Download Fitness Tools

With the right diet and lifestyle, stem cell treatments, probiotic supplements or xylose-laden "functional foods" wouldn't be necessary in the first place.

You're probably used to it, but I am in the mood for bragging: The waredownloadsoft is where you'll read about the latest nutrition, exercise and supplement related studies first. In research updates like the one today, I am trying to provide a little more information than in the SV Facebook News, though, where I usually stick only to the main results of studies that have just been published or at least accepted for publication.

In today's installment of what I often call the "Short News", I will discuss three papers that are going to be published in one of the next issues of the peer-reviewed scientific journal Nutrition News.

Studies dealing with a pre-clinical, but promising stem cell therapy for diabetics, the verdict on probiotic supplements (including my evaluation of the scientists' verdict ;-) for weight loss and an update on the effects of the xylitol precursor d-xylose and its effect on mammalian fat cells in vivo.

• Stem Cells as Diabetes Treatment (Xing. 2015) - In software development you'd probably call the latest study from the Cangzhou City Central Hospital an "early alpha version" of an intriguing new way of treating type II diabetes.
  
  In their latest rodent study, Baoheng Xing et al. build on previous experiments in which pancreatic progenitors derived from human embryonic stem cells were shown to be able to effectively treat diabetes in mice (Kroon. 2008). In their study, however, Xing et al. went one step further and developed a system for treating diabetes using human embryonic stem cell–derived pancreatic endoderm in a mouse model of gestational diabetes mellitus.
  

  Figure 1: Glucose (a), insulin (b) and body weight (c) levels of wild type (wt) and treated (db/+PE) vs. untreated (db/+) pregnant mice before and during gestation, as well as Kaplan-Meier survival curves of litters show significant improvement right into the normal range in response to treatment (Xing. 2015)

  To this ends, the researchers had human embryonic stem cells differentiate in vitro into pancreatic endoderm, which were then transplanted into db/+ mice suffering from gestational diabetes mellitus.
  
  As the data in Figure 1 goes to show you, the transplant, of which the researchers expect that it could be used in humans, too, greatly improved the glucose metabolism and reproductive outcome of the treated female rats compared with the control groups. With their results Xing et al. do thus contribute to the growing evidence that diabetes may (sooner or later) be a "curable" disease when we are eventually mastering the use of differentiated human embryonic stem cells for treating general and gestational diabetes mellitus patients.
• Probiotics and weight loss - reviewed (Park. 2015): What's the verdict? You will remember that I am still skeptical with respect to the real world benefits of the new en-vogue supplements that contain billions of life or dead bacteria and promise benefits from increased gut health to... you guessed it, the most marketable of all benefits: weight loss!
  
  A recent systematic review by scientists from the Hoseo University and the Keimyung University in Korea presents the first attempt to summarize and critically evaluate the evidence from clinical trials that have tested the effectiveness of probiotics or foods containing probiotics as a treatment for weight loss. Literature searches of electronic databases such as PubMed, Cochrane Library, and EMBASE were conducted. Methodological quality was assessed using body weight and body mass index (BMI). Initial searches yielded 368 articles. Of these, only 9 met the selection criteria. Because of insufficient data, only 4 of the studies were randomized controlled trials (RCTs) that compared the therapeutic efficacy of probiotics with placebo.
  
  As my skepticism would have made me believe, the meta-analysis of these data showed no significant effect of probiotics on body weight and BMI (body weight, n = 196; mean difference, −1.77; 95% confidence interval, −4.84 to 1.29; P = .26; BMI, n = 154; mean difference, 0.77; 95% confidence interval, −0.24 to 1.78; P = .14).
  

  Figure 3: It's not like there were no benefits. You just have to look at the right parameters to see them. Studies like Kadooka et al. show that the effects on BMI are small compared to those on metabolically more relevant markers like total fat mass, waist circumference and visceral fat (Kadooka. 2015).

