Studies Confirm: Natural and Synthetic Vitamins Can Differ in Quantity & Quality of Effects! Vitamins A-E, B's & More

Pills or fruits, one are funky and useless, the other ancient and healthy!?

In a 2000 paper in Medical Hypothesis, R.J. Thiel writes "[t]here appears to be a tendency to label those who profess that natural vitamins are better than synthetic ones as quacks" (Thiel. 2000). No wonder, after all, every good text book will inform future physicians and researchers that the difference between natural and synthetic alpha-tocopherol was a mere quantitative one.

In other words, as long as you make sure that you administer 1.36x the amount of "natural" vitamin E in,   all-rac-α-tocopherol should do the exact same as its natural cousin.

Learn more about the effects of your diet on your health at the SuppVersity

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Dairy Protein Satiety - Casein vs. Whey

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5 Tips to Improve & Maintain Insulin Sensitivity

Carbohydrate Shortage in Paleo Land

Even common sense, should tell us, though, that it is unlikely that a colorful mix of  four vitamin E stereoisomers (SRR, SRS, SSR, and SSS) won't have the same effect as pure RRR-alpha-tocopherol as it can be found in nature. Accordingly, Thiel may be right, when he writes that "[t]his broad brush label may be stifling legitimate nutrition research" (Thiel. 2000). In his paper he addresses several issues, including the often heard claim that the body cannot distinguish between natural and synthetic forms of vitamin E, a claim of which he argues that it is misleading because

• it neglects the effect of different structures on absorption and utilization of vitamins (Schumann. 1997; Vinson. 1988, 1989 & 1999);
• it ignores the size differences between the various isomers that will directly affect the absorption of and bioavailability of the nutrients (Macrae. 1993); 
• it does not seem to consider the fact that "natural" vitamins in the original sense come in a nutrient matrix that will have profound effects on both the absorption & activity and the effects of vitamin E containing foods (and complex supplements | Jenkins. 1994);
• it ignores the fact that most USP vitamins are crystalline in structure (Ensminger. 1993; Macrae. 1993), while most vitamins in food are not (and are actually present in complex carbohydrates, proteins, and lipids | Thiel. 1999)

All this  does not mean that USP vitamins do not have any value (they clearly do), but studies have shown that vitamins in natural food complexes are better than USP isolated vitamins; and here is a handful of examples:

• Vitamin A - As it is the case for many other vitamins, the term vitamin A refers to a whole class of molecules, called "retinoids", which include both retinol and its natural metabolites as well as a large number of synthetic analogues that have structural similarities to retinol but may subserve only some (or none) of the functions of natural vitamin A (Ross. 1999).
  
  

  

  Neural tube & other defects increase sign. w/ high doses of synthetic, but not food-borne natural retinol (Rothman. 1995).

  As Thiel points out, some of the commonly used forms found in synthetic supplements are not naturally found in food (Ross. 1999). Some of them have been linked to liver cirrhosis (Fallon. 1990). More specifically, it has been reported that consumption of more than 10 000 I.U. per day of synthetic vitamin A increased the rate of birth defects, while consumption of natural vitamin A from foods (including betacarotene, a precursor) did not (Rothman. 1995).
  
  Retinyl acetate is the major synthetic form of vitamin A and is a vinyl or coal tar at one or more stages of processing (depending upon the manufacturer) (Hu. 1992). An animal study found that synthetic vitamin A in the form of retinyl acetate significantly reduced vitamin E utilization (Schelling. 1995); this has not been shown to occur with natural vitamin A (i.e. Ross. 1999). An animal study concluded that a natural food complex vitamin A was probably less toxic than a synthetic USP form and was 1.54 times more absorbed into the blood (Vinson. 1989).

Please note: Most of the differences are of quantitative nature, which means that you will have to take more of the "synthetic" version to achieve similar steady state levels. Only in some cases, the effects are qualitatively different. However, in some genetically disadvantaged individuals, who cannot do the conversion that is necessary for e.g. folic acid or pyridoxin (B6), these differences can be qualitative (because the agents don't work at all or, as in the case of folic acid) even break the whole system.

• Thiamin, Vitamin B1 - The free vitamin B1 (called thiamin) is a base. When it is synthesized it becomes a solid salt such as thiamin hydrochloride or thiamin mononitrate (Tanphaichitr. 1994). Synthetically thiamin is usually marketed as thiamin hydrochloride or thiamin mononitrate and is a made from Grewe diamine (a coal tar derivative) processed with ammonia and other chemicals (Hui. 1992). No thiamin hydrochloride (often listed as thiamin HCL) or thiamin mononitrate is naturally found in food or the body (thiamin pyrophos phate is the predominant form in the body (Tanphaichitr. 1994))).
  
  Against that background it's not surprising that an animal study found that a natural food complex vitamin B1 was absorbed 1.38 times more into the blood and was retained 1.27 times more in the liver than an isolated USP thiamin hydrochloride (Vinson. 1989).
• Riboflavin, Vitamin B2 - The free vitamin B2 (called riboflavin) is a weak base. When synthesized it becomes an orange amorphous solid. Some synthetic riboflavin analogues have very weak vitaminic activity (Kanno. 1991).
  
  Animal studies indicate that a natural food complex vitamin B2 was absorbed into the blood and was retained 1.92 times more in the liver than an isolated USP riboflavin (Vinson. 1989).
• Niacinamide, Vitamin B3 - ‘Niacin is a generic term, the two coenzymes that are the metabolically active forms of niacin (are) nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP).
  
