An alternative to vitamin D supplements?

Screen Shot 2013-02-10 at 11.51.13 PMMy recent post on Why I don’t take vitamin D supplements generated a lot of interest and a few misconceptions.  In that article, I did not suggest any practical alternatives to taking high dose vitamin D supplements.  Here I will suggest a way that may provide the benefits of vitamin D without popping any pills, spending all day in the sun, or ingesting copious amounts of fish.

Some readers got the idea that I believe vitamin D is not beneficial, and that I discount the evidence from studies that show the benefits.  I want to dispel that notion.  I do acknowledge the key role that vitamin D and the vitamin D receptor (VDR) play in bone mineralization and regulation of  innate and adaptive immunity, and among other things.  I further acknowledge that many (but certainly not all) studies support an association between higher vitamin D3 levels and reduced incidence of diseases such as cancer.

As I wrote:

Nobody doubts the important role of vitamin D in the body. But are higher levels of a hormone like vitamin D–whether or not provided as a supplement– always a good thing?

My doubts are focused on several points:

  • Under-appreciation of the fact that vitamin D is a hormone with diverse and dose-dependent systemic effects, still not fully understood
  • Misleading  claims that vitamin D supplementation is “equivalent”  to vitamin D from sun exposure. While the two forms are chemically identical, levels of vitamin D3 synthesized from sun exposure are self-limiting due to feedback regulation.  What happens when we chronically exceed natural limits?
  • Inadequate attention to the possible effects of chronic vitamin D supplementation on homeostatic down-regulation of the VDR receptor. See this discussion bv Dr. David Agus of USC medical school.
  • Inadequate study of the possible long term adverse effects of chronic vitamin D supplementation. Few studies look beyond 4 years. Hormone replacement therapy was in favor for 50 years before the risks came to light . Things don’t necessarily look any more promising when synthetic hormones are replaced bioidentical hormones.

My article created a dilemma for several commenters. These people acknowledged the risks, but nevertheless cited  benefits they personally experienced  from supplementing with vitamin D–ranging from fewer colds and flu, to relief of autoimmune symptoms, and even lessening of depression.

For these people, a key question remains:

Is there a way to get the benefits of vitamin D supplementation, while avoiding the dependency and risks of taking vitamin D capsules daily for the rest of your life?  While I don’t have a definitive proven answer to that question, recent research leads me to speculate here that there is a promising approach that is within everyone’s reach.

It lies within a powerful natural biological process called autophagy.

What is autophagy?   This term  derives from the Greek roots for “self eating”.  It refers to a process that normal cells in every organism can use to derive energy by breaking down and recycling unneeded or “damaged” components.  Autophagy typically kicks in when a cell is  temporarily deprived of externally supplied nutrients, or subjected to other stresses such as low oxygen, infection and chemical exposure.  In the most common type of autophagy–known as macroautophagy–the cell constructs a special membrane enclosure, called an autophagosome, that floats around inside the cell.  The autophagosome is a kind of miniature recycling factory that detects, engulfs and digests damaged proteins and larger organelle structures.  After trapping the cellular components, the autophagosome fuses with a packet of degradative enzymes, known as a lysosome.  It then degrades these large molecules down to their component amino acids, sugars and fatty acids, which can be used as fuels and building blocks for repair and growth.  This recycling of damaged parts ensures an uninterrupted supply of energy and structural components need by the cell.

Screen Shot 2013-02-10 at 11.58.35 PM

 

But the benefits of autophagy go far beyond fueling the cell, and ridding the cell of useless “junk”. Autophagy’s cellular housekeeping function actively counteracts many of the degenerative processes of aging!

UnknownDamage to cell structures and proteins is cumulative, and if allowed to proceed without correction, it can lead to malfunctioning of cellular processes and the genesis of illness. For example, a diet high in reactive sugars such as sucrose and fructose can glycate proteins, creating cross-linked structures known as advanced glycation end-products (AGEs), Similarly, oxidative stress can damage lipid bilayer membranes. The accumulation of these abnormal molecules has been implicated in the genesis of degenerative diseases such as diabetes, Alzheimers, cardiovascular disease and stroke.  Autophagosomes have also been shown to engulf and remove intracellular pathogens, such as the tuberculosis bacterium. Most intriguing, while autophagy regenerates the viability of normal cells, it has been show trigger the self-destruction (apoptosis) of some cancer cells and other abnormal cells.  In short, regular and recurrent autophagy is a key defense against a range of degenerative diseases.

