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"No sun, no diabesity protection." The evidence is equivocal and the number of studies low, but there is evidence that this statement could be true.

Ok, its November and not exactly sunny in the Northern hemisphere, but if you look back at the months June-August, how much sun exposure did you actually get, this year? Hardly any? Well, thats bad news, because a recent review of the scant scientific evidence suggests that there is "a role of recreational sun exposure in reducing odds of T2DM incidence" (Shore-Lorenti. 2014).

In view of the fact that the contemporarily available evidence is not exactly comprehensive, you should yet consider the following overview of the potential effects and mechanism as a "work in progress".
As Shore-Lorenti et al. point out, the recent International Diabetes Federation (IDF) Diabetes Atlas (6th edition) describes a snapshot of the global diabetes burden in 2013 and projects this forward to the year 2035.1 Cur rently, an estimated 382 million global citizens have diabetes, costing around $1437 USD in 2013 for each person affected by the condition. Projections based on current trends predict that 592 million people will be living with diabetes by 2035; one in ten people will be affected, with an inordinate amount of fund ing required globally to treat diabetes and manage diabetic com plications ($627 billion USD in 2035).

And while scientists are feverishly searching for a solution for the diabesity epidemic, the ongoing research into the effectiveness of vitamin D supplementation in diabetes have yielded inconsistent results (Mitri. 2011). Against that background it appears almost negligent that only few scientists have yet taken a closer look at the factors that trigger vitamin D sufficiency or rather the global low vitamin D epidemia.

Lack of sun"low vitamin D" - thats not all!

Figure 1: Australians who use sunscreen chronically have 50% reduced vitamin D levels (Matsuoka. 1988)

A lack of sufficient (unprotected) sun exposure - previous studies have shown that chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin (Figure 1 | Matsuoka. 1988) - is one of the factors of which researchers speculate that it contributes to the development of vitamin D deficiency even in those of us who live in areas with a high annual sun-exposure.

Now, if restoring the 25-OHD (vitamin D) levels to normal does not work the anti-diabetic magic it is supposed to do and our D-levels are low due to insufficient sun-exposure, it appears only logical to assume that a lack sun-exposure and not a lack of vitamin D is one of the factors that contributes to the ever-increasing rates of diabesity - in conjunction with the usual subjects, obviously: The consumption of a junk-food diet and a lack of exercise, which is without doubt the #1 reason people in the Western Obesity Belt develop obesity, diabetes and the other characteristics of the metabolic syndrome.

Against that background its all the more surprising that evidence for an association between sun exposure and fasting serum glucose level is scarce.

"Typically, the lowest glucose levels occur during summer and levels peak in winter or early spring. One of these analyses [Shore-Lorenti et al. reviewed] went beyond simply observing trends in fasting glucose throughout the year: fasting plasma glucose was positively correlated with a measure of available sun and inversely correlated with temperature." (Shore-Lorenti. 2014)

The study, the researchers from the University of Melbourne have in mind was conducted by Suarez, L. & Barrett-Connor, E. in 1988, already.
If you look at the data Suaraez & Barret-Connor generated, you can see - even without their statistical sophisticated analysis - that there is a significant correlation between possible sun exposure (Figure 1, left) and the fasting plasma glucose levels (Figure 1, right).
Since physical activity may follow a similar circannual rhythm, its yet difficult to exclude that the effects Suarez & Barret-Connor observed were not corroborated (or corrupted?) by an increase in physical activity. However, Shore-Lorenti et al. believe that ...

"[...c]onsidering that the unadjusted analyses and three of four of the studies included in the best evidence synthesis (including the study adjusting for physical activity) are in agreement, it is possible that future research may confirm that sun exposure reduces fasting glucose" (Shore-Lorenti. 2014).

Shore-Lorenti et al. also point out that the highest level of evidence (moderate) for an association between sun exposure and T2DM outcomes in adults originates from the study by Lindqvist et al. (2010). In their paper, the researchers from the Karolinska University Hospital report a reduction in odds of developing T2DM given increased recreational (rather than occupational) sun exposure. 

Figure 2: Leisure time sun exposure is associated with a significantly reduced risk (up to 50%!) of developing T2DM in Swedish adults (Lindqvist. 2010)

In subjects with a low BMI the beneficial effect of using the tanning bed and sunbathing is even more pronounced (-60% risk). In the obese, however, it is significantly reduced (-10%) compared to the average reductions you see in Figure 2.

The fact that only leisure time, but not occupational sun exposure was linked to a significant reduced risk of developing type II diabetes may, as Shore-Lorenti et al. point out be due ...

"[...] to the frequency of sun exposure (perhaps leading to tolerance), duration, intensity and site of exposure (sun protective clothing and behaviour differences between the two settings), or perhaps selection biases for such work (for example, fair-skinned people may avoid occupational sun exposure or a less healthy lifestyle may be associated with manual labour)."

Incidentally, a similar disparity between recreational and occupational sun exposure is well described for risk of developing melanoma (Chang. 2009).