  That does not mean that there are no benefits at all, though. I reviewed the few studies that measured not just body weight and BMI, but also the subjects' body fat levels. This is an important difference, because a focus on BMI ignores potentially health relevant changes in body composition. Changes as they were observed by Kadooka et al. (2013; see Figure 3), for example, who found a significant time x group differences for visceral fat, fat percentage, fat mass, and waist circumference with much less pronounced effects on BMI (too low to influence the result of a systematic review significantly) in their 12-week study. In this context, it is also worth mentioning that Sanchez et al. (2014) observed a significant beneficial effect in obese women (but not man) for whom the consumption of 1.6 × 10^8 colony-forming units of LPR/capsule with oligofructose and inulin made it significantly easier to maintain their body weight after a weight loss intervention. Another benefit that must not be ignored.

• Overall, I still feel obliged to repeat what I wrote in my recent article on the effects of sweeteners on the microbiome: We still have to learn very much about the effects of probiotics in general and individual types of gut bacteria, in particular, before we can actually give good strain-specific supplement recommendations. It's after all possible that the same strains that work in the obese subjects of studies like Kadooka (2015) won't work or even do the opposite in lean individuals.
• D-Xylose Exerts Epigenetic Anti-Obesity Effects and Stops Fat Cell Growth (Lim. 2015) - Yes, this is not the first study to show that the provision of D-Xylitol or, as in the case of a 2011 study by Amo,et al., its cousin and "artificial sweetener" xylitol can reduce the weight gain due to obesogenic diets. What makes it interesting, though, is that it involved two different, relatively low dosages of D-xylitol as they could easily be added to our own food chain.
  

  Figure 4: While the effects on body weight and fat gain were significant, the differences (expressed relative to the rodents on regular chow) are still significant, so even if you replace 5-10% of the sugar in your junkfood diet with the low calorie sweetener (2.4kcal/g), you will get fat. If anything it may completely prevent the increase in liver fat - albeit only if the dosage is high enough and the effects are identical in humans (data from Lim. 2015)

  With only 5% and 10% of the sucrose content of the high fat chow of the rodents in Lim et al.'s latest study being replaced by D-Xylose, the scientists observed
  • significant reductions in weight and more importantly fat gain
  • significant reductions in hepatic steatosis (NAFLD),
  • a reduction of the genes that are responsible for the storage of fat to normal (5%) and sub-normal (10% D-Xylose) levels, and
  • significant reductions in total cholesterol and low-density lipoprotein cholesterol, low-/high-density lipoprotein, and the important total cholesterol/high-density lipoprotein ratio.
  In view of the fact that replacing just a relatively small amount of sucrose in our diet with D-Xylose (and probably xylitol) can ameliorate the weight and adipose tissue gain, normalize blood glucose levels and blood lipid profiles and lower the lipid accumulation in the liver by "regulating expression of lipogenesis- and β-oxidation–related genes" (Lim. 2015), it is probably actually warranted to speculate, just like Lim et al., about a "possible application of d-xylose as a dietary supplement for the prevention of obesity-related metabolic disorders" (Lim. 2015) - even though clinical human trials are still warranted.

Seafood is an excellent source of iodine, but many people get most of their iodine from iodized table salt.

I assume you would have expected me to forget that I promised to do my very best to turn the "too much of a good thing" article on selenium I wrote a week ago into a series, right? Well, you obviously don't know me well enough, then, because here's installment #2 of this new series. One that is closely related to #1, but was significantly more difficult to write.

Why's that? Well, if you took a look at the literature discussing the effects of iodine supplementation on thyroid function, you'd know why it was ... well, "complicated" and not exactly unambigous to say the least.
In view of the fact that it would go beyond the scope of any single article to discuss the detailed effects of iodine and iodine supplements in the various thyroid disease states, I will focus solely on the beneficial and detrimental effects of iodine in more or less healthy individuals. Furthermore, I will not go into details as far as...

