Lack of Sun Exposure & Type II Diabetes - Contemporary Evidence Suggests: There is a Link!

"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, it's 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, that's 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".

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Pre-Workout Supps Could Ruin Your Sleep

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" - that's 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 it's 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).

But sunlight gives you skin cancer, right? If you are the typical white-skinned tourist who grills in the sun for 8h a day in his 2-week beach holiday (=intermittent high exposure), yes! A chronic exposure to a moderate doses of sunlight, on the other hand, has been associated with a significant 27% reduced risk of melanoma (Nelemans. 1995).

Since physical activity may follow a similar circannual rhythm, it's 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.

Circadian Rhythmicity - Sunlight a La Carte: How to "Hack" Your Circadian Rhythm With 30min of Light Therapy Per Day | more

Bottom line: All in all, it appears to be likely that a lack of direct and regular moderate sun exposure is among the many lifestyle factors that increase your risk of developing type II diabetes.

The ameliorative effects of obesity, researchers like Lindqvist et al. (compare Figure 2) have observed, on the other hand, should remind you that you won't get away with "just" getting enough sun exposure. Regular physical activity and a whole foods diet for obesity prevention are at least as important as the hours you spend in the sun | Comment on Facebook!

Speaking of hours in the sun, the overall beneficial effects are more likely to be related to the beneficial effects of sun exposure on circadian rhythmicity than on its effect on other chemical processes, such as the formation of vitamin D.

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. 

Fat From Serotonin. MS Despite Vitamin D. DHA & DPA Feel at Home in Your Cellwalls. Weightloss Obstacle Late Lunch? Wrist Predicts Diabetes Risk. Viagra Detoxes the Brain. Acetyl Cysteine Battles Acne. Propolis Increases GLUT-4

Yet another reason why calorie counting is not good for your sanity: The "average" sexual intercourse burns only 14 kcal more than watching TV.  and significantly less than a fast paced walk on the inclined treadmill. Luckily weight loss & maintenance is more complex than calories in vs. out, anyway ;-)

"14" that's the SuppVersity figure of the number of extra calories you will expend when you and your significant other decide to have sex instead of sitting on the couch watching TV tonight. I got that figure from a paper my buddy Sean Casey from CasePerformance has brought to my attention. Published in the latest issue of the prestigious New England Journal of Medicine (Casazza. 2013), it discusses the 7 most commonly held "false and scientifically unsupported beliefs about obesity" the scientists identified in a thorough analysis of popular media and scientific literature.

"The scientific community needs some more honesty"

While the sex-myth, which originally states that you would burn at least 100kcal, with a little more action"" even 300kcal per intercourse, is obviously my favorite, there are also a couple of  less sexy "presumptions about obesity" (e.g. simply eat more veggies and fruit and you lose weight) and "facts about obesity" (e.g.  the scientists dug up and debunked in a paper that ends with the wise words:

"While we work to generate additional useful knowledge, we may in some cases justifiably move forward with hypothesized, but not proved, strategies. However, as a scientific community we must always be open and honest with the public about the state of our knowledge and should rigorously evaluate unproved strategies." (Casazza. 2013)

Actually the term "the state of our knowledge" is an ideal segue to what follows - the "short" news! Originally the On Short Notice column was actually intended as a very brief overview over what has been going on in the "community" as of late. And since we are talking about honesty, I must admit that I have failed miserably in the past installments as far as the tiny word "short" in the column's title is concerned. 

The new short news are short again ;-)

So, as of now, I will be doing my very best to bring the On Short Notice column back on the short track, so to say. I guess, we will see in a couple of paragraphs, how successful my efforts will be ;-)

• Does serotonin make you fat? It's pro-fat storage effects would suggest so
  
  

  

  If 5-HT can make you fat and creatine blunts its increase PWO (learn more), what does that tell us about creatine? Nothing, but it leaves room for speculations.

  (Gres. 2013) -- If you trust in TV wisdom the reason women eat chocolate, whenever they feel sad or alone is it's ability to boost serotonin (5-HT). The latter is yet not the reason Sandra Grès et al. say that serotonin could make you fat. Rather than that, it's the ability of 5-HT to stimulate the obesogenic peroxisome proliferator-activated receptor γ (PPAR-γ, learn more), on adipose cells, which will increase fat storage and the recruitment of new fat cells from the stem cell reservoir.
  