The vitamin D connection.  What does autophagy have to do with vitamin D, you ask?  In mammals, the vitamin D receptor (VDR) sits at the beginning of a important cascade of biochemical pathways. Vitamin D3 or 25-D, from supplements or cutaneous synthesis, is converted to the active 1,25-D form in the kidneys in response to parathyroid hormone (PTH).  Renal 1,25-D plays a key role in the regulation of bone mineralization and waste excretion. But the VDR is also distributed to widely in cells throughout the body.  After the kidney has converted vitamin D3 (25-D) to the active form of vitamin D (1,25-D) it is transported through the circulation to extra=renal sites by a protein known as vitamin D binding protein (VDBP).  Within the cell, the active vitamin D  interacts with the VDR to provide local control of a range of metabolic functions, including cellular immunity, anti-inflammatory, anti-infective, and anticancer responses.

And recent research indicates that one of the key functions of the VDR is to regulate autophagy!

Studies by several research groups have elucidated this signaling pathways that connect the VDR and calcium metabolism to autophagy. According to Shaoping Wu and Jun Sun at the University of Rochester Department of Medicine,

The signaling pathways regulated by vitamin D3 include Bcl-2, beclin-1, mammalian target of rapamycin (mTOR), the class III phosphatidylinositol 3-kinase complex (PI3KC3), cathelicidin, calcium metabolism, and cyclin-dependent kinase (Table 1). These pathways are critical in host defense and inflammatory responses. Hence, vitamin D3 and autophagy are associated with innate immunity…Vitamin D3 is a major regulator of calcium metabolism. Increased circulating vitamin D3 activates VDR, leading to increased intestinal calcium absorption. In excitable cells such as neurons, calcium is released from the sarcoplasmic or endoplasmic reticulum (ER) to activate calcium-dependent kinases and phosphatases, thereby regulating numerous cellular processes, including autophagy. ER calcium induces autophagy when stimulated by vitamin D3. This process is inhibited by mTOR, a negative regulator of macroautophagy, and induces massive accumulation of autophagosomes in a beclin-1- and ATG7-dependent manner since they are not fused with lysosomes. Vitamin D3 can down-regulate the expression of mTOR protein, thus inducing autophagy by inhibiting the mTORC1 complex.

A review by Høyer-Hansen et al., of the Institute of Cancer Biology at the Danish Cancer Society, elucidates the mechanisms by which vitamin D (“VD” here) induced autophagy selectively target cancer cells:

VD analogs are potent inducers of autophagy in different cell types, and autophagy is crucial for their cytotoxic activity towards cancer cells….[T]he signaling pathways connecting VD compounds to autophagy induction are similar in breast cancer cells and monocytes [7,12]. Autophagy induction in both cell types relies on an increase in [Ca2+]cyt, which could result from VDR-mediated changes in the expression levels of calcium-regulating proteins and the subsequent endoplasmic reticulum stress.

…Autophagy usually exerts a cytoprotective function in stressed cells; however, in EB1089-treated breast cancer cells, the enhancement of the autophagic response by ectopic expression of Becn1 increases cell death… Importantly, 1a,25-(OH)2D3-treated primary monocytes do not show any signs of cell death even though their autophagy response is similar to that observed in cancer cells. Thus, it is tempting to speculate that 1a,25- (OH)2D3-induced autophagic cell death could be specific for cancer cells; if true, this would represent a new cancer-specific treatment.

The Danish group has also shown that vitamin D acts to contain and eliminate the tuberculosis bacterium by inducing autophagy, perhaps providing an explanation for the historical use of cod liver oil and vitamin D as early therapies against TB  before the advent of antibiotics:

In tuberculosis, M. tuberculosis resides in phagosomes and evades host antimicrobial mechanisms by blocking phagosome maturation and fusion with the lysosome. Ultimately, the host must overcome this evasion strategy to destroy the pathogen. Accumulating evidence suggests that this occurs via the autophagic degradation of bacteria-containing phagosomes and the subsequent killing of the bacteria in autolysosomes. Interestingly, a recent paper links the 1a,25-(OH)2D3- and autophagy-controlled antimycobacterial defense-pathways.

They conclude:

Recent data link autophagy to two of the beneficial effects of VD: the induction of cancer cell death and the clearance of M. tuberculosis. This opens the possibility that autophagy could be a general mediator of the health-promoting effects of 1a,25-(OH)2D3. Accordingly, there is a striking overlap among the diseases promoted by VD deficiency and defective autophagy. The new data linking the two health-promoting pathways open an interesting research field that could lead to new options for the treatment and prevention of many common diseases.