  

  

  Peas, peanut(butter), poultry, ... if it starts with "p" it's a good source of niacin ;-)

  Only small amounts of free forms of niacin occur in nature. Most of the niacin in food is present as a component of NAD and NADP nicotinamide is more soluble in water, alcohol, and ether than nicotinic acid. Beef, legumes, cereal grains, yeast, and fish are significant natural food sources of vitamin B3, of which studies indicate that it has a 3.94 times higher absorption rate than synthetic B3 and will be retained 1.7 times more efficiently in the liver than isolated USP niacinamide (Vinson. 1989).
• Pyridoxine, Vitamin B6 - Just like B2 & B3, the USP "vitamin B6", pyridoxine is not the naturally occuring form of the vitamin. It is thus not surprising that the absorption of the "original" is 2.54 times more into the blood and its retention in the liver is 1.56 times higher compared to the USP form (Vinson. 1989).
• Folate, Vitamin B9 - Is one of the few vitamins where many experts acknowledge that its use as a dietary supplement is bogus. No wonder, pteroylglutamic acid, the common pharmacological (USP) form known as folic acid, is not found significantly as such in the body and appears to be absorbed differently than folate (Herbert. 1999). Folic acid is not found in foods, but folate is (23). Herbert reports a study found ‘that consumption of more than 266 mg of synthetic folic acid (PGA) results in absorption of unreduced PGA, which may in fact interfere with folate metabolism for a period of years’ (Herbert. 1999).
  
  Against that backround the fact that the natural food complex folate is absorbed only 1.07 times more into the blood, yet retained 2.13 times more in the liver than isolated USP folic acid (Vinson. 1989) appears less important than the potential interference of excess folic acid intakes with the metabolism of "true" folate which has been shown to trigger liver fibrosis (Marsillach. 2008) and is associated with the development and progression of cancer (with the exception of colorectal cancer | Kim. 2008; Ulrich. 2006).
• Vitamin C, ascorbic acid - The name gives it away, there is no chemical difference between "natural" and "synthetic" vitamin C; it's both plain ascorbic acid. What is missing if you get your vitamin C in pill instead of apple, citrus-fruit and other food-born forms are yet
  the active form of vitamin C, dehydroascorbic acid (DHAA), and its natural synergists which are required for vitamin C to work optimally.
  
  Studies have shown that the "bioavailability of vitamin C in food and 'natural form' supplements is not significantly different from that of pure synthetic AA" (10) which is true, when we look at ascorbic acid in isolation like Mangels et al. (Mangels. 1993) did.
  

  

  Mangels et al. compared the rate (dVit-C/dt), i.e. the slope of the graphs that depict the repletion rates after an 8-week cycle on a vitamin C deficient diet for various forms of vitamin C (Mangels. 1993).

  Mangels et al. did yet ignore the individual and synergistic effects of DHAA or other food constituents associated with natural vitamin C which may have positive effects other than raising serum ascorbate levels. Preliminary data from Vinson et al. (1988) however suggests that vitamin C complexed in food is absorbed 1.74 times more into red blood cells than isolated USP  ascorbic acid, while another found it to be 1.35 times more absorbed into the plasma.
  
  A result that leaves no doubt that simple serum vitamin C measurements as they are done in most studies may be insufficient to identify the subtle advantages of natural vitamin C which does not come in pill form (don't believe the supplement companies claiming they used "natural vitamin C" had figured out what you need to imitate nature).
• Vitamin D - While it has not been proven that any single USP isolated form of vitamin D has all the benefits as natural occurring forms of vitamin D, there is also insufficient evidence that the currently (over-)hyped vitamin D3 supplements alone would be insufficient and should be replaced by something like a "natural full spectrum vitamin D supplement".
  

  

  25OHD content (µg/100g) of chicken & egg, pork, beef, fish, dairy (various sources; more)

  One thing to keep in mind, though, is the fact that there is more to vitamin D than D3; naturally high vitamin D foods like eggs, for example, are "high vitamin D foods" that contain, among other isoforms of vitamin D, also the already active form calcitriol and may thus have a significantly more pronounced health benefit than powders, caps and pills. 
• Vitamin E - As SuppVersity reader you know that supplemental alpha-tocopherol pills have little to do with the full spectrum of tocopherols and trienols foods have to offer.
  
  I have written about this in the past so extensively that I don't want to explain everything for the 10414th time. So, if you are interested in tocotrienols and tocopherols, browse the archive. What I would like to focus on, today, is the difference between synthetic and natural alpha-tocopherol. What is undebated is the that synthetic vitamin E is mixture of eight epimers’, while natural alpha-tocopherol contains only the [d]-epimer of alpha-tocopherol (9). As Thiel points out in his review, the existing evidence clearly

  "indicates that although synthetic vitamins have some of the benefits of natural vitamins, they really do not replace all the benefits of natural ones" (Thiel. 2000).

  This is not surprising, since un foods, natural vitamin E is always found with lipids and other food substances of which Acuff et al. that it is absorbed 3.42 times better than synthetic vitamin E in cord blood during pregnancy.
  
  

  

  The higher urinary excretion of synthetic (d₆) vs. natural (d₃) vitamin E suggests that the human body wants to get rid of the synthetic mix (Traber. 1998).

  Similar results have been observed in rodents, where vitamin E complexed in foods was 2.6 times more retained than isolated USP d-alpha tocopheryl acid succinate (which is the so-called ‘natural form’ once it is isolated from its food complex | Venson. 1989). Results that are in line with observations, Traber et al. made, when they studied human urine and fount that natural vitamin E was not only 2.7 times better absorbed than synthetic vitamin E, but that the body may want to rid itself of the synthetic as quickly as possible (Traber. 1998). 