  These effects happen in the periphery (vs. the brain) and are totally unrelated to the centrally mediated effects of serotonin.

• MS patients benefit from the sun, not vitamin D
  
  (Zivadinov. 2013) -- Where is your vitamin D supposed to come from? From your skin, right. And where does your skin get it from? From tablets? No. It manufactures it from the "bad" cholesterol, when it's  exposed to the "bad" sunlight.
  
  

  

  In the upper left of this image you see, where the magic is - the rest is just a nice bonus.

  With all those supposedly bad, but in fact vital things being important for much more than vitamin D synthesis it is therefore not surprising that a recently published paper on the asociations of sun-exposure and/or vitamin D with MRI measures in multiple-sclerosis patterns revealed that
  

  "[...] sun exposure was associated with increased grey matter volume (GMV, r_p=0.16, p=0.019) and whole brain volume (WBV, r_p=0.20, p=0.004)" (Zivadinov. 2013).

  ...and that totally irrespective of whether the subjects had high or low vitamin D levels. If you wanted to say it fancily, you'd say the beneficial effects of sun exposure on the brain volume in MS patients was found to be disassociated from the effect the sun has on vitamin D levels (suggested read: Vitamin D, Epstein Bar & MS)

• If you want to up the omega-3 levels in your tissue, pick DHA and / or its precursor DPA over EPA
  
  

  

  Figure 1: Incorporation various lipid fractions in different tissues (Kaur. 2013)

  (Kaur. 2013) -- According to a very recent rodent study docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) are much more readily incorporated into two of your most vital organs, namely your brain and liver and likewise the preferred phospholipid in the cell walls of your kidneys and muscle tissue. Only your fat cells don't really like these long(est) chain omega-3s the incorporation of which was ~50% lower than that of oleic acid (OA; that's the mono-unsuaturated fatty acid in olive oil), which was used as a "neutral" control.
  
  The one question I would still like to have an answer to is how beneficial it actually is, if the phospholipids (PL, figure 1) in your cell membranes are full of easily oxidizable fatty acids.
  
  Also, what do we make of the other lipid fractions? Cholesterol (CHOL), diacylglycerol (DGL) and NEFAs + triglycerides (NE+TG)? Where do we actually want those good omega-3 fatty acids to accumulate? ... just some food for thought  for your DPA and DHA lovin' brains ;-)

• 
  On a side note: If you like GMO, you won't have to eat fish any longer to get your omega-3 PUFAs
  
  (Petrie. 2012) -- Researchers from the CSIRO Food Futures National Research Flagship have already engineered the first GMO brassica species with a higher DHA yield >11% than fish. The invention is hailed as "a breakthrough in the development of sustainable alternative sources of DHA as this technology should be applicable in oilseed crops" (Petrie. 2012)

• When late eating (spec. lunch) and certain genes come together weight loss can become pretty difficult - reasons still not fully understood, though
  
  (Garaulet. 2013) -- Late lunch and certain genotypes appear to make weight loss difficult for some. And the relation holds even after possible confounding factors like energy intake and even appetite hormones, were measured.
  

  

  Skipping breakfast. Yay or Nay? (read more)

  "Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups." (Garaulet. 2013)

  While this is not a general argument against intermittent fasting, skipping breakfast and thelike, it does still go to show you that we are not all created exactly equal and any cookie cutter approach to weight loss therefore counter-indicated. 

• Show me your wrist and I'll tell you something about your glucose metabolism.
  
  (Nudeh. 2013) -- A study that was published in the latest issue of the The Journal of Clinical Endocrinology & Metabolism reveals: Wrist circumference is a significant predictor of diabetes in both genders of adult population.

  

  Figure 2: Incidence of diabetes during 8.8 years of follow-up in different tertiles of baseline
  wrist circumference among male and female populations (significant trend in both genders; Noudeh. 2013)

  What's particularly interesting is that this association which was observed in cohort of 6393 subjects (2716 males and 3677 females), who had been subjected to a standard 2-hour postchallenge plasma glucose, test holds independent of BMI and waist circumference - allegedly in women, only. 