All very interesting. But if the vitamin D receptor is an activator of cellular autophagy, with its many apparent health benefits is there a way to activate the process without taking vitamin D capsules or spending all day in the sun?

How to activate autophagy without vitamin D.   While vitamin D is one potent way to turn on the autophagy switch, it’s by no means the only way. Autophagy is a phenomenon that occurs throughout the animal kingdom, not just vitamin D utilizing mammals like ourselves. For example, Morselli et al. have shown that autophagy is a requirement for the demonstrated life-extending benefits of caloric restriction in nematodes, mice, flies and worms.

In fact there are several ways you can naturally activate autophagy in your body.  It turns out that all of them involve one form of hormesis or another:

  • Calorie restriction and intermittent fasting.  In my post on Calorie restriction and hormesis,  I summarized some of the research on calorie restriction in humans, primates and other animals. including the role played by autophagy and other mechanisms.  This is also described in my talk on Intermittent Fasting for Health and Longevity.
  • Brief, strenuous exercise.  A 2012 paper in Nature by Levine et al. in mice found that “Exercise is even faster than starvation” at inducing autophagy… “If you just exercise the mice for 30 minutes on a treadmill, autophagosomes start to form. Thirty minutes of running induces autophagy 40 to 50 percent.”
  • Hormetic stress in general.   A wide range of short term, intense but sublethal stressors have been shown to activate autophagy via a common pathway.  Criollo et al.  showed that multiple stressors, including nutrient starvation and numerous chemicals, trigger the activation of the IKK (IκB kinase) complex, inducing the classical autophagy pathway involving p53 depletion, mTOR inhibition, AMPK and JNK1 activation, and release of the pro-autophagic protein Beclin-1.  How many of the other hormetic stressors we’ve discussed in this blog– such as cold showers–might effectively activate autophagy?

imagesWhy I prefer natural stressors.  So perhaps you might be persuaded you to at least consider trying intermittent fasting and exercise (better yet: fasted workouts) to activate your autophagy. If you are one of those who finds that vitamin D helps reduce colds or asthma symptoms — try skipping meals and snacks, and cut back on carbohydrates and excess protein.  I eat one or two small meals a day, mostly low carb or Paleo, and I can’t remember the last time I had a flu or cold.

But taking vitamin D supplements is so much more convenient, right?  I mean — why go to all the effort to subject yourself to uncomfortable hormetic practices when you can just pop a tiny, inexpensive gel capsule once day?  Or even if you go in for exercise and intermittent fasting, why not hedge your bets and throw in vitamin D supplementation too, just to strengthen the brew?

Ultimately a decision like this is a personal one.  You can read all the studies and science that’s out there, but each of us has a different way of balancing considerations of risks and effort, science and intuition.  I can’t make that decision for you.  But I’ll leave you with one thought:

The human species has existed on earth for about six millions years, mammals for 160 million years. Basic cellular defense and repair mechanisms, including autophagy, have played an essential role in protecting us against degenerative diseases during most of that history.  Real world stressors act broadly and in a varied manner. And we have evolved to experience these stressors in their full variety. As Art DeVany likes to point out, real world stressors have  ”fractal” pattern that keeps our metabolisms guessing. To the extent that vitamin D is protective against these diseases, it is likely because vitamin D activates the autophagy signaling pathways. But as David Agus notes in the video I linked above, vitamin D hits a single node in the signaling pathway. Supplementation protocols provide the same fixed amount of vitamin D, day in and day out.

Our ancestors did not have access to a highly purified, concentrated vitamin D pills to activate their autophagy at a fixed dosage every day.  They did it the old-fashioned way:  they “earned” their autophagy with natural and varied stressors like intense physical activity and more sporadic access to foods (and foods with lower insulin and mTOR activation potential).  And they got their vitamin D from the sun and certain fatty foods — again in a varied pattern.

This old-fashioned way of activating autophagy is a experiment that has been running for millions of years. Chronic, life-long supplementation with high doses of vitamin D is a relatively recent  innovation. Do you want to be so dependent on a single compound you take every day?  What happens if you are away from civilization for a few days without your vitamins?

The choice is yours.

 

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30 Comments

  1. jake

    Three problems with eliminating Vitamin D supplementation.

    Only recently have humans spent most of their time indoors. Because we are indoors so much most of us can not make adequate amounts of Vitamin D we have to supplement.