Bottom line: If you briefly recap the previously reported results, it appears as if the divide between natural and synthetic was less pronounced than some bullocks-website would have it. On the other hand, the often-heard claim that natural and synthetic vitamins were identical is questionable and in some cases like folic acid, vitamin E and others simply false.

One of the reasons we even have to worry about adequate vitamin intakes despite living in abundance, is the quality of our foods (or rather their lack of quality). Food processing techniques can reduce the amount of every known essential vitamin. The refining of rice reduce B-complex vitamins and initially led to deaths in Asia due to beriberi. And even if synthetic USP vitamins are added to white rice, it does not contain the same nutrients as unpolished brown rice (nor does white
flour contain the same nutrients as whole flour).

The reductions in liver vitamin A + E in pigs fed diets containing the fat substitute Olestra and identical amounts of synthetic vits what happens when we replace natural vitamin (Daher. 1997).

"The refining of whole grains (including wheat, rice, and corn) has resulted in a dramatic reduction of their natural food complex nutrients. The milling of wheat to white flour reduces the natural food complex vitamin and mineral content by 40–60%. Various food processing techniques (including pasteurization of milk) reduce the available vitamin B6 in foods by 10–50%. The recently introduced artificial fat olestra (also known as Olean) robs the body of oil soluble vitamins (vitamins A, D, E, and K) and carotenoid antioxidants (betacarotene, lutein, lycopene) [...] Irradiation of meat and other foods ‘changes the characteristics of food’ and has been found to reduce levels of vitamins A, B1, B6, E, K, and other nutrient levels" (Thiel. 2000).

The list could and will be continued, after all it appears to be certain that hitherto unknown nutrients will also be affected from food processing; and even if we found all of them and replaced them with USP isolates it is, we cannot be sure that the effects would be better than for some of the previously discussed vital nutrients. Against that background you don't have to be "paleo" to ask yourself if the synthetically enhanced foods will ever offer all, or even almost all of the health benefits the original unprocessed foods have | Comment on Facebook!

References:

• Acuff, Robert V., et al. "Transport of deuterium-labeled tocopherols during pregnancy." The American journal of clinical nutrition 67.3 (1998): 459-464.
• Daher, George C., Dale A. Cooper, and John C. Peters. "Physical or temporal separation of olestra and vitamins A, E and D intake decreases the effect of olestra on the status of the vitamins in the pig." The Journal of nutrition 127.8 (1997): 1566S-1572S.
• Ensminger A. H., Ensminger M. E., Konlade J. E., Robson J. R. K. Food & Nutrition Encyclopedia, 2nd ed. New York: CRC Press, 1993.
• Fallon, Michael B., And James L. Boyer. "Hepatic toxicity of vitamin A and synthetic retinoids." Journal of gastroenterology and hepatology 5.3 (1990): 334-342.
• Herbert, Victor, and K. C. Das. "Folic acid and vitamin B12." Modern nutrition in health and disease 1 (1994): 402-25.
• Herbert V. Folic Acid In Modern Nutrition in Health and Disease, 9th ed. Baltimore: William & Wilkins, 1999: 433–446.
• Hui J. H. Encyclopedia of Food Science and Technology. New York: John Wiley, 1992.
• Jenkins, D. J. A., T. M. S. Wolever, and A. L. Jenkins. "Diet factors affecting nutrient absorption and metabolism." Modern nutrition in health and disease 8 (1994): 583-602.
• Kanno, Choemon, et al. "Binding form of vitamin B2 in bovine milk: Its concentration, distribution and binding linkage." Journal of nutritional science and vitaminology 37.1 (1991): 15-27.
• Kim, Young-In. "Folic acid supplementation and cancer risk: point." Cancer Epidemiology Biomarkers & Prevention 17.9 (2008): 2220-2225.
• Macrae R., Robson R. K., Sadler M. J. Encyclopedia of Food Science and Nutrition. New York: Academic Press, 1993. 
• Mangels, Ann R., et al. "The bioavailability to humans of ascorbic acid from oranges, orange juice and cooked broccoli is similar to that of synthetic ascorbic acid." The Journal of nutrition 123.6 (1993): 1054-1061.
• Marsillach, Judit, et al. "Moderately high folic acid supplementation exacerbates experimentally induced liver fibrosis in rats." Experimental Biology and Medicine 233.1 (2008): 38-47.
• Ross A. C. Vitamin A and retinoids. In Modern Nutrition in Health and Disease, 9th ed. Baltimore: William & Wilkins, 1999: 305–327.
• Rothman, Kenneth J., et al. "Teratogenicity of high vitamin A intake." New England Journal of Medicine 333.21 (1995): 1369-1373.
• Schelling, Gerald T., et al. "Bioavailability and interaction of vitamin A and vitamin E in ruminants." The Journal of nutrition 125.6 Suppl (1995): 1799S-1803S.
• Schumann, K, et al.  "Bioavailability of oral vitamins, minerals, and trace minerals in perspective". Arzneimittelforschung, 47 (1997), pp. 369–38.
• Tanphaichitr V. Thiamin. In Modern Nutrition in Health and Disease, 8th ed. Philadelphia: Lea & Febiger, 1994: 359–365.
• Thiel, R. "Vitamins are naturally found in food complexes." ANMA Monito 3.1 (1999): 5-9.
• Traber, Maret G., Angelika Elsner, and Regina Brigelius-Flohé. "Synthetic as compared with natural vitamin E is preferentially excreted as α-CEHC in human urine: studies using deuterated α-tocopheryl acetates." FEBS letters 437.1 (1998): 145-148.
• Ulrich, Cornelia M., and John D. Potter. "Folate supplementation: too much of a good thing?." Cancer Epidemiology Biomarkers & Prevention 15.2 (2006): 189-193.
• Vinson, Joe A., and Pratima Bose. "Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract." The American journal of clinical nutrition 48.3 (1988): 601-604.
• Vinson J., Bose P., Lemoine L., Hsiao K. H. "Bioavailability studies". In Nutrient Availability: Chemical and Biological Aspects. Cambridge (UK): Royal Society of Chemistry, 1989: 125–127.
• Vinson, Joe A., et al. "A citrus extract plus ascorbic acid decreases lipids, lipid peroxides, lipoprotein oxidative susceptibility, and atherosclerosis in hypercholesterolemic hamsters." Journal of Agricultural and Food Chemistry 46.4 (1998): 1453-1459.