A review by Chen et al. (2008) provides low-level evidence for an association between sun exposure and fasting insulin levels; fasting serum insulin was higher in summer than in winter. Overall, the results are yet inconclusive. A fact, Shore-Lorenti et al. ascribe to "the lack of adjustments made by the included study – particularly for BMI" (Shore-Lorenti. 2014)
Overall, we are thus left with the above overview (Table 1) as a conclusion of which the mere number of "unkown"s and "inconsistent"s tell you that we are not yet at the point to draw a water-proof conclusion.
References:

• Chang, Yu-mei, et al. "Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls." International journal of epidemiology (2009): dyp166. 
• Chen, Shui-Hu, et al. "Community-based study on summer-winter difference in insulin resistance in Kin-Chen, Kinmen, Taiwan." Journal of the Chinese Medical Association 71.12 (2008): 619-627.
• Lindqvist, Pelle G., Håkan Olsson, and Mona Landin-Olsson. "Are active sun exposure habits related to lowering risk of type 2 diabetes mellitus in women, a prospective cohort study?." Diabetes research and clinical practice 90.1 (2010): 109-114.
• Mitri, J., M. D. Muraru, and A. G. Pittas. "Vitamin D and type 2 diabetes: a systematic review." European Journal of Clinical Nutrition 65.9 (2011): 1005-1015.
• Nelemans, P. J., et al. "An addition to the controversy on sunlight exposure and melanoma risk: a meta-analytical approach." Journal of clinical epidemiology 48.11 (1995): 1331-1342.
• Shore?Lorenti, Catherine, et al. "Shining the Light on Sunshine: a systematic review of the influence of sun exposure on type 2 diabetes mellitus?related outcomes." Clinical endocrinology (2014).
• Suarez, L., and E. Barrett-Connor. "Seasonal variation in fasting plasma glucose levels in man." Diabetologia 22.4 (1982): 250-253. 

No, the sun does not kill you. If you control your exposure it may extend your life and improve your life-quality significantly.

Its about time to "let there be light" to illuminate the benefits of regular well-timed exposure to sunlight and its short frequency component. Only recently, researchers from the Japanese National Institute of Advanced Industrial Science and Technology (AIST) were able to show that daytime light exposure has significant beneficial effects on cognitive brain activity. Significant enough to have the subjects perform better on an oddball task and to significantly increase cortical activity related to cognitive processes (Okamoto. 2014).

But is that really all, bright light, or more specifically, the regular and well-timed exposure to bright light can do for you?
Certainly not. I mean if its ill-timed, like the evening use of light-emitting eReaders it will negatively affect your sleep, mess up your circadian rhythm and decrease your alertness on the next morning. Similar results, i.e. drowsiness and suppression of energy metabolism the following morning, have been reported by other studies, as well (Kayaba. 2014).

As a SuppVersity reader you do yet know all about those negative effects from the circadian rhythm series, anyway. Reason enough for me, to focus primarily on all the good stuff, the well-timed exposure to bright light can do for you in todays Special of the SuppVersity Short News.

• If you cant let go off your mobile at night, use blue blocker glasses as a countermeasure for alerting effects of evening light-emitting diode screen exposure - According to researchers from the Psychiatric Hospital of the University of Basel, blue blocker glasses (BB) significantly attenuate LED-induced melatonin suppression in the evening and decrease vigilant attention and subjective alertness before bedtime.
  
  Strangely, though, visually scored sleep stages and behavioral measures collected the morning after were not modified. Still, van der Lely et al. conclude: "BB glasses may be useful in adolescents as a countermeasure for alerting effects induced by light exposure through LED screens and therefore potentially impede the negative effects modern lighting imposes on circadian physiology in the evening "(van der Lely. 2014).
• UV-light protects against "brainflammation" in MS model - Scientists from the University of Wisconsin-Madison report in their latest paper that UV light selectively inhibits spinal cord inflammation and demyelination in experimental autoimmune encephalomyelitis.
  
  Previous studies have already shown that UV radiation (UVR) can suppress experimental autoimmune encephalomyelitis (EAE), an animal model of multiple-sclerosis (MS), independent of vitamin D production. The mechanism of this suppression did yet remain to be elucidated, until Wang et al. (2014) observed that UVR (10kJ/m²) does not just inhibit the inflammation and demyelination of the spinal cord, but will also dramatically and significantly reduce spinal cord chemokine CCL5 mRNA and protein levels.
  
  In conjunction with an increased production of intereron-gamma (IFN-?) and IL-10, which are actually used to treat all sorts of autoimmune diseases, artificial and natural UV light can thus actually "prevent the migration of inflammatory cells into the CNS" (Wang. 2014).

• Melatonin conc. after 4 days w/ dim vs. bright light and tryptophan rich vs. poor breakfast (Fukushige. 2014).

  Bright light in the AM and the consumption of a breakfast thats high in tryptophan can help you maintain a healthy circadian rhythm - In case you are asking yourself how you can grasp all the benefits that are associated with having an intact circadian rhythm, you may be intrigued to hear that researchers from the Fukuoka Womens University have been able to show that an increase in tryptophan intake at breakfast combined with daytime light exposure has beneficial effects on melatonin secretion and sleep quality. As you can see in the figure to the left it will significantly elevate the evening melatonin peak, which is critical for an optimal circadian rhythm.
  
  If you are looking to optimize your internal clock bright light (either sunlight or a 10,000 Lux daylight lamp) + tryptophan (seeds, nuts, soy, cheese, chicken, turkey, fish, oats, beans and eggs are the TOP10 sources) are the way to go. If you want an extra "kick" add some coffee to the equation. This will increase the light responsiveness of the circadian pacemaker - well, at least in mice it does (Diepen. 2014).

• Bright lights at work will keep you sane, happy and alert - If you are working in an insufficiently lit office without natural sunlight, you should be prepared to develop physiological, sleep and depressive symptoms.
  