    The Vitamin D precursor, that produces Vitamin D3, is contained in the first layer of your skin called the epidermis. As you age, your epidermis becomes thinner and thinner, producing wrinkles in your skin. The loss of epidermis also means the loss of precursors that produce Vitamin D from your skin.

    Once you are over 50, serious loss of Vitamin D production occurs, and by the time you are 70, you have lost most of your ability to produce Vitamin D.

    However, if you are a senior citizen you can get adequate Vitamin D if you are willing to wear only a loin cloth, and spend most of your day in the sun. The last time I checked the shopping malls, I saw no senior citizens dressed in loin cloths. However, elderly tropical Hunter Gathers did this, and they probably had adequate Vitamin D for all of their lives.

    Optimizing autophagy is only one of the functions of Vitamin D. Four years ago it was discovered that 32 different parts of the body had Vitamin D receptors. Here is a quote from Dr. Cannell.

    “Vitamin D receptors have been found to be present on intestinal, bone, liver, kidney, blood cells , skin, muscle, heart, pancreas, adrenal, brain, reproductive, lung, pituitary, thyroid, and cartilage tissues as well as on lymphocytes, monocytes, and macrophages (all parts of the immune system) indicating the substantial impact vitamin D has on health and well-being.”

    Reply
  2. Vladimir

    Really disappointing article and I am still not sure how to replace D3 that you seem to suggest? Vitamin D is not synthetic but obtained through irradiation of lanolin from the sheep. I am not sure what the point is about autophagy since D3 is involved in it one way or the other. If you want to understand the role tuberculosis bacteria, you should definitelly check German new medicine and its explanation

    I was taking big doses of vitamin D for psoriasis. When I say big , I mean 1 million units for 15 days. It’s ridiculous when someone takes 10 thousand units and say that that is big when such a dose has no therapeutic value. For me limit was about 15-20 million units until I had to stop taking it for a month at least due to loss of the appetite or general weakness at such level. Anyway, it worked pretty good for psoriasis, not entirely but good enough. So people should definitelly take their own way and listen to their body and little bit less of a rhetoric.

    Reply
    • Todd

      Vladimir,

      Vitamin D3 is indeed produced by chemical conversion of a precursor found in lanolin. This derivation process can hardly be considered “natural”; I would it consider synthetic. The lanolin is extracted, crystalized, chemically converted to 7-dehydrocholesterol, dissolved in organic solvents, then exposed to UV radiation, further purified and concentrated, before filling into capsules:
      http://www.livestrong.com/article/414363-difference-between-vitamin-d-from-fish-oil-lanolin/#ixzz2L6I4sKvQ

      The fact that it is (at least partially) synthetic is not something that really bothers me. It’s the daily dosing of vitamin D3 at high levels that you never encounter naturally.

      Regarding autophagy: It is not the case that “D3 is involved in it one way or another”. Autophagy can be activated by the binding of D3 (or other ligands) to the vitamin D receptor, but it can also be activated independently of the vitamin D receptor. For example, intermittent fasting and intense exercise can activate autophagy with absolutely no involvement of the vitamin D pathway.

      Todd

      Reply
      • Vladimir

        Vitamin D is produced by chemical extraction but you shouldn’t hold against it. Most essential oils are extracted by chemical reactions but it’s still natural . It is exctracted from the fur of an animal and since humans have little to no body hair, this is acceptable to me. The fact is that humans have a vitamin D pathway in the digestion tract that makes digesting it possible. As I said, we can also store a good amount of it as I was taking a million units for 15-20 days before encountering saturation point. The way vitamin D works, it’s imperative to take big doses over a few days and then stopping instead of taking small doses every day. Certainly for any chronic condition, vitamin d taking only works in the bigger than usual dose. I did lots of research about it with regards to psoriasis and other chronic conditions. I don’t recommend any other supplementation generally.

        Reply
    • rosa

      how much is a unit? I started supplementing with 40,000 iu for several weeks working down to 20,000 what is weird I would start to feel so much better and start to lose weight and sleep better that I would get scared and reduce it because I did not want to overdose, now I realize that fear is unfounded, when are vitamins and minerals so dangerous we have to be warned away from them? for the past 1 and 1/2 years experiemeting with dosing and 20,000 iu is about perfect. (by the way did ou mean internation units? I did some research and they said that they found toxic levels over a 3 week period as 1,000,000 iu. by the way d3 is not toxic if you are eating a high quality diet of natural plant fats like red plam oil with the a and e in it, these work with d. sometimes I think we confuse healing crisis with disease and feel the vita ormineral or supplement we are taking is overdosing or not working or is becoming toxic I realize this is unfounded. real butter is good for the a, thse balance out d. so I have read. when I would lose weight by the typical method reduced calorie way I never suffered any healing crisis and when I started to eat liberally and healthier with more nutrient density I would get sick but came to realize this was a healing crisis, when your famining weight off you do not heal as your malnourished and cannot afford it so you damage your body without realizing ituntil down the road you have dieted yourself sick. your body will lower the thermostate and reduce use of sugar in the cells I would imagine since sugar is to hard to use without adequate d, a, k cholesterol sulfate and fatty acids to protect sensitive cytoplasm. os your sugar goes up and fatcells go up to compensate and suck up that sugar go make fat that the cells can use without needing all those nutrients we refuse ot eat because we want to lose weight or avoid excess weight because we do not understand how our bodies work.