• Sildenafil Citrate Attenuates the Deleterious Effects of Elevated Ammonia
  
  (Arafa. 2013) -- You will probably remember the problems with ammonia accumulation due to huge BCAA and protein intakes (learn more). If you trust the latest results of two Egyptian researchers from the Zagazi University it would look as if a solution to that problem (which shouldn't be one, if your liver is healthy and you don't go overboard on pro-ammonia foods, anyway) would already exist: Sildenafil citrate aka Viagra can help.
  
  In their study the researcher administered 10mg/kg sildenafil to rats that were treated with daily intraperitoneal (i.p.) injection of ammonium chloride (100 mg/kg body weight) for eight weeks. This treatment resulted in a significant reduction in serum liver enzymes, lipid profile and - maybe most importantly - brain lipid peroxidation and caspase-3 mRNA. It also increased the nitric oxide (NO) levels in the blood and lead to a significant increase in cGMP, antioxidants and endothelial nitric oxide synthase (eNOS) gene expression in the brains of hyperammonemic rats.
  

  

  List of various foods and their ammonia content (Rudnan. 1973)

  "Our results showed that sildenafil exerts a protective effect on the brain by reversing oxidative stress during hyperammonemia and this could be due to (i) cytoprotective, antioxidant and anti-apoptotic effects ii) increasing cGMP and enhancing the proper metabolism of fats which could suppress oxygen radical generation and thus preventing oxidative damage in the brain."

  Until now, the scientists cannot tell how exactly the human equivalent of 1.62mg/kg sildenafil citrate work, but its modulatory effect on the NO/cGMP pathway is the most likely candidate. That these effects are of real world significance has incidentally been shown, already. In 2003, for example, the learning abilities of rats with hyperammonia was restored by a similar regimen (Erceg. 2003) 

• Acetyl cysteine - don't swallow, but rub it... onto your skin, if you have acne
  
  (

  

  The comedo count is a measure of the number of comedones, i.e. the open black "pores" like those on the forehead of the person shown on this photo

  Montes. 2012) -- According to a study published in the latest issue of Skinmed, the application of a 5% acetylcysteine topical gel proved to be "significantly superior to placebo (P = .04)" in reducing the comedo counts. The results were comparable in  male and female participants and would suggest that "acetylcysteine is an effective therapeutic option for the treatment of mild to moderate acne". Whether it is an alternative to the retinoid based standard drugs, is yet still questionable.
  
  By the way, the latter, or rather the most prescribed of these retinol-like drugs, namely tretinoin has only recently been found to synergize with Aloe vera for even better results (Saeedi. 2013).

• Brazilian propolis ethanol extract promotes glucose uptake and translocation of insulin-sensitive glucose transporter (GLUT) 4 in skeletal muscle
   
  

  

  In the unfortunate case you missed the news: The commonly ignored BCAA Isoleucine also boosts GLUT4 (read more)

  (Ueda. 2013) I guess you will have heard about the miracles "royal jelly" is supposed to work on your health, right? Well, the cheap "packaging" material bees use to seal the smaller gaps in their hives (the larger ones are usually filled with beeswax) seems to have similarly outstanding - and in this case scientifically backed effects.
  
  When propolis was administered at a human equivalent dose of 20mg/kg to mice, those rodents saw increases in both PI3 and AMPK modulated increase in the glucose transporter 4 activity and skeletal glucose uptake.
  
  The main active polyphenols were artepillin C, coumaric acid, and kaempferide. All of them promoted GLUT4 translocation in a subsequent ex-vivo analysis using L6 myotubes, but kaempferide, which can also be found in acovado seeds (Pahua-Ramos. 2012) and cordia sinensis aka  grey-leaved saucer berry extracts (Martinetti. 2010), was the most potent one.

Now you are surprised, right? Me too. Nine individual items and all of them still qualify as "short news". I guess in view of the sheer abundance of news you won't need anything else till tomorrow, but in case you do, I have a couple of suggestions to check out on the SuppVersity Facebook Wall:

• Lycopene works as an anti-cancer agent, because some of it's metabolites "look" like retinol (vitamin A) and dock to the retinol receptor (read more)
  
• Curcumin is a hormetic agent (learn more about hormesis), but not all curcuminoids are created equally effective (read more)
• White poison!? Low sugar diet does not improve insulin sensitivity but decreases glucose levels in obese subjects (read more)
• Myostatin knockout mice have increased brown fat - Does this mean that myostatin suppression will increase browning of fat in man, as well? The recent SuppVersity article on PGC-1A4 already confirmed that (read more) 
• Fish oil for alcohol withdrawal - Only three weeks on low dose EPA (60 mg/day) and high dose DHA (252 mg/day) supplement yielded significant decreases in distress symptoms and basal cortisol secretion in abstinent alcoholics (read more)
• SuppVersity Suggested Read: The Hunter-Gatherer Within: Health and the Natural Human Diet - "Don't get your food from the same place your car does" (read more)

There are going to be a couple of more news before the official next SuppVersity post will be posted in ~24h - so "like" the SuppVersity on Facebook and make sure you don't miss any of them. Have a nice weekend!