Vitamins B1, B2, B5 & B6 & Glucose Management | Part VII of the "There is More To Glucose Control Than Low Carb"- Series. Any Real Benefit From Supplementing With "Bs"

Funny or obscene? A woman w/ low vitamin B and thus fortified cornflakes is among the "top images" Google will show you, when you search for B-vits

There is an often overlooked reason I am addressing thiamin (B1), riboflavin (B2), panthotenic acid (B5) and pyridoxine (B6) in one installment of the "There is More to Glucose Control Than Carbohydrates"-Series (read previous installments): They are all necessary to store glycogen in the liver (Supplee. 1942).

In general, a whole foods diet, as recommended in previous SuppVersity articles will easily cover the B-vitamin needs of the average sedentary and physically active individual - in spite of minimally increased requirements for B2 & B6, in particular (Manore. 2000; Woolf. 2008).

You can learn more about this topic at the SuppVersity

Proteins, Peptides & Blood Glucose

SFA, MUFA, PUFA & Blood Glucose

Vitamin D & Diabetes

Glucose Manager Calcium?

Flush & No-Flush Niacin & Diabesity

Vitamin C & Glucose Control

As a SuppVersity reader you do yet know that "adequate" and optimal intakes can differ significantly and the fact that the provision of additional B-vitamins does not have ergogenic effects does not exclude the possibility that it may have beneficial effects on blood glucose management.

The initially mentioned inability to convert glucose to glycogen and to store the latter in the liver, for example, would already set you up to increases in blood glucose levels. The latter will in turn increase the urinary loos of the water-soluble vitamins, so that a deficiency in one of the initially named B-vitamins could trigger a whole "pro-diabetic" cascade that leaves the by then (pre-)diabetic individual deficient even in those of the B-vitamins of which he or she is actually getting enough from his or her diet (+ supplements).

Annual spending Alzheimer patients >65y in the US from 2010 to 2050 (projection, in billion U.S. dollars;  Alzheimer's Association. 2010)

This article is exclusively about the beneficial effects of b-vitamins on glucose control: The conclusions I draw based on the evidence presented in this article do not affect potential cognitive benefits from "optimal" (=within the RDA) intakes of B-vitamins (in particularly folate, and B-12, which are not part of this overview, anyway) in the young (Herbison. 2012) and old , where they are furthermore "confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline" (Douaud. 2013).

Conclusive evidence for anti-diabetic or insulin-sensitizing effects of B-vitamin supplements is yet still scarce. Even the notion that (pre-)diabetics suffer from low levels of the said B-vitamins is still controversial. This does not mean, though, that there were no promising study results I could report. For thiamine, for example, ...

• 

  Figure 1: Effects of lipophilic thiamine on HbA1c (top) and insulin requirements (bottom) of type I diabetics (Valerio. 1999(

  Valerio et al. report that the provision of a lipophilic form of thiamine (benzoyloxymethyl-thiamin) at 50mg/day lead to improvements in HbA1c and reduced insulin requirements in children with type I diabetes (Valerio. 1999) - the difference between the active and the placebo arm of the study did yet not reach statistical significance
• Obrenovich et al. report in a 2003 that thiamine, or rather benfothiamine bocks the oxidative damage due to the presence of excessive amounts of glucose in the blood of a rodent model of diabetes - their results have been replicated in human studies by Stirban et al. an other researchers several times over the past decade (Stirban. 2006)

Corresponding evidence for riboflavin is hard to find. While there are studies that suggest the presence of reduced levels of this b-vitamin in both type I and type II diabetics, direct beneficial effects of vitamin B2 supplementation on glucose management have not been reported.

A very similar picture, i.e. reduced levels in type II diabetics, but no reports of direct metabolic benefits from the provision of supplemental vitamin B5 from randomized controlled human trials, emerges if you do a database search for panthotenic acid.

Figure 1: 2h glucose and insulin response to oral glucose tolerance test before (white) and after 25 days of B5 depletion (red), as well as during B5 refeed (violet) in a healthy male subjects (Bean. 1995)

The results of a study from the mid 1950s, when scientists still put healthy individuals on nutritionally deficient diets still indicate. After 25 days without significant amounts of panthotenic acid in the diet, the subjects' insulin sensitivity was notably compromised (Figure 1, red) and was not normalized within only 10 days on a diet with 133x the normal amount of panthotenic acid (Figure 1, violet).