      Reply
  3. Ugur Gundogmus

    Great article, Todd.

    I understand you are not against vitamin D supplements. However, you want people to choose more natural ways and I think this is a very noble approach.

    I live in Canada and we don`t have enough sunshine in winters. That`s why I take vitamin D in winter months.

    I have a quick question for you: Since you don`t take vitamin D supplements, did you consider having a test in order to learn if you have healthy vitamin D levels?

    Reply
    • Todd

      Ugur,

      You mention that you don’t get enough sunshine in winter to achieve “healthy” vitamin D levels. Did you previously experience any illness or problematic symptoms before taking vitamin D, that are now corrected? Or are you basing this upon the new health standards for optimal vitamin D levels?

      In 2009, my vitamin D3 level (25(OH)-D) was measured at 24 ng/ml. My doctor indicated this was “low” on the basis of studies that consider the lower limit of 32.0 ng/mL to be a threshold for optimal health. So I started taking daily 1000 IU D3 capsules. In 2010, my D3 had increased to 52 ng/ml, which is considered to fall within the optimal range. But I noticed absolutely no difference. I’ve had almost no colds or flus for a decade and don’t have any other complaints. I don’t have asthma or autoimmune disease. My heart health and brain health appear to be good. And I notice no difference in this pre- vs. post-supplementation. That doesn’t prove that vitamin D was not having some kind of protective effect. But as I looked into it, the case for daily supplementation appeared to be weak, so I stopped taking it. I haven’t re-checked my vitamin D level, but it doesn’t concern me even if it dropped back down to 24. It would concern me if it became low enough to indicate issues with bone health, which occur well below 24 – I think around 15 ng/ml. But the new standards of >32 for “optimal health” are questionable to me.

      The whole point of my two articles are to question whether the case has been made for supplementing with vitamin D for the rest of your life, and to propose that at least some of the hypothesized long term benefits of high dose vitamin D result from a downstream pathway (autophagy) that can be activated in different ways.

      Todd

      Reply
      • rosa

        I am wondering todd if the fact you did not experience any difference is because your deficiency was not causing symptoms just yet but underlying damage was being done. I mean had your levels stayed there a few more years you might start to manifest symptoms of a problem, of course doctors do not know what optimal really is only the one who created us knows how much is good or bad for us.

        Reply
  4. Ugur Gundogmus

    Hi again, Todd.

    I had a vitamin D test last week and I just got the results: 32.0 ng/L. Interestingly, my doctor told me to get 1000 IU D3 daily just like you did in the past. What a coincidence!

    You are right about the new “optimal vitamin D levels”. It`s something new and we don`t know if it’s really the right approach or not.

    As for autophagy, I try to fast once a month (36 hours. I started doing it 3 months ago and I feel very good. I didn`t have any problems so far.

    Reply
  5. Tim

    This is the worst article ever. Lots of animal studies and a blanket statement for all humans based on your particular labs.

    I live in Alaska. The sun never gets above 50 degress high in the sky. My wife and I both had Vit D levels under 15 (her’s was 7). We both had bone pain and a host of ills completely cured by 10,000IU/day.

    If I was new to this, and read your article first, I’d still be in the throes of rickets.

    Reply
    • Todd

      Tim,

      I never said that vitamin D supplementation isn’t helpful in certain circumstances. (Re-read the first several paragraphs of what I wrote). And I fully acknowledge that the benefits can be immediate and substantial. No question about that. Vitamin D does modulate an overactive immune system. But rapid relief is not an argument for life-long supplementation. What you are overlooking is that sustained use of a hormone — every day for the rest of your life — may be setting you up for other problems. Prednisone is a powerful steroid hormone that similarly will resolve autoimmune and inflammatory problems, but it is a blunt weapon that will cause other problems with sustained use.