References:

• Arafa MH, Atteia HH. Sildenafil Citrate Attenuates the Deleterious Effects of Elevated Ammonia. Toxicol Mech Methods. 2013 Jan 23. 
• Casazza K, Fontaine KR, Astrup A, Birch LL, Brown AW, Bohan Brown MM, Durant N, Dutton G, Foster EM, Heymsfield SB, McIver K, Mehta T, Menachemi N, Newby PK, Pate R, Rolls BJ, Sen B, Smith DL Jr, Thomas DM, Allison DB. Myths, presumptions, and facts about obesity. N Engl J Med. 2013 Jan 31;368(5):446-54.
• Erceg S, Monfort P, Hernández-Viadel M, Rodrigo R, Montoliu C, Felipo V. Oral administration of sildenafil restores learning ability in rats with hyperammonemia and with portacaval shunts. Hepatology. 2005 Feb;41(2):299-306.
• Garaulet M, Gómez-Abellán P, Alburquerque-Béjar JJ, Lee YC, Ordovás JM, Scheer FA. Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond). 2013 Jan 29.
• Grès S, Canteiro S, Mercader J, Carpéné C. Oxidation of high doses of serotonin favors lipid accumulation in mouse and human fat cells. Mol Nutr Food Res. 2013 Feb 6.
• Jahangiri Noudeh Y, Hadaegh F, Vatankhah N, Momenan AA, Saadat N, Khalili D, Azizi F. Wrist Circumference as a Novel Predictor of Diabetes and Prediabetes: Results of Cross-Sectional and 8.8-Year Follow-up Studies. J Clin Endocrinol Metab. 2013 Feb;98(2):777-84.
• Kaur G, Molero JC, Weisinger HS, Sinclair AJ. Orally administered [14C]DPA and [14C]DHA are metabolised differently to [14C]EPA in rats. British Journal of Nutrition. 2013; 109, pp 441-448. 
• Martineti V, Tognarini I, Azzari C, Carbonell Sala S, Clematis F, Dolci M, Lanzotti V, Tonelli F, Brandi ML, Curir P. Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus. Phytother Res. 2010 Sep;24(9):1302-8.
• Montes LF, Wilborn WH, Montes CM. Topical acne treatment with acetylcysteine: clinical and experimental effects. Skinmed. 2012 Nov-Dec;10(6):348-51.
• Pahua-Ramos ME, Ortiz-Moreno A, Chamorro-Cevallos G, Hernández-Navarro MD, Garduño-Siciliano L, Necoechea-Mondragón H, Hernández-Ortega M. Hypolipidemic effect of avocado (Persea americana Mill) seed in a hypercholesterolemic mouse model. Plant Foods Hum Nutr. 2012 Mar;67(1):10-6.
• Petrie JR, Shrestha P, Zhou XR, Mansour MP, Liu Q, Belide S, Nichols PD, Singh SP. Metabolic engineering plant seeds with fish oil-like levels of DHA. PLoS One. 2012;7(11):e49165. 
• Rudnan D, Smith RB 3rd, Salam AA, Warren WD, Galambos JT, Wenger J. Ammonia content of food. Am J Clin Nutr. 1973 May;26(5):487-90.
• Ueda M, Hayashibara K, Ashida H. Propolis extract promotes translocation of glucose transporter 4 and glucose uptake through both PI3K- and AMPK-dependent pathways in skeletal muscle. Biofactors. 2013 Jan 28.
• Zivadinov R, Treu CN, Weinstock-Guttman B, Turner C, Bergsland N, O'Connor K, Dwyer MG, Carl E, Ramasamy DP, Qu J, Ramanathan M. Interdependence and contributions of sun exposure and vitamin D to MRI measures in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Feb 5.