Mind the vitamin <> vitamin interactions: Even if there is no reason for high dose pantothenic acid supplementation to inhibit the cellular uptake of glucose directly, it's well possible that it messes with glucose metabolism via interactions with other water solube vitamins like vitamin B6 aka pyridoxin, the excretion of which is increasing, whenever the intake of panthothenic acid exceeds an (in humans undetermined) sane threshold.

In fact, the extreme elevation of the insulin levels in the "reload phase" would rather suggest that extreme amount of vitamin B5 will compromise, not improve your insulin sensitivity - contrary to edema, severe fatigue, joint pains, reduced protein metabolism, reduced phosphorus, raised VLDL triglycerides, calcification (from calcium pantothenate), dehydration, gastrointestinal symptoms, and depression, a decreased insulin sensitivity is yet not on the "official list of side effects"* of high panthotenic acid intakes (*by "official" I refer to the lists everyone copies ad pastes from the major health information outlets on the Internet).

And what about B6? It's in all my supplements, so it must be good!

If I had to write the bottom line to today's installment of the "There is More to Glucose Control Than Carbohydrates" series now, it would probably be very short and certainly very disappointing for the various supplement junkies out there. Luckily (?) there is still one of the B-vitamins missing: Pyridoxine or vitamin B6 - and you should expect the only B-vitamin that can produce severe toxic effects when it is consumed in very high amounts chronically (peripheral nerve damage) should be able to bring about at least minimal increases in insulin sensitivity / cellular glucose uptake, as well, right?

Well, unfortunately, that's not the case. In 1980, already, a group of scientists from the Gandhi Medical College Hospital in India were able to show that the provision of 40mg of pyrodixine per day had "did not bring about any significant alterations in either the oral glucose tolerance or the insulin response to glucose" in thirteen adult maturity-onset diabetics - and that in spite of the fact that 7 of them were actually vitamin B6 deficient!

Mind the "hidden" B-sources: If you are still concerned that you may not be getting your Bs in, you are probably an OTC supplement junkie. In that case I suggest you briefly take a look at the pre-workout, post- workout and whatever other products in your stack... what? Oh, they all contain 10x the RDA and more of these B-vitamins - that's surprising, right?

A major disappointment? Although this article focused exclusively on the benefits of the water-soluble B-vitamins on glucose control, the results are still paradigmatic for the overall "potency" of vitamin-B-supplements. They are all the rage, but the benefits are overblown, in many cases simply non-existent.

If we discard the well established beneficial effects of benfothiamine on the side-effects of elevated blood glucose levels, and the highly disputed benefits of pyridoxine in diabetic peripheral neuropathies (alleviation of sympthoms, no change in nerve damage; Bernstein. 1988 & 1990), there is actually no reason to even consider taking extra amounts of any or all of these vitamins if you are (a) no diabetic and (b) no junk food eater - and let's be honest, if either (a) or (b) applies you have got more important issues to deal with than potentially suboptimal B-vitamin intakes and their effects on glucose tolerance.

Reference:

• Bean, William B., et al. "Pantothenic acid deficiency induced in human subjects." Journal of Clinical Investigation 34.7 Pt 1 (1955): 1073. 
• Bernstein, A. L., and C. S. Lobitz. "A clinical and electrophysiologic study of the treatment of painful diabetic neuropathies with pyridoxine." Current topics in nutrition and disease (USA) (1988).
• Bernstein, Allan L. "Vitamin B6 in clinical neurology." Annals of the New York Academy of Sciences 585.1 (1990): 250-260.
• Herbison, Carly E., et al. "Low intake of B-vitamins is associated with poor adolescent mental health and behaviour." Preventive medicine 55.6 (2012): 634-638.
• Manore, Melinda M. "Effect of physical activity on thiamine, riboflavin, and vitamin B-6 requirements." The American journal of clinical nutrition 72.2 (2000): 598s-606s.
• Supplee, G. C., R. C. Bender, and Z. M. Hanford. "Interrelated vitamin requirements. The influence of thiamin, riboflavin, pantothenic acid and vitamin B6 on liver glycogen reserves." Journal of the American Pharmaceutical Association 31.7 (1942): 194-198.
• Valerio, G., et al. "Lipophilic thiamine treatment in long-standing insulin-dependent diabetes mellitus." Acta diabetologica 36.1-2 (1999): 73-76.

SuppVersity Science Round Up Seconds: Wheat Gluten Hydrolysates Fail, Exposure to Air Pollutants During Workout Reduces Brain Benefits, Homocysteine, B-Vitamins, Cognitive Impairment and Mortality

Before the profound weight loss (A) you don't see any of the glucose sucking and fad burning brown fat depots (black spots in B) on the neck of the in (B) 'foermerly obese', now only 'overweight' subject (also take a look at how the visceral fat in the abdominal region in (A) is actually pushing the organs upwards; img Vijgen. 2012)

Those of you who have listened to yesterday's show will have noticed that despite its flow the number of things you can discuss in a 1h podcast is simply very limited, to say the least. This is also why these Friday posts are probably never going to be simple summaries of the SuppVersity Science Round Up of the day before. The same is true for today and still I decided not to use the allegedly lame logo I did for the first two installments, but provide you with some 'real science' evidence of the absence of brown adipose tissue on the obese and it's magical reappearance after shedding 100lbs+ subsequent to a gastric bypass operation, instead (see image on the right).