      If you don’t believe there are downsides to chronic supplementation with vitamin D, that’s your choice. But there are many who have had negative health effects from CHRONIC (not short term) vitamin D supplementation. What I’ve provided in my article is some insight in how we might obtain the beneficial effects of VDR activation, without the negative side effects of chronic vitamin D supplementation.

      There is also a big difference between supplementation to get your vitamin D levels above the minimum needed for healthy bone formation, and what is proposed for “optimum” immune health. A vitamin D level of 7 is extremely low and no doubt you were right to supplement. But that is far different than targeting levels above 35 or even 50. The same compound — vitamin D — serves multiple functions, and the evidence for “deficiency” should be considered relative to these different functional ends, e.g. bone health vs. generalized innate immunity.

      Todd

      Reply
  6. This article has a lot of valuable information. The title is what drew me to continue reading. My sons pediatrician has been prescribing ‘Vitamin D’ drops because I was told breastfed babies don’t get enough ‘Vitamin D’ naturally. Obviously, I will continue to give my son what the Dr. prescribes but this new information piqued my interest. I’m wondering if there are potential side effects for infants who are supplementing this Vitamin. Overall, I thought you provided a lot of interesting points. Keep up the good work!

    Reply
  7. king of the monkey bars

    To supplement or not to supplement. The media: books, magazines, blogs, promote or denounce each and every dietary additive. I was told after 50 some people don’t metabolize B12 efficiently, so I take a pill. Does it help? Did I really need to start. I was advised to take D supplements by my doctor after my last physical because I too had a level of 24 ng/ml and mentioned I worked nights. Interestingly in past physicals it was never brought up. I feel ok, but one becomes caught up in wondering whether the “experts” are right. Should I listen to Dr. Oz, or Gary Null? I like the idea of just working out and eating in moderation. Why has the simple act of living become so complicated?

    Reply
  8. Brian

    Just a quick note – I think you were referring to parathyroid hormone rather than pituitary hormone in the following statement: “Vitamin D3 or 25-D, from supplements or cutaneous synthesis, is converted to the active 1,25-D form in the kidneys in response to pituitary hormone (PTH).”

    Reply
    • Todd

      Brian,

      Thanks for catching the error, which I’ve now corrected!

      Todd

      Reply
  9. Brian

    ” I eat one or two small meals a day.”

    Todd,

    This may not be the place for this discussion, but I have just started trying to adhere to a low-carb diet (Low-insulin diet). I was at what I would consider the upper end of a healthy body habitus, but did desire to become more lean. I have lost a considerable amount of weight in just a short time. I am beginning to wonder how I am going to be able to get enough calories to maintain my weight, once I achieve the desired weight/lean status. I am curious how you are able to maintain your weight. What does “one or two small meals” consist of?

    Reply
    • Todd

      Hi Brian,

      My one or two daily meals are generally low carb or Paleo type meals – meats, fish, eggs, cheese, nuts, lots of green or brightly colored vegetables, occasional fruit. I also eat bread and some pastry or dessert now and then. I drink only water, tea, coffee, wine, beer, sometimes milk. No sodas or fruit juices

      My appetite is good and self regulating. I enjoy eating but am readily satisfied with small meals. My weight stays fairly constant. I love to run, bike and rock climb.

      You might want to get a copy of Art DeVany’s New Evolution Diet for tips.

      Todd

      Reply
  10. You can’t know how many other mechanism’s of action Vit D works by. Taking care of one mechanism doesn’t mean you can replace it. Every type of hormesis you mention also has risks and causes damage. I’ve personally not done well with any of them and the more I research the more I understand why. For example, cold thermogenesis can lead to heart disease.
    http://www.sciencedaily.com/releases/2013/07/130702123352.htm

    CR, fasting and prolonged exercise have their own problems. Hormesis is a useful tool, not a panacea, which is something you’re trying to make it out to be.