  Assuming you have a window in your office, you will get a significantly more pronounced total and peak exposure to bright light thats going to correlate with 33% reduced levels of the stress hormone cortisol, a more natural rhythm of melatonin and a reduced risk of minor psychiatric disorders and depressive symptoms (MA) in the evening.
  
  Thats at least what the results of a recent study from the UFRGS in Porto Alegre indicates (Harb. 2014). A study the authors of which proudly say that their "study demonstrated that not only may light pollution affect human physiology but also lack of exposure to natural light is related to high levels of cortisol and lower levels of melatonin at night, and these, in turn, are related to depressive symptoms and poor quality of sleep" (Harb. 2014).

• If you want to light up the darkness, when its actually time to sleep do it with green (555nm) or red, not blue light, which suppresses melatonin (Bonmati-Carrion. 2014).

  Staying away from nightly night exposure may also help to keep your arteries clean even in the old age - Studies indicate that even after  adjustment for confounding factors, including age, gender, body mass index, current smoking status, hypertension, diabetes, dyslipidemia, sleep medication, estimated glomerular filtration rate, nocturia, bedtime, duration in bed (scotoperiod), day length (photoperiod), urinary 6-sulfatoxymelatonin excretion and daytime and nighttime physical activity, exposure to light at night is associated with carotid intima-media thickness (Obayashi. 2014).
  
  If you dont want to develop subclinical carotid atherosclerosis, when you are old, it would thus be a good idea to adhere to the basic rules of sleep hygiene: a dark room and/or blindfolds will keep your arteries clean and may thus save your life ;-)
• If you have kidney problems, get out in the sun if you want to survive - Scientists from the University of California Irvine Medical Center were able to show that dialysis patients residing in higher UV index regions have lower all-cause mortality compared to those living in moderate-high UV regions (Shapiro. 2014).
  
  More specifically, the ~60year-old subjects residing in moderate-high UV index regions had a 16% reduced risk of all-cause mortality. Those living in very-high UV index regions had a 1% higher risk reduction (17%). Interestingly, there was a similar inverse association between UV index and mortality was observed across all subgroups, but it was more pronounced among whites vs. non-whites.
• Wear those shades (or bluelight blocker glasses) before any important sport event - Why? Stupid question. If you dabble around with your smartphone "unprotected" the evening before an important sport event for only 30 minutes, this can influence exercise performance under hot conditions during the subsequent early morning (Thompson. 2014).

Sleep disturbance and adaptive immunity. Following a night of sleep loss, or during a period of sleep disturbance, nerve fibers from the sympathetic nervous system (SNS) release the neurotransmitter norepinephrine into primary and secondary lymphoid organs and stimulate the adrenal gland to release stored epinephrine into systemic circulation. Both neuromediators stimulate leukocyte adrenergic receptors (e.g., ADRB2) and activate nuclear factor (NF)-?B-mediated inflammatory programs (Irwin. 2015).

• If your grandparents have Alzheimers install a timer-based light system - This may not just increase their sleep quality, but it will also improve their behavior and mood as indicated by reduced depression scores on the Cornell Scale for Depression in Dementia and agitation scores from the Cohen-Mansfield Agitation Inventory (Figueiro. 2014).
  
  I must warn you, though: The recent field study from the Rensselaer Polytechnic Institute is promising, but the results should be replicated using a larger sample size and perhaps using longer treatment duration.
• If you have to work night shifts consider using 1-5mg melatonin 1h before you go to bed - Why? You have to counter the natural decline in melatonin production that occurs over consecutive days of night work (Dumont. 2014).
  
  In a recent study from the Sacre-Coeur Hospital of Montreal the melatonin production of the healthy volunteers decreased progressively decreased over consecutive days of simulated night work, both during nighttime and over the 24?h. Interestingly, this decrease was larger in women using oral contraceptives and independent of bright light exposure.
• Get out into the sun and cure your back pain - If your back hurts and neither you or your doctor have a clue why, try getting into the sun. A study from the UMIT in Austria shows that only three sessions in front of 5.000?lx lamp improved the depressive symptoms and reduced the pain intensity in CNBP adults with chronic nonspecific back pain (Leichtfried. 2014).

References:

• Bonmati-Carrion, Maria Angeles, et al. "Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure." International Journal of Molecular Sciences 15.12 (2014): 23448-23500.
• Diepen, Hester C., et al. "Caffeine increases light responsiveness of the mouse circadian pacemaker." European Journal of Neuroscience 40.10 (2014): 3504-3511.
• Dumont, Marie, and Jean Paquet. "Progressive decrease of melatonin production over consecutive days of simulated night work." Chronobiology international 0 (2014): 1-8.
• Figueiro, Mariana G., et al. "Tailored lighting intervention improves measures of sleep, depression, and agitation in persons with Alzheimer’s disease and related dementia living in long-term care facilities." Clinical interventions in aging 9 (2014): 1527.
• Fukushige, Haruna, et al. "Effects of tryptophan-rich breakfast and light exposure during the daytime on melatonin secretion at night." breast cancer 4 (2014): 9.
• Harb, Francine, Maria Paz Hidalgo, and Betina Martau. "Lack of exposure to natural light in the workspace is associated with physiological, sleep and depressive symptoms." Chronobiology international 0 (2014): 1-8. 
• Irwin Michael, R. "Why Sleep Is Important for Health: A Psychoneuroimmunology Perspective." Annual Review of Psychology 66 (2015): 143-172.
• Kayaba, Momoko, et al. "The effect of nocturnal blue light exposure from light-emitting diodes on wakefulness and energy metabolism the following morning." Environmental health and preventive medicine 19.5 (2014): 354-361. 
• Leichtfried, Veronika, et al. "Short?Term Effects of Bright Light Therapy in Adults with Chronic Nonspecific Back Pain: A Randomized Controlled Trial." Pain Medicine 15.12 (2014): 2003-2012.
• Obayashi, Kenji, Keigo Saeki, and Norio Kurumatani. "Light exposure at night is associated with subclinical carotid atherosclerosis in the general elderly population: The HEIJO-KYO cohort." Chronobiology international 0 (2014): 1-8.
• Okamoto, Yosuke, and Seiji Nakagawa. "Effects of daytime light exposure on cognitive brain activity as measured by the ERP P300." Physiology & behavior 138 (2015): 313-318.
• Partonen, Timo. "Obesity= physical activity+ dietary intake+ sleep stages+ light exposure." Annals of medicine 46.5 (2014): 245-246.
• Shapiro, Bryan B., et al. "The Relationship Between Ultraviolet Light Exposure and Mortality in Dialysis Patients." American journal of nephrology 40.3 (2014): 224-232. 
• Thompson, A., et al. "The Effects of Evening Bright Light Exposure on Subsequent Morning Exercise Performance." International journal of sports medicine EFirst (2014).
• van der Lely, Stéphanie, et al. "Blue blocker glasses as a countermeasure for alerting effects of evening light-emitting diode screen exposure in male teenagers." Journal of Adolescent Health (2014).
• Virginie, Gabel, et al. "Dawn simulation light impacts on different cognitive domains under sleep restriction." Behavioural Brain Research (2014).
• Wang, et al. "UV light selectively inhibits spinal cord inflammation and demyelination in experimental autoimmune encephalomyelitis." Arch Biochem Biophys. (2014). [Epub ahead of print]
• Zeitzer, Jamie M., et al. "Millisecond Flashes of Light Phase Delay the Human Circadian Clock during Sleep." Journal of biological rhythms (2014): 0748730414546532.

Dont obsess about "optimal" antioxidant contents, just eat your veggies!

Over the past couple of weeks, ... no actually over the past years I have repeatedly written about the concept of (mito-)hormesis and its consequences for the well-established, but not necessarily accurate free radical theory of aging (and for some people everything else). ROS, i.e. reactive oxygen species, have been established as an important signalling molecule that is - among other things - heavily involved in the insulin sensitizing effects of exercise. "Inflammation" makes muscles grow and burns body fat and the "what doesnt kill me makes me strong" principle appears to reign everywhere you look.
That being said, the latest study from the Institute of Health and Environmental Medicine in Tianjin, China, opens another "anti-antioxidant" Box of Pandora. One that puts a huge questionmark behind the implications of hundreds of thousands of scientific studies, when it says in its title, already: "No correlation is found for vegetables between antioxidant capacity and potential benefits in improving antioxidant function in aged rats"

"Skin of Grape Tomatoes Contains Max. Amount of Antioxidants" - You can find this and dozens of other daily updated SuppVersity Science News on www.facebook.com/SuppVersity

This is a title that may in fact change the way we look at study results like those of a recent study by Valdez-Morales, et al. (2014) investigating the "best" = highest antioxidant tomato, the results of which you are about to find among the ~20/day SuppVersity Facebook News @ www.facebook.com/SuppVersity - dont forget to like it, or youll miss out on the latest science news!

If the results of the study can be confirmed by an independent team for vegetables other than lotus root, rape or cucumber and if there is an identical mismatch between the in-vivo anti-oxidant capacity and the potential benefits in improving antioxidant function in (aged) humans.

This would be big and highly consequential news for nutrition experts, scientists and average Joes and Janes like you and me. Why? Well,...

• any ranking of "superfoods" that was based even partly on in vitro data derived with the good old ferric reducing antioxidant power (FRAP) assay would be invalid, ...
• every scientist who has been following up on "promising" data from FRAP assays would have been wasting his time, ...
• and you may have been eating all the wrong foods for years...

... hell no, as long as you ate your veggies over the past years, I wouldnt worry if you may have made a "suboptimal" selection (which would be different based on whatever new criteria you select).

Figure 1: FRAP value, vitamin C and vitamin E content and total amount phenolics in the powdered vegetables that were added to the rodent diets in the study at hand (Ji. 2014)

Honestly, Id hope that you didnt select your foods only based on the orthorexic principle of maximal antioxidant content, anyways. 

Never forget the three principles of veggie eating: Variety, seasonality, colorfulness

Against that background Id recommend you keep eating your lotus roots, if you like them, although, they have a significantly lower beneficial effect on SuperOxide Dismutase (SOD, a group of antioxidant enzymes) than rape and cucumber.