Assuming that you have no idea what this "evidence" is for, I would suspect that you missed the live show yesterday and also did not find the time to download and listen to the podcast, yet -- right? Well, you should either download and listen to the show now and digest the Seconds later, or you read the following paragraphs first and download the podcast later.

What is not an option, however, is to miss one or another - I mean you can hardly want to eat the seconds if you have not had the main dish yet... and after listening to the podcast, I cannot imagine you don't want at least some seconds. Apropos seconds, here are today's seconds...

• Wheat gluten hydrolysate is not the new goto protein supplement - certainly not for female distance runners and probably not for anyone else, either! These are the kinds of studies that really annoy me. Studies that start out with blatant statements like "WGH [Wheat gluten hydrolysate] has been reported to suppress post-exercise rises in serum creatine kinase in male distance runners" (Hirao. 2012).
  
  

  

  Figure 1: CK, AST, ALT response in the "success trial" with men. In women even the miniscule beneficial effect on CK was not there. No reason to even think about buying a gluten hydrolysate as you new go-to protein supplement with only 5.6g of leucine/100g (whey has 50% more) and almost no GSH replenishing cysteine in it (0.9g vs. 3g+ in whey, which is more than +200% more).

  Sentences like that make the null-results of the study they precede look like the exception to the rule and are still nothing but a concession to a bias (let's hope not due to the grant from Nisshin Pharma Inc. which was the manufacturer of the wheat gluten hydrolysate used in this study). A bias, due to which an isolated observation as the slightly blunted increase in CK is blown up as if a slightly lower CK level was what could turn a sedentary pencil pusher into the next Hussein Bolt (Aoki. 2012).
  
  So, even if you are not afraid of the evil in gluten (which I believe not everyone has to), I strongly caution against making the switch from a high EAA protein with ton's of GSH boosting cysteine in it like whey to a mediocre grain protein, which is a potential allergen and contains tons of glutamine your body will readily turn into glucose, once it passes through the portal veign into the liver (I bet a large part won't even make it into systemic circulation).
  
  And as far as the purported "gender difference" goes the study at hand tries to blame the null result on (Hiriao. 2012), I suspect that it is rather the indisputable difference between the long-distance running at a continuous pace the women in the study at hand did, versus the totally different strains the guys in the previous study were exposed to during a soccer training + mini-match, which made the difference.
• Working out next to a street takes away some of the beneficial cognitive effects due to ultrafine particulate matter (UFPM) exposure. "Working out in the fresh air will promote weight loss more than working out inside." You heard me state that in one of the previous installments of the SuppVersity Science Round Up on Super Human Radio. Now this is still correct and based on sientific evidence, but at least as far as the cognitive benefits are concerned, working out outside does also have its downsides - at least for those of you who live in the inner city area.
  
  

  

  You better watch what you breath while you run.

  During a 12-week program the researchers from the Universiteit Brussel, the Hasselt University and the Royal Military Academy measured the improvements in physical performance, changes in serum markers and corresponding ultrafine particulate matter (UFPM) concentrations in the enviromnent in which their 15 previously untrained subjects conducted their aerobic training program thrice a week (Bos. 2012). What Bos et al. found was that the UFPM levels were signfificantly higher in the urban compared to the rural environment and that the higher UFPM exposures correlated with increases in leukocyte counts (p = 0.02), neutrophil counts (p = 0.04), and eNO levels (p = 0.002) that were exclusively observed in the group that trained in the urban environment.
  
  With the latter being markers of inflammation which exert their effects systemically, i.e. not just in the lung or musculature of which you may be thinking now, but also in the brain, it is no wonder that
  

  "reaction times on the Stroop task improved in the rural group (p = 0.001), but not in the urban group" (Bos. 2012). 

  What's comforting, though, is that the physical fitness did increase to a similar extend in both arms of the study.
• Homocysteine levels, mortality, cognitive impairment and which nutrients can offer some protection. I am not sure about what your impression is, but for whatever reason homocystein seems to be 'out of vogue' -- probably no room for it on the research agenda with all the hype surrounding vitamin D. It used to be all the rage in CVD risk research and today's news item is actually ain't about cardiovascular health, either.
  
  What the researchers from China and Taiwan actually were interested in was the correlation of high and low homocysteine levels with cognitive impairment and the corresponding nutrient intakes. In that Xiu et al. paid particular attention to the "B-vitamins" and found the following correlations between the mortality, cognitive status, homocystein levels and nutrient intake of their 1412 study participants (Xiu. 2012):
  

  • 

    Figure 2: Unadjusted mortality in the four quartiles of homocysteine levels (top); mortality according to homocysteine levels in subjects with different degrees of cognitive impairment (based on Xiu. 2012)

    if you go by the unadjusted data in figure 2, it's plain obvious that the all-cause mortality increases linearly from one quartile to the other 
  • this relation between plasma homocysteine levels and all mortality remained statistically significant after adjustments for age, sex, smoking status, BMI, physical function and general health were made
  • of the general foods, the scientists assessed, only regular fish intake had a statistically significant effect on homocysteine levels, with higher intakes being associated with lower homocysteine levels
  • of the b-vitamins choline was the only one with a significant association with plasma homocysteine levels (suggested read "Old School Supplement Choline Could Save Your Live and Liver!") 
  • neither betaine, nor vitamin B1, B2, B3 or B6 intakes did show statistically significant correlations with plasma homocysteine (not even "borderline significant; p > 0.15 for all, most way hither)
  • of the plasma markers, folate showed a highly significant correlation with homocysteine (14.4 nmol/L in the lowest HCY and 8.70 nnmol/L in the highest HCY group)
  • PLP, the active form of vitamin B6, came in close second with 70.3 nmol/l in the lowest HCY quantile and only 44.4 nmol / l in the highest quantile.
  Now, if you consider the fact that higher intakes of B-vitamins are probably not doing much to lower homocysteine levels int he elderly (at least not dose-dependently, when they are already getting enough) oddity #1, another look at the data in figure 2 will reveal oddity #2: The surprisingly high mortality in the lowest homocysteine quartiles in the patients with severe cognitive decline - how come? I mean, with low homocysteine they should not be at risk of having severe cognitive decline, anyway - right?
  