    Reply
    • Todd

      Joe,

      A few points in response:

      1. This is one of my more speculative posts, as I hope was made clear by phrasing the title as a question and using words like “speculate” and “may”. The idea of this particular post was to highlight an intriguing connection between the VDR and autophagy — to stimulate thinking.
      2. The connection I’m highlighting is not with hormesis in general, but with those forms of hormesis that activate autophagy, such as short term fasting and exercise. There are independent reasons for considering periodic autophagy as a beneficial process, e.g. in removing glycated proteins, upregulating brain BDNF, etc.
      3. Despite the strong overlap between autophagy and the pathways activated by the VDR, your point is well taken that vitamin D metabolism is complex and cannot be replaced one-for-one by autophagy or related pathways. This point, however, should also be acknowledged by those who see vitamin D supplementation an unqualified good without undesirable side effects.
      4. Of the various forms of hormesis I connected with autophagy, I didn’t specifically call out “cold thermogenesis”. I’m not aware of any connection between the cold and autophagy. In other posts, where I’ve advocated brief exposures to cold, e.g. cold showers, I didn’t take this to the point of sitting around in cold vests for hours, as advocated by those who use the term “cold thermogenesis”, such as Jack Kruse.
      5. The article you cited is interesting. But a close read indicates that it was conducted on mice, not humans, and on a strain of mice with genetic tendency towards atherosclerosis. And they were exposed to chronic cold, not intermittent cold. So there are a lot of caveats to consider in drawing conclusions from that study. As the authors note:

      For healthy human individuals without preatherosclerotic lesions, cold-induced BAT activity is probably beneficial for health improvement. In supporting this hypothesis, cold exposure of genetically manipulated healthy mice did not increase plasma LDL cholesterol levels due to upregulaation of Ldlr and ApoE, both involved in high rates of cholesterol clearance. The same is probably true for healthy humans. Patients with preatherosclerotic lesions may have to pay a “high price” for their health when exposed to cold living in a cold climate.

      6. Hormesis, as we all know, involves a dose response. As with any stress, too much of a good thing is toxic or even dangerous. So of course the other stressors you cite — exercise, fasting, CR — can all have serious negative effects if you overdo them. That doesn’t take away from the fact that most people could benefit from occasional short fasts and periodic exercise, even strenuous exercise. The wise person will consider their health status. Someone with hypoglycemia, atherosclerosis or other impairments obviously should not attempt exercise or food restriction in the manner that a healthy person could find beneficial.

      So yes, hormesis is not a panacea. It is a useful tool that can be quite powerful if understood in context. It is also an underappreciated tool, of which few people are aware. So the point of my blog is not to push a panacea but rather to illuminate an underused tool.

      Reply
  11. Oliver

    No mention of Vitamin D derived from food sources such as mackerel, salmon, cod, etc. From my research they pack a decent punch of vitamin D. Thoughts? I’m all for saving my money on supplements wherever possible.

    Reply
  12. Oliver

    Also what about ultraviolet beds, do you think they produce any substantial amounts of D?

    Reply
    • Todd

      Oliver,

      Your questions assume that you need more vitamin D than you are already getting. The point of my article is to challenge the assumption that higher vitamin D levels are a cause — rather than a consequence — of good health. To the extent that modest vitamin D intake is helpful, then I would certainly favor getting it from whole foods like fatty fish — but also vegetables like kale — where it is complexed with vitamins A, K and countless other minerals and covitamins which we don’t yet fully understand. In my previous post on “Why I don’t take vitamin D supplements“, I wrote: “Certainly, it is important to have at least an adequate level of D3 entering the liver, by eating foods rich in vitamin D, and through biosynthesis from adequate exposure to sunlight.”

      Should you use tanning beds to boost vitamin D? The jury is out on that. Tanning beds do boost vitamin D levels and bone mineral density, but there are risks related to melanoma:
      http://healthpsych.psy.vanderbilt.edu/2009/TanningBeds.htm

      Incidentally, while I do not supplement with vitamin D or go out of my way to deliberately boost my vitamin D levels (which was 24 when last tested), I had my bone mineral density tested this week. My T-score of 2.0 is in the 99th percentile for men my age. I also never get colds, flus, infections and have no autoimmune or respiratory conditions. I think that getting an adequate amount of calcium and vitamin D in a generally low carb / Paleo / whole food diet, combined with exercise that stresses bones, is the key. If you take calcium and vitamin D supplements on top of a poor diet and don’t exercise, those nutrients are essentially wasted.

      As I said in my recent talk on supplementation: You are not what you eat, you are what your body does with what you eat!

      Todd

      Reply
  13. Oliver

    Thanks todd.

    “Your questions assume that you need more vitamin D than you are already getting”

    Yes it does, simply because i spend most of my time inside as most people do unless you have a job outside. And you live outside :) also i’m from the uk where sun is hit and miss. So would you say I’m wrong to assume i’m not getting enough? Don’t get me wrong, if i lived in hotter parts of the world i’d be brown as a chocolate bar because i love laying in the sun, but i have to look at it based on reality.