Figure 2: Serum markers of anti-oxidant status / oxidative damage after 6 weeks on the three experimental diets (Ji. 2014)

Moreover, if you look closely at the data in Figure 1+2, you will realize that lotus may suck at SOD and its ability to reduce hemolysis (the destruction of red blood cells), but will have the most profound beneficial effects on the levels of malondealdehyde (MDA), a marker of lipid oxidation, and the amount of plasma carbonyls, which have - just as in cellular regulation, aging, and disease (Levine. 2002). Just like their similarly radical cousins, carbonyls will thus play a dual role so that in the end, their reduction may not be beneficial in each and every case.
Reference: 

• Ji, Linlin, et al. "No correlation is found for vegetables between antioxidant capacity and potential benefits in improving antioxidant function in aged rats." Journal of Clinical Biochemistry and Nutrition 54.3 (2014): 198-203.
• Levine, Rodney L. "Carbonyl modified proteins in cellular regulation, aging, and disease^{2, 3}." Free Radical Biology and Medicine 32.9 (2002): 790-796.
• Valdez-Morales, Maribel, et al. "Phenolic content, and antioxidant and antimutagenic activities in tomato peel and seeds, and tomato by-products." Journal of Agricultural and Food Chemistry (2014). Accepted Manuscript.

Shouldnt it be obvious that the "happy medium" must be the solution, when high protein leads to brittle bones, and low protein to frail muscle? Sure! But where is this "happy medium"?

Some of you may remember my recent Facebook post "High Protein Diet in the Firing Line. Rodent Study Says: Kidneys Are at Risk". It was based on a press release you could read on all the major science-news outlets on the Internet; a press release that will give the average reader the impression that the corresponding study by Aparicio et al. would "prove" that high protein diets will ruin your kidneys and eventually jeopardize your health (read more).

Another paper (Cao. 2014), Jose Antonio, the CEO of the ISSN and the editor of the ISSNs journal posted on Facebook yesterday, didnt get as much media attention, though.

No wonder, the message of this study is after all not in line with one of the fundamental arguments you will hear, whenever you question the allegedly necessary restriction of total protein intake to 0.8g/kg, maximally 1.2g/kg protein per kilogram body weight day in the current nutritional guidelines:

"[...S]hort-term consumption of high-protein diets does not disrupt calcium homeostasis and is not detrimental to skeletal integrity."

Thats not what you will learn at med-school and it is certainly not in line with the hysteria about protein intakes that are 2x or even 3x higher than the 0.8g protein per kilogram body weight we are supposed to consume. Apropos RDA, the subjects in the control group of the said study by Jay J Cao et al. consumed a diet that contained exactly those 0.8g/kg body weight thats supposed to be good for us. The 21 human guinea pigs in the treatment groups, on the other hand, consumed 2x and 3x more than the average dietitian would recommend and they did so for 31 days (Cao. 2014).

Figure 1: Protein intake (in g/day; left), mineral intake (in mg/day; middle)  and calculated renal acid load (in mEq; right) of 49 normal weight, healthy men (n=32) and women (n=7) who consumed normal (0.8g/day), high (1.6g/kg per day) and very high protein (2.4g/kg per day) energy restricted (40%) diets for 4 weeks (Cao 2014)

If you take a look at the PRAL values in Figure 1, you can see that math (not bio- or physiology!) tells us that this reckless practice could compromises the acid-base balance of the healthy, normal-weight subjects, whose energy restricted diets were modeled on the increasingly popular high protein weight loss diets.

Equations vs. experiments | PRAL vs. urinary calclium loss | theory vs. practive

The urinary analysis the scientists conducted does yet speak a very different language. There is, as the scientists emphasize in the discussion of the results no evidence that

Suppversity Suggested Read: "High protein diet = high protein loss" | more

"habitual consumption of dietary protein at levels above the RDA [would] significantly alter urinary calcium excretion, dietary calcium retention, or markers of bone turnover or BMD, despite increased urinary acidity. These results indicate that diets that are 2 or 3 times the RDA for protein are not detrimental to calcium homeostasis when calcium and vitamin D are consumed at recommended intake"

In that I would like to emphasis the importance of adequate calcium (min. 800mg/day) and vitamin D intakes (800-1000IU/day) and the fallacy of the word "habitual". The study at hand did not test the effects of "habitual" high protein consumption. It tested the effects of short-term (28 days) high protein consumption in a low calorie scenario, which is by definition less prone to produce adverse inflammatory and thus potentially pro-osteoporotic side effects (Mundy. 2007).

Not eating enough protein could increase bone loss, when youre dieting

In view of the fact that the evidence I am about to cite, stems from rodent model of postmenopausal bone metabolism, I deliberately used the word could in the headline of this paragraph. And still, the way in which the low protein diet  "negatively impacted bone mass and magnified the detrimental effects of vitD and/or estrogen deficiencies" (Marotte. 2013) in the pertinent study from the Buenos Aires University is particularly disturbing.
The (postmenopausal) women the scientists try to model with their ovariectomized rats (=rats whose ovaries have been removes) are after all one of the many patient groups who are advised to carefully control their protein intake to make sure that the additional acid load will not compromise their bone health even further and that in spite of the fact that there is ample evidence that the current RDA for protein is inadequate to maintain optimal health, particularly when the total energy intake is restricted and especially in populations who are susceptible to bone loss (Kerstetter. 2005; Chernoff. 2004).

Figure 2: We know for quite some time not that low protein diets decrease the absorp- tion of protein (Kerstteter. 2005). Its not certain if this is "just" a homeastatic me- chanism to stabilize the net/acid balance.

In their 2005 study, Kerstetter et al. were in fact able to show that protein intakes that are 2.6x higher than the RDA increase the effective absorption of calcium from the diet (see Figure 2).

