 5 hours. By the time the experiment had finished (24 hours), the level of antioxidants in the volunteers’ blood was only just back to the initial baseline level. If someone repeated that cycle every day then they would be operating below baseline for the vast majority of each day. Far better to look at ways to encourage the upregulation of endogenous antioxidants in my humble opinion!

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          P. D. Mangan says January 24, 2016

          Interesting, I agree that it’s far better to encourage endogenous antioxidants.

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Rob H says January 13, 2016

Hi Dennis, I work out on Monday, Wednesday and Friday lunchtimes, so I avoid taking any antioxidant supplements those days, instead taking them on Tuesday, Thursday and Sunday mornings with my breakfast at 8am. I don’t take them at night, since I don’t want to interfere with overnight autophagy (I also work-out fasted on the 3 days mentioned above, breaking the fast immediately after the workout with whey and then lunch). However, I have recently started taking cold showers every day now at around 7.30am, ie just before taking the antioxidants with my breakfast as mentioned above. My question to you is: will taking the antioxidants just after the cold shower abrogate the beneficial effects of the cold shower? I’m assuming not – as I read in one of your other recent comments that you felt cold showers REDUCED inflammation (which is why cold showers should not be taken around work-outs) – and I believe exactly the same holds true for anti-oxidants, ie that they reduce inflammation? So, putting 2 and 2 together, I’m assuming taking anti-oxidants and cold showers close together should have a complementary rather than an antagonistic effect, since they both serve to reduce inflammation? Please do let me know if you spot any flaws in my strategy – many thanks! I have come to realise that in this area timing is everything – but it is not easy!

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    P. D. Mangan says January 14, 2016

    Hi Rob, in the case of cold showers, they reduce the inflammation of exercise, but if you haven’t exercised, there’s not much inflammation to reduce. Cold showers also activate the HPA axis, but I believe you’ve got to immerse yourself in very cold water to get certain benefits; for instance, winter swimmers (polar bear type) have higher levels of glutathione and antioxidant enzymes, but I rather doubt that a garden variety cold shower will up-regulate these. So, to sum up, I think you’re good to go the way you’re doing it.

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Rob H says January 14, 2016

Great, many thanks for confirming back on that Dennis. This area of timing seems to be so important. It appears to me that one other important category of timing may be that of ‘acute inflammation versus inflammation reducers’. It seems that you want to keep the 2 groups as separate as possible in order to avoid one abrogating the effects of the other. I would therefore put the following into the ‘acute inflammation’ group: high intensity strength training, HIIT training and fasting (which is why I always work out fasted). I’d put cold showers and anti-oxidants in the ‘inflammation reducers’ group. Maybe you can think of others to fit into each category? Not sure if other low-level ‘hormetic’ stressors such as sun exposure and polyphenols would really fit into the ‘acute stressors’ group, as it seems to me their effect is not so pronounced/ acute, maybe more of a chronic effect there if you subject yourself to them regularly.

One other point it’s worth noting, is that only relatively recently did I make the connection that the true anti-inflammatory ‘antioxidants’ are solely the potent free-radical scavengers, ie vitamins E, C, beta-carotene and selenium (I only supplement with selenium from this group). However, I have been taking other supplements touted as being ‘antioxidants’ such as grapeseed extract, alpha lipoic acid, resveratrol, co-enzyme Q10 and NAC – but it seems the benefits of these group are NOT primarily as antioxidants as such, rather they are doing the opposite: causing acute inflammation from which the body then needs to adapt and up-regulate endogenous antioxidants.. Do let me know if I have misinterpreted any of this! Fascinating stuff!

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    Rob H says January 14, 2016

    Maybe that would mean that taking this last group of ‘so called ‘anti-oxidants’ – which are in fact hormetic stressors, not anti-oxidants as such – would actually be BENEFICIAL to add to the acute stress of a fasted workout, and just to avoid vitamins C etc instead, ie the ‘classic’ antioxidants. But I think that assumption goes well beyond the realms of any real-world studies I know of – as so much of this stuff does!!

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    P. D. Mangan says January 15, 2016

    Absolutely correct on the definition of antioxidants, Rob. Virtually all those things referred to as antioxidants in the media are in fact hormetic agents which increase levels of detoxifying enzymes (phase 2 enzymes) via Nrf2, and antioxidant enzymes (superoxide dismutase, catalase, glutathione). (Though from that list, NAC and CoQ10 are not hormetic, not antioxidants either.) Beneficial phytochemicals are all hormetic agents. (Can’t think of an exception.)

    Reply
      Rob H says January 15, 2016

      Thanks Dennis – and thanks for the insight on NAC and CoQ10, I wasn’t aware of that. Constantly learning in this area!

      Reply
markb says February 18, 2016

Hi, PD
Thanks for answering my recent question on iron.
Could you give me your opinion on the following, please?

1.
I take a ‘Life Extension’ brand Vitamin K supplement (2.7mg) three times a week with my early evening meal (alternating days with Vitamin D). The Vit K supp contains 10mg of Vitamin C (as Ascorbyl Palmitate). I’m trying some interventions to reduce iron absorption (teas, dairy, green tea tablets) and also planning on getting some IP6. In your opinion, would the Vit C in this supp be enough to counteract the other interventions? I couldn’t find a clear answer on the web for the dose of Vit C required to increase iron absorption, although I found this:
http://www.ncbi.nlm.nih.gov/pubmed/6940487
I could take the Vit K supp 2 hours before eating or 3 or 4 hours after, if that would make any difference. Switching to a different brand would also be an option, of course. Is 2.7 mg three times a week too much? And would it actually be better to take it at the same time as Vit D? (for some reason I half remember something about keeping them apart, hence the alternate days)

I also like to eat a small orange or similar citrus fruit just after my meal. I’ll probably have to give that up!

2.
Would Taurine (7 grams) and Citrulline Malate (3 grams), both in powder form, taken in the morning, break my fast (i.e. abolish autophagy)? I am taking them pre-emptively, in an attempt to reverse what arterial damage may have occurred from 10 years of cigarette smoking (I quit in early 2009, aged 28). I currently take them not long before my early evening meal. I’ve heard they can be a good pre-workout, as well — so again, morning would perhaps be better. Could you foresee any harm from long-term use of these two supplements?

3. Is IP6 better taken fed or fasted? Or no difference?

Looking forward to the new book on iron, and would also be interested to see your insights on prostate health (you recently mentioned that you were contemplating a post on this).

Reply
    P. D. Mangan says February 19, 2016

    Hi Mark, 10 mg is a small amount of vitamin C, and I’m thinking any effect on iron would be negligible. Re vit K, 2.7 mg 3 x week does sound high. Some of this is necessarily guesswork, but in any case we wouldn’t normally get that much via food. Whether it’s harmful, I doubt it. The orange or other citrus is definitely enough to increase iron absorption, maybe up to 50% or so. Taurine and cirulline: no, don’t see any problem there, either in long-term use and they wouldn’t break a fast. IP6: I take this fasted myself. Since it’s a strong iron chelator, it could get “used up” when taken with food by chelating the iron and copper in the food. That’s not wholly bad of course, and in fact, one could take it both fed and fasted, one to stop iron absorption, one to chelate iron in the body.

    BTW, someone left a link awhile back to a study that purported to show that IP6 wasn’t absorbed from the gut. Since then, I’ve seen a number of studies, human and animal, that indicate that it certainly is absorbed. In mice, for instance, given in their drinking water, it reduces tumors.

    Reply
      markb says February 19, 2016

      Thanks very much for the comprehensive answer, PD.

      Reply
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