• Table 1: The spectrum of iodine deficiency disorders - click to see all (Delange. 1994)

  the important role of iodine in brain and general physical development and the ~30% increase in iodine requirements in pregnant women (Delange. 2000; Zimmermann. 2004 & 2011),
• the role of iodine in psychiatric disease (Hetzel. 2000), and
• the influence of (inorganic) iodine in the environment on human / general mammalian health (Fuge. 1987)

are concerned. What I would like to mention, at least, is the often-cited role of iodine in breast cancer, because the purported protective effect of iodine from supplements or food (Cann. 2000; Funahashi. 2001) is one of the reasons many women consume iodine supplements in dosages that could be more of a threat than a blessing for their health. That's bad news in view of the fact that the "evidence" of breast cancer protective effects is still in the hypothetical state and "rigorous retrospective and prospective studies are needed to confirm this hypothesis" (Cann. 2000).
Things we can say about iodine that are above all relevant for both, men and women, is that it is essential for normal thyroid function. Just as it is the case for selenium (discussed in the last installment of this series), though, the effects of supplemental iodine on thyroid function are far from being conclusive. While a lack of iodine will force the thyroid to increase it's efficacy by - eventually - developing goiterous growth, the dietary and even more so the supplemental ingestion of copious amounts of iodine (>1mg) do something most people won't expect: They reduce the function of the thyroid glands.

Figure 1: On a population-based study, high(er) iodine intakes are associated with higher TSH levels and thus reduced thyroid function, while high intakes are associated with increased TSH and reduced thyroid fct. (Laurberg. 1998).

It is thus not surprising that populations with low and high iodine intake tend to develop opposite thyroid disorders with

• goiter and thyroid hyperfunction being more prevalent among populations with low(er) iodine intakes, and 
• impaired thyroid function (=subclinical and clinical hypothyroidism) being more prevalent among populations with relatively high iodine intakes (Lauerberg. 1998). 

This does not mean, that "half-deficient" intakes were best, even though there's evidence that a mild = non-goitrogenic iodine deficiency partly protects against autoimmune thyroid disease (Laurberg. 1998). In that US scientists warn that it is not sure, in how many cases the iodine induced reduction in thyroid function "may result from the adverse effect of excess iodine on thyroid function in persons with underlying thyroid disease such as Hashimoto’s thyroiditis, history of subacute thyroiditis, or silent postpartum lymphocytic thyroiditis" (Hollowell. 2002).
It is thus all the more important to take the little experimental evidence there is into consideration. In that, the often-seen drops in thyroid function in response to the ingestion of large quantities of iodine are often ascribed to the so-called Wolff-Chaikoff which is supposed to reduce the thyroid function for no longer than a few a days and then, through the so-called "escape" phenomenon, the organification of intrathyroidal iodide resumes and the normal synthesis of thyroxine (T4) and triiodothyronine (T3) returns (Markou. 2001). Now, the problem is: The phenomenon is not always as short-lived as it is supposed to be

Table 2: Taking high amounts of iodine can significantly reduce thyroid function or induce goiter. Specifically in the subgroups of the population mentioed above (Roti. 2000)

"in a few apparently normal individuals, in newborns and fetuses, in some patients with chronic systemic diseases, euthyroid patients with autoimmune thyroiditis, and Graves' disease patients previously treated with radioimmunoassay (RAI), surgery or antithyroid drugs, the escape from the inhibitory effect of large doses of iodides is not achieved and clinical or subclinical hypothyroidism ensues [and may require temporary or permanent treatment with thyroid medications]" (Markou. 2001). 

Even if you believe you know you don't suffer from any of the aforementioned thyroid problems taking 10mg or more of iodine may be likened to Russian Thyroid Roulette, because it always entails the risk of iodide-induced hypothyroidism. Usually the hypothyroidism is transient and regresses within 2-3 weeks after iodide withdrawal, but as Markou et al. highlight there's a small subgroup of patients who develop transient iodine-induced hypothyroidism that must be followed long term thereafter because many will develop permanent primary hypothyroidism.

Figure 2: People with a previous history of painful subacute thyroiditis (SAT) are highly susceptible to the hypothyroid effects of 300mg/day iodine compared to people who had surgery for benign thyroid nodules (Roti. 1990).