This increase stands in contrast to the significant decrease in calcium absorption the researchers observed in the healthy young (age: 26y) women in the low protein arm (0.7g protein per kg body weight) of the study and should remind us that a reduction in protein intake is not going to stop the insidious loss of bone thats caused by the triage of low estrogen, no exercise and a diet that may be low in protein, but high in acid producing grains (Remer. 1995) and devoid of alkaline fruit and vegetables.

I could now go more into details, but I will just leave you with the notion that the "paleo diet" is, despite its high meat content, among the most kidney-, and above all bone-friendly diets we know. In fact, its fruit and vegetables content yield a net alkaline renal load, and will lead to significant improvements in urinary calcium excretion rates (Appelet. 1997; Frassetto. 2013).   

? Note: If you want more about the "Paleo connection" - let me know this (best on Facebook) and what you would be most interested in and I will address that in a future SuppVersity article.

References

• Aparicio, V. A., et al. "High-protein diets and renal status in rats." Nutrición hospitalaria: Organo oficial de la Sociedad española de nutrición parenteral y enteral 28.1 (2013): 232-237.
• Appel, Lawrence J., et al. "A clinical trial of the effects of dietary patterns on blood pressure." New England Journal of Medicine 336.16 (1997): 1117-1124. 
• Cao, Jay J., et al. "Calcium homeostasis and bone metabolic responses to high-protein diets during energy deficit in healthy young adults: a randomized controlled trial." The American journal of clinical nutrition 99.2 (2014): 400-407.
• Chernoff, Ronni. "Protein and older adults." Journal of the American College of Nutrition 23.sup6 (2004): 627S-630S. 
• Frassetto, L. A., et al. "Established dietary estimates of net acid production do not predict measured net acid excretion in patients with Type 2 diabetes on Paleolithic–Hunter–Gatherer-type diets." European journal of clinical nutrition 67.9 (2013): 899-903.
• Kerstetter, Jane E., et al. "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women." Journal of Clinical Endocrinology & Metabolism 90.1 (2005): 26-31.
• Mundy, Gregory R. "Osteoporosis and inflammation." Nutrition reviews 65.s3 (2007): S147-S151.
• Remer, Thomas, and Friedrich Manz. "Potential renal acid load of foods and its influence on urine pH." Journal of the American Dietetic Association 95.7 (1995): 791-797.

There are alternatives and adjuncts to fluoride you just have to know them.

To start off with the most important information not in, but about this article: This is not an anti-fluoride article.  I am not even going to mention the ongoing debate about the usefulness and safety of fluoride in toothpaste and co.

What I am offering is a concise list of natural agents with similar anti-bacterial properties as fluoride anyone of you can use to improve his tooth hygiene - this includes those of you who believe the whole fluoride scare is another overweight child of the hype generating online health community.

Various anti plaque agents, and other agents like enzymes have been effectively used as prevention of
dental caries. Ever since 1970‘s researchers started to search for non-fluoride agents for the  prevention of dental caries. And as Agarwal write in a recent article in Oral Hygiene & Health, "fluoride agents may serve as adjunctive therapeutics for preventing, arresting or even reversing dental caries" (my emphasis in Agarwal. 2014).

Against that background, the items in the following list should be understood as suggestions; agents I suggest you may want to try to improve your dental health, irrespective of whether you combine them with a fluoride containing toothpaste or not:

• Essential oils: Essential oils have been used for centuries. Only, recently however, has this practice caught scientific attention and scientists began to study the antimicrobial activity against caries-related bacteria.
  
  

  Thyme with its main active ingredient thymol is one of the essential oils you could use in an anti-bacterial mouth wash.

  Essential oils derived from plants are typically a complex mixture of approximately 20-60 compounds that are in solution at various concentrations. Overall, the main chemical group is primarily composed of terpenoids, followed by aromatic and aliphatic constituents. Thymol and eugenol are two of the better known agents from essential oils of thyme and clove oil or basil. They have been shown to inhibit the growth of a wide range of oral microorganisms including mutans streptococci, in vitro. Convincing data on their efficacy from in vivo studies, on the other hand is scarce (Agarwal. 2014).
• Ocimum sanctum aka "Tulsi": Tulsi, Ocimum sanctumis a plant of Indian origin and chances are youve already read its name. Its a time tested premier medicinal herb thats usually used diabetes mellitus, arthritis, bronchitis and skin diseases. Luckily tulsi does also have potent antimicrobial properties, against a whole variety of microorganisms like Staphylococus aureus, Klebsiella, candida albicans, E. coliandproteus sp.
  
  The antimicrobial activity of tulsi is attributed to its constituents namely ursolic acid and carvacrol. Agarwal et al. (Agarwal. 2010) in their study demonstrated an antimicrobial potential of tulsi extract at various concentrations and achieved maximum antimicrobial potential at 4% concentration level. Thats not much, but something we can work with... as only one ingredient of our toothpaste and mouth-wash, obviously ;-)

• Figure 1: Prunis is not as potent as  0.2% chlor- hexidine (CHX) and phosphate-buffered saline (PBS), but inhibits the growth of human oral keratinocytes within 5 minutes (Seneviratne. 2011)

  Prunus mume: Prunus mumeis is like Tulsi a TCM staple, It is, just like Tulsi not usually used for tooth hygiene.
  