  Actually if you follow this rationale you can almost answer the question yourself. If you have low homocysteine and severe cognitive decline, the severe cognitive decline can hardly be from high homocysteine levels, so it must have another obviously pathological reason, or as the scientists have it
  

  "The joint effects of the 2 variables [homocysteine and cognitive decline] were most pronounced with severe cognitive impairment where mortality HRs ranged from 5- to 18-fold across a wide range of homocysteine concentrations. The findings with hypohomocysteinemia provide some insight into what might be an optimal range for this analyte in peripheral blood and tissues. The low concentrations may be seen with severe illness and malnutrition, and our study population comprises the health-vulnerable aged. For these reasons, we adjusted these associations for BMI (using the World Health Organization chronic energy deficiency category of, 18.5 kg/m 2 ), and we excluded those who died in the first year of follow-up. The findings were unchanged. Because mortality among the very old may have skewed the joint effects, these are presented for those ≤75 years and over, but again with similar findings." (

  A sarcastic person would now probably say: "We all have to go some time!" and just wave his hands at these results. True! And I am the last to advice you to become over-anxious. Yet in the mean time it would appear prudent to make sure to get your homocysteine levels checked from time to time, not to forget that choline is a b-vitamin as well and not to fall for the idea that you cannot overdose on B-vitamins - I don't have to remind you of the negative effects, specifically folic acid supplementation can have on all sorts of cancer (e.g. breast cancer, where a high folic acid intake from foods and supplements is associated with a +30% risk of cancerous growth; cf. Kim. 2006).

In case you are looking for the post on "ammonia accumulation brain-fog, toxicity, liver 'pathologies' and workout performance", yeah it was on the list, but I decided it would be a shame to tackle that within a short two paragraph seconds items. Don't worry I am not going to forget about it, after all its in my humble opinion one of the main reasons the diets and workout regimen of the many ambitious physical culturists fail. If you are still looking for more and have not listened to the podcast, yet, this would be the right moment to download the file from the Super Human Radio Network server (click here to download), otherwise the latest short news on the SuppVersity Facebook Wall may offer some diversion ;-)

References:

• Aoki K, Kohmura Y, Suzuki Y, Koikawa N, Yoshimura M, Aoba Y, Fukushi N, Sakuraba K, Nagaoka I, Sawaki K. Post-training consumption of wheat gluten hydrolysate suppresses the delayed onset of muscle injury in soccer players. Exp Ther Med. 2012 Jun;3(6):969-972. Epub 2012 Apr 3.
• Bos I, De Boever P, Vanparijs J, Pattyn N, Panis LI, Meeusen R. Subclinical Effects of Aerobic Training in Urban Environment. Med Sci Sports Exerc. 2012 Oct 15.
• Cankurtaran M, Yesil Y, Kuyumcu ME, Oztürk ZA, Yavuz BB, Halil M, Ulger Z, Cankurtaran ES, Arıoğul S. Altered Levels of Homocysteine and Serum Natural Antioxidants Links Oxidative Damage to Alzheimer's Disease. J Alzheimers Dis. 2012 Oct 29.
• Guest PC, Urday S, Ma D, Stelzhammer V, Harris LW, Amess B, Pietsch S, Oheim C, Ozanne SE, Bahn S. Proteomic analysis of the maternal protein restriction rat model for schizophrenia: Identification of translational changes in hormonal signalling pathways and glutamate neurotransmission. Proteomics. 2012 Oct 16.
• Hirao T, Koikawa N, Aoki K, Sakuraba K, Shimmura Y, Suzuki Y, Sawaki K. Female distance runners show a different response to post-workout consumption of wheat gluten hydrolysate compared to their male counterparts. Exp Ther Med. 2012 Apr;3(4):641-644.
• Kim YI. Does a high folate intake increase the risk of breast cancer? Nutr Rev. 2006 Oct;64(10 Pt 1):468-75.
• Vijgen GH, Bouvy ND, Teule GJ, Brans B, Hoeks J, Schrauwen P, van Marken Lichtenbelt WD. Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2012 Jul;97(7):E1229-33. Epub 2012 Apr 24.
• Xiu LL, Lee MS, Wahlqvist ML, Chia-Yu Chen R, Huang YC, Chen KJ, Li D. Low and high homocysteine are associated with mortality independent of B group vitamins but interactive with cognitive status in a free-living elderly cohort. Nutr Res. 2012. Ahead of print.

B-Vitamins & Diabetes: Protective or Causative?