    Reply
    • Todd

      Oliver,

      I’m lucky enough to live in California where we do get a lot of sunshine — admittedly more than you get in the UK. While sunlight has many obvious health benefits beyond natural vitamin D production, I question how much vitamin D you really need — beyond what you can get through a balanced diet. There are plenty of people and cultures that thrive and are healthy even in northern climes like the one you live in. Lots of sunlight is a blessing but not a necessity.

      Do you have any hard evidence that your health is suffering in some concrete way? Do you have good bone mineral density, relatively few colds, flus and infections? Absence of asthma or autoimmune disease? If your health is good in those respects, then I would not obsess about some vitamin D3 metric that is currently in fashion. And if you do have have issues with bone density or infections, vitamin D levels are not the only thing to look at. Switching to a non-inflammatory low carb or paleo diet and adding resistance exercise may do more for you than a supplement. How you eat and exercise has a profound influence on what your body DOES with the vitamin D and calcium it gets, What you put in your mouth can only help you if it is properly absorbed and put to the right use.

      Reply
  14. Oliver

    I hear you. Sometimes i look at these supplements as insurance policies. I feel that bit safer and well-off by taking a little of what science seems to back up.

    Out of interest, even if sporadically, do you take any supplements at all? Like probiotics after a bout of diarrhoea or course of antibiotics or some vitamin d in the winter months, or whey after your workout or when on the run, etc? Or are you 100% strictly diet, exercise and good sleep?

    Reply
    • Todd

      Oliver,

      Orthodox physicians and the Vitamin D Council want you to think of vitamin D (and other vitamins) as an insurance policy — something you use routinely to supposedly prevent a condition or deficiency that you do not appear to have — but might possibly acquire in the future. This approach is unwise because it ignores the known harms — the downregulation of endogenous defenses that results from routine supplementation. I would only take supplements in cases of proven acute symptoms of deficiency (infection, allergies, low bone density etc.) – not just blood levels, but real symptoms — and I would only take the supplement as long as it takes to correct the problem.

      While I don’t take supplements, I do take hormetins — compounds that don’t purport to address purported deficiencies, but instead stimulate endogenous defenses. Most hormetins can be obtained as foods (phytonutrient rich vegetables and fruits, bitter herbs, green tea etc). I do periodically take an oral hormetin that contains cur curcumin and other Nrf2 activators, marketed as Protandim. I take it sporadically, not every day.

      Todd

      Reply
      • rosa

        not an expert but don’t think you have to worry about downregulation with viatd3 it gets sequestered into fat tissue and in fact I am inclinded to think downregulation is a unfounded fear because our bodies know what to do with them getting rid of them is one option, lowering your appetite for various foods that contain nutrients your already heavily doesed with, I found after taking vitac, some bs and other minerals in excess of rda (because I was dealing with not feeling well like getting the flu near my monthly)my appetite for salt, and certain foods went down and my desire for veggies like broculli and lettuces of various types went up and my appetite for fruit went way down, veggies like this are loaded with nutrients that detoxify and eliminate excess stuff. even my desire for whole grains, fruit and sugary stuff went way down (this is a new sensation for me as I never had a reduced appetite that went longer than a day or two. I was always fighting a ravenous appetite (because I have/had been brainwashed to believe I needed sheer willpower to eat less exercise more for weight loss I would try to stick to a reduced calorie diet and exercise program in some way or another)now I know better.

        Reply
  15. I think, that you are mistaken. i can defend the position. Write to me in PM, we will discuss. orthomol vitamin c dosage

    Reply
  16. Stephen

    What are your thoughts on being exposed to ultraviolet radiation as a form of hormesis? For example, sun bathing.

    Reply
    • Todd

      Stephen,

      Sun exposure is a great example of hormesis. UV radiation is beneficial–even essential–at low to moderate doses, while damaging and even dangerous at high doses. As with all hormetics, “the dose makes the poison”. What is typically not adequately considered in studies of the damaging effects of UV radiation is the rate of tanning and the effects of gradual tanning on preconditioning the skin. Moderated exposure to UV promotes synthesis of vitamin D in its most useful form, and has other benefits. Slathering on high SPF lotions deprives you of these benefits. Gradual tanning is the best defense against sunburns, and burning is the real culprit in skin damage and skin cancer:

      http://www.skincancer.org/prevention/sunburn/facts-about-sunburn-and-skin-cancer

      So, rather than rushing out to get a tan at the end of spring, or fearing the sun — seek out the middle ground. Build up a tan gradually and avoid burning. This is more difficult for those with a fair complexion. But not impossible.

      Todd

      Reply

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