  In vitro data from studies such as the one the data of which you see in Figure 1, would yet suggest that it is rightly considered to be a candidate for develo- ping an oral antimicrobial agent to control or prevent dental diseases associated with oral pathogenic bacteria like Strepto- coccus mutans, S. sobrinus, S. mitis, S. Sanguinis, Lactobacillus acidophilus, P. gingivalis, Aggregatibacter actino- mycetem comitans (Seneviratne. 2011)
• Green and black tea (Camellia sinensi): No reason to tell you what these are, right? Well, various component in green and black tea (leaves of Camellia sinensis), notably the simple catechins, have anticariogenic activity.
  
  Among the pathogens that have been shown to suffer from the exposure to these tea catechins are also S mutans and S sobrinus. In addition, there is evidence that tea does not only plaster your teeth with black tar, but that this black tar inhibits the adherence of bacteria to your teeth (lucky you ;-) - this works by the inhibition glucosyl transferase and the consequent reduction in biosynthesis of sticky glucan. And above all, a recent paper in the Journal of the Indian Society of Peridontologyconfirm sthe "effectiveness of green tea catechin mouthwash as an antiplaque agent" in man (Kaur. 2014).

• Oleic acid, Linoleic acid and epicatechin polymer fom Cacao bean husk: Have all been shown to have anti-cariogenic activity. Just like green tea, coffee and cacao, they inhibit the adherence of the bacteria to your teeth and best of all, there is even evidence that this stuff works - in rodents, at least (Ooshima. 2000; Osawa. 2001)
• Proanthocyanidins, phenolic acids, flavonols from Cranberry: These shows antimicrobial activity against biofilm cells of mutans streptococci. They will disrupt the acidogenic/aciduric properties of planktonic and biofilm cells of S. mutans and have rodent studies to back up their efficacy as in vivo inhibitors of caries development in rats infected with S. mutansis (Koo. 2002)
• Meswak chewing sticks (Twigs of Salvadora persica): The name already gives it away. This is another tool from traditional medicine, which is supposed to have been used by the Babylonians some 7000 years ago (Al Sadhan. 1999).

  Table 1: Miswak is not the only type of chewing stick thats used world-wide (Sukkarwalla. 2013)

  In this case, however, one that is in fact use to prevent caries! And in fact, the sticks have strong antibacterial effects against all relevant bacteria (Almas. 2004) - no wonder they have been used for tooth hygiene after being embedded in agar forever.
  
  What should be said, though, is that you could also use other anti-microbial substances as "toothpaste" on a Miswak stick, after youve made it bacteria proof with agar (agar is a polysaccharides that cannot be metabolised by bacteria).

  Figure 2: Marked reduction in levels of Streptococcus mutans in Miswak as compared to toothbrush users (left) and overview of Antimicrobial effects of Miswak (right; both from Sukkarwalla. 2013)

  Its effects, and the illusration in Figure 2 makes this quite clear, does still go way beyond the one of a classic toothbrush (Sukkarwalla. 2013).
• Trace elements: Actually, the initially mentioned fluoride would belong into this category as well... what? Yeah, you are right: Its note exactly smart to replace it with zinc, tin, aluminium, copper, iron, strontium, barium, manganese and molybdenum, gold, or lead, all of which have been investigated as weapons in our never-ending battle against tooth decay (hard to believe, I know).
  
  Of these trace elements, aluminum, copper, and iron have been used most commonly as cariostatic agents. Unfortunately, these agents are about as unhealthy for its user, as they are for the bacteria, when they are used in oral care products as simple salts. Moreover, the toxicity of many metals like aluminum, copper, barium molybdenum, would restrict the concentration at which they could be safely used.
• Propolis, the resinous mixture that honey bees collect from tree buds, sap flows, or other botanical sources: Propolis is a natural beehive product that serves a double purpose. It is used to make honey, and it keeps the hive bacteria-free.
  
  Propolis shows potent anti-bacterial activity against S. mutans and/or S. sobrinus in vitro ad has been used successfully as part of a a mouthwash with in vivo antimicrobial activity against S. mutans (Duailibe. 2007). Moreove, topical applications of chemically characterized Propolis extracts have also been shown to be highly effective in reducing the incidence and severity of smooth surface and sulcal caries in rats (Koo. 1999). 

• There are many other reports in the literature concerning the antimicrobial activities that various plant extracts may have against cariogenic bacteria, although the majority of these studies provide limited or incomplete information due to the lack of chemical characterization of the extracts. However, there are a few exceptions. For example, Li et al. (1999) have identified gallotannins from Melaphis chinensis and triterpenes (ceanothic acid and ceanothetric acid) from Ceanothus americanus as antimicrobial agents that harbor activity against mutans streptococci.
  
  Furthermore, a chemically characterized extract of Galla chinensis(containing gallic acid and methyl gallate) has been demonstrated to impede the growth of S. mutans and other caries- related organisms, including Lactobacillus rhamnosus and Actinomyces naeslundii, within biofilms. Recently, established that naturally occurring phenolic compounds generally display antibacterial activity by disrupting the membrane lipid-protein interface as nonionic surface-active agents (Greenberg. 2008) and  Ramakrishna et al. (2011) studied various natural alternatives derived from plants and plant products and concluded that it can serve as a prevention and treatment option against cariogenic bacteria. 

• They certainly dont look like it, but being filled with licorice extract, these lollipops are good for your teeth.

  Chinese Licorice Root: As a SuppVersity reader you know that it can help you lean out, by keeping your cortisol levels up(!). What you may have read as an aside, only, is that it will also help fight caries, if it is consumed as a "teeth hygiene lollipop" that contains a special herbal formula extracted from the Chinese licorice root.
  