In a very interesting study, scientists from China and Japan (Zhou. 2010) found that "long-term exposure to high level of the B vitamins may be involved in the increased prevalence of obesity and diabetes in the US in the past 50 years". At first this appears to be counterintuitive, since we have been told over and over that B-Vitamins are not only good for our health, but that we could not even "overdose" them. While the latter has been questioned for years and certainly is not the case for e.g. B6 and niacin, even the former seems questionable, if you read the results from the above mentioned study:

The prevalences of diabetes and adult obesity were highly correlated with per capita consumption of niacin, thiamin and riboflavin with a 26- and 10-year lag, respectively (R2 = 0.952, 0.917 and 0.83 for diabetes, respectively, and R2  = 0.964, 0.975 and 0.935 for obesity, respectively). [...] The relationships between the diabetes or obesity prevalence and per capita niacin consumption were´similar both in different age groups and in male and female populations. The prevalence of adult obesity and diabetes was highly correlated with the grain contribution to niacin (R2 = 0.925 and  0.901, respectively), with a 10- and 26-year lag, respectively.

These results (especially those referring to the detrimental effect of niacin) confirm test-tube studies conducted by a group of scientists from South Korea earlier this year (Choi. 2010), who found that

NA [nicotinic acid] alters gene expression in insulin-sensitive tissues by various mechanisms. Some of the NA-induced changes in gene expression are discussed as potential mechanisms underlying wanted and unwanted effects of NA treatment.

Just anecdotal: My personal perspective on B-vitamins has changed since my overall energy and well being, as well as my physique have largely improved after stopping to take those B-vitamin (over-)loaden mulit-vitamin preparations like Now ADAM, CL Orange Triad, Animal Pak, ON Opti-Men etc. But remember: it is mere speculation that this could in fact be related to their high B-vitamin contents - could be any other constituent, as well.

Eat Rice, Stay Healthy!?

A recently published study (Fulgoni. 2010) analyzing data from 25 374 eligible participants identified as rice consumers study on the correlation of rice-eating to several markers of metabolic health showed that people who ate at least one serving of rice (white or brown) a day tend to have

better health and diet parameters including less total fat, saturated fat, and added sugars; higher amounts of more than 12 essential vitamins and minerals, including iron, folate, and other B vitamins; more fruit and legumes; nearly 4 tsp (16 g) less added sugar; and 7 g less solid fats. For the 19- to 50-year-old subgroup, main results (P < .05) also showed rice consumption associated with reduced likelihood of being overweight or obese, 34% reduced risk of high blood pressure, 27% reduced likelihood of having an increased waist circumference, and 21% reduced risk of metabolic syndrome.

This, however, should not encourage you to just add one serving of rice to your bad diet habits, because the most important information coming from the study is the first one: Rice eaters tend to have better diet parameters. In other words their general dietary regimen is more healthy, no wonder they have a reduced likelihood of obesity and health issues. Overall, rice is still a very dense source of energy and overeating on it would not be advisable, both from a caloric, as well as (this is more important) from a nutritious point of view - with its high amount of carbohydrate one serving of rice may well amount to all the carbs you may eat, if you follow a heart healthy low carbohydrate diet. Bottom line: Moderation is the key!

Prepare for the Winter: Get your Supply of Vitamin D Supplements

Figure 1: In Great Britain Vitamin D3
supplementation appears indicated
at least in the winter month

A recent study by researchers (Webb. 2010) from the School of Earth Atmospheric and Environmental Sciences at the University of Manchester highlight the importance of maintaining "late-summer 25-OH(D3) levels" throughout the winter month. In their investigation among 125 white Caucasians aged 20-60 years in Greater Manchester they found:

Dietary vitamin D remained low in all seasons (median 3.27 mug/day, range 2.76-4.15) while personal UV exposure levels were high in spring and summer, low in autumn and negligible in winter. Mean 25(OH)D levels were maximal in September (28.4 ng/mL; 28% optimal, zero deficient (< 5 ng/mL)), and minimal in February (18.3 ng/mL; 7% optimal, 5% deficient). A February 25(OH)D level of 20ng/mL was achieved following an average late summer level of 30.4 (25.6 to 35.2) and 34.9 (27.9 to 41.9) ng/mL in women and men, respectively, with 62% variance explained by gender and September levels.

With 50ng/ml 25(OH)D being what is currently considered an optimal vitamin D status by many, additional vitamin D supplementation would thus be warranted even in the summer month. This holds true in view of the results from another recent study (Michaëlsson. 2010) reporting higher all-cause / cancer mortality for very low (<46 nmol/L) or very high (>98 nmol/L) levels of 25(OH)D in a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194) in Upsala.

Going Vegan? Better Get Some B-12 Lozenges

While my personal credo is: "Man is made for eating meat." I respect everyone who - for ethical or whatever reasons - refuses to do so. In spite of that, a recent study by Gilsing et.al. (Gilsing. 2010) found that vegetarians and vegans even more so, have a high risk of being vitamin B12 deficient. In their conclusion on the evaluation of the EPIC-Oxford cohort study, the scientists write:

the results from this study show that vegetarians and vegans have much lower concentrations of
serum vitamin B12 but higher concentrations of folate in comparison with omnivores. Mean serum vitamin B12 was not associated with the duration of adherence to a vegetarian
or vegan diet, which may indicate that mechanisms that maintain circulating concentrations of vitamin B12 are upregulated in vegetarians and vegans. Further research into the health effects of vitamin B12 deficiency and depletion in vegans and vegetarians is warranted , and vegetarians and vegans should ensure a regular intake of sufficient vitamin B12 from fortified foods and/or supplements. (Gilsing. 2010)

Especially if you are an athlete or gymrat, this is another reason to include either a reliable high dosed B-vitamin complex or another source of  source of additional B12 in your supplement. In case you are already taking a multi covering all your needs, don't bother taking additional B-vitamins - although it is often stated otherwise some of them can produce negative side effects not only in susceptible individuals.