  These orange flavoured herbal lollipops was discovered by microbiologist at the UCLA school of dentistry should be consumed twice a day- one in the morning after breakfast and another after professional teeth cleaning between two and four times a year (Agarwal. 2010). 
• Xylitol: Xylitol is last on the list, and probably an agent may of you know. Its - unlike most people think - 100% natural and was first used as a tooth-friendly sweetener in chewing gums, lollipops and other stuff more than 80 years after its discovery in 1891 by German chemist Emil Fischer.
  
  Dental benefits of xylitol were first recognized in Finland in 1970 using animal models. The first chewing gum developed with the aim of reducing caries and improving oral health was released in Finland in 1975 and in United States shortly after. Xylitol is not fermented by cariogenic plaque bacteria and thus does not lower the pH of the plaque. It reduces the accumulation of plaque on the surface of the tooth.
  
  In contrast to many other marketing claims the efficacy of xylitol based chewing gum is scientifically established (Isokangas. 1987) and its effect to inhibit enamel dissolution, another claim you may have heard already has in vitro data to back it up (Arends. 1990). In children reporting caries experience, consumption of xylitol containing lozenges or hard candy reduces incidence of coronal caries (Alanen. 2000).
  
  For children below age two, in addition to the study that evaluated xylitol tablets, the xylitolcontaining syrup among children in the Marshall Islands and reported a statistically significant difference in favor of xylitol syrup (Milgrom. 2009) - for children unde rthe age of 2, on the other hand, there is insufficient evidence that xylitol syrup prevents caries. The same lack of convincing evidence exists with respect to xylitol dentrifrice, of which we cannot tell if its the xylitol or another agent thats responsible for the inhibition of dental caries.

Reference:

• Agarwal, Pooja, and L. Nagesh. "Evaluation of the antimicrobial activity of various concentrations of Tulsi (Ocimum sanctum) extract against Streptococcus mutans: An in vitro study." Indian Journal of Dental Research 21.3 (2010).
• Agarwal, R., et al. "Prevention of Dental Caries-Measures beyond Fluoride." Oral Hyg Health 2.122 (2014): 2332-0702.
• Al Sadhan, Raed I., and Khalid Almas. "Miswak (chewing stick): a cultural and scientific heritage." Saudi dental journal 11.2 (1999): 80-87. 
• Alanen, Pentti, Pauli Isokangas, and Kristjan Gutmann. "Xylitol candies in caries prevention: results of a field study in Estonian children." Community dentistry and oral epidemiology 28.3 (2000): 218-224.
• Arends, J., et al. "Combined effect of xylitol and fluoride on enamel demineralization in vitro." Caries Research 24.4 (1990): 256-257.
• Duailibe, Silvana Alves de Carvalho, Azizedite Guedes Gonçalves, and Fernando Jorge Mendes Ahid. "Effect of a propolis extract on Streptococcus mutans counts in vivo." Journal of Applied Oral Science 15.5 (2007): 420-423. 
• Greenberg, Michael, Michael Dodds, and Minmin Tian. "Naturally Occurring Phenolic Antibacterial Compounds Show Effectiveness against Oral Bacteria by a Quantitative Structure? Activity Relationship Study." Journal of agricultural and food chemistry 56.23 (2008): 11151-11156. 
• Isokangas, Pauli. "Xylitol chewing gum in caries prevention. A longitudinal study on Finnish school children." Proceedings of the Finnish Dental Society. Suomen Hammaslääkäriseuran toimituksia 83 (1987): 1.
• Kaur, H., S. Jain, and A. Kaur. "Comparative evaluation of the antiplaque effectiveness of green tea catechin mouthwash with chlorhexidine gluconate." Journal of Indian Society of Periodontology 18.2 (2014): 178.
• Koo, H., et al. "Effect of Apis mellifera propolis from two Brazilian regions on caries development in desalivated rats." Caries Research 33.5 (1999): 393-400. 
• Li, Xing-Cong, Linin Cai, and Christine D Wu. "Antimicrobial compounds from< i> Ceanothus americanus</i> against oral pathogens." Phytochemistry 46.1 (1997): 97-102.
• Ooshima, T., et al. "Caries inhibitory activity of cacao bean husk extract in in-vitro and animal experiments." Archives of Oral Biology 45.8 (2000): 639-645.
• Osawa, K., et al. "Identification of cariostatic substances in the cacao bean husk: their anti-glucosyltransferase and antibacterial activities." Journal of Dental Research 80.11 (2001): 2000-2004.
• Ramakrishna, Y., et al. "Decreasing cariogenic bacteria with a natural, alternative prevention therapy utilizing phytochemistry (plant extracts)." Journal of Clinical Pediatric Dentistry 36.1 (2011): 55-64.
• Seneviratne, Chamida J., et al. "Prunus mume extract exhibits antimicrobial activity against pathogenic oral bacteria." International Journal of Paediatric Dentistry 21.4 (2011): 299-305. 
• Sukkarwalla, Adnan, et al. "Efficacy of Miswak on Oral Pathogens." Dental research journal 10.3 (2013): 314.
• Taylor, Peter W., J. M. Hamilton-Miller, and Paul D. Stapleton. "Antimicrobial properties of green tea catechins." Food science and technology bulletin 2 (2004): 71-81.