Overall, it should be noted, though that the human body is pretty good at managing high intakes of iodine. While iodine-induced hypothyroidism was also reported in patients with no apparent thyroid disease the number of scientifically verified reports like the mild reversible hypothyroidism that was observed in elderly patients consuming iodinated glycerol by Drinka et al. (1998) or the two Japanese patients with anorexia nervosa developed iodine-induced hypothyroidism after they had consumped of large quantities of OshaberiKombu, a Japanese food that is extensively consumed on lowe energy diets and contains approximately 13.4 mg of iodine per 100g (Matsubayashi. 1998).

All in all the aforementioned examples are yet the exception to the rule. A rule which is evidenced in studies like Markou et al. (2000), in which the authors administered 80 mg potassium iodide (which is also the form of "iodine" in Lugol's solution) to 30 normal children 8 to 14 years old for 3 months and found that none developed overt or subclinical hypothyroidism. That does not mean that the iodine was without effect, but what the scientists observed was the expected transient elevation in serum TSH values (5–8 mU/L) as a result of the Wolff-Chaikoff effect. An effect that abated without further medical intervention on part of the researchers after 3-4 weeks when the TSH returned to normal levels despite the continuation of iodide treatment (Markou. 2000).
References:

• Cann, Stephen A., Johannes P. van Netten, and Christiaan van Netten. "Hypothesis: iodine, selenium and the development of breast cancer." Cancer Causes & Control 11.2 (2000): 121-127.
• Caldwell, Kathleen L., et al. "Iodine status of the US population, National Health and Nutrition Examination Survey, 2005–2006 and 2007–2008." Thyroid 21.4 (2011): 419-427.
• Delange, François. "The disorders induced by iodine deficiency." Thyroid 4.1 (1994): 107-128.
• Delange, Francois. "The role of iodine in brain development." Proceedings of the nutrition society 59.01 (2000): 75-79.
• Denef, Jean-François, Marie-Christine Many, and M. F. van Den Hove. "Iodine-induced thyroid inhibition and cell necrosis: two consequences of the same free-radical mediated mechanism?." Molecular and cellular endocrinology 121.1 (1996): 101-103.
• Drinka, Paul J., and Wolfram E. Nolten. "Effects of iodinated glycerol on thyroid function studies in elderly nursing home residents." Journal of the American Geriatrics Society 36.10 (1988): 911-913.
• Fuge, R. "Iodine in the environment: its distribution and relationship to human health." Trace substances in environmental health-XXI. 1987.
• Funahashi, Hiroomi, et al. "Seaweed prevents breast cancer?." Cancer Science 92.5 (2001): 483-487.
• Hetzel, Basil S. "Iodine and neuropsychological development." The Journal of nutrition 130.2 (2000): 493S-495S.
• Hollowell, Joseph G., et al. "Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)." The Journal of Clinical Endocrinology & Metabolism 87.2 (2002): 489-499.
• Laurberg, Peter, et al. "Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark." The Journal of Clinical Endocrinology & Metabolism 83.3 (1998): 765-769.
• Many, Marie-Christine, et al. "In vitro study of acute toxic effects of high iodide doses in human thyroid follicles." Endocrinology 131.2 (1992): 621-630.
• Matsubayashi, Sunao, et al. "Iodine-induced hypothyroidism as a result of excessive intake of confectionery made with tangle weed, Kombu, used as a low calorie food during a bulimic period in a patient with anorexia nervosa." Eating and Weight Disorders-Studies on Anorexia, Bulimia and Obesity 3.1 (1998): 50-52.
• Markou, K., et al. "Effects of chronic iodide administration in thyroid function in children and adolescents with a history of transient congenital hypothyroidism." 27th Annual Meeting, Greek Endocrine Association, Nicosia Cyprus. Vol. 82. 2000.
• Roti, Elio, et al. "Iodine-Induced Hypothyroidism in Euthyroid Subjects with a Previous Episode of Subacute Thyroiditis*." The Journal of Clinical Endocrinology & Metabolism 70.6 (1990): 1581-1585.
• Roti, E., and A. G. Vagenakis. "Effect of excess iodide: clinical aspects." Werner and Ingbar’s The Thyroid–Braverman LE and Utiger RD. Ed, Lippincott (2000): 316-329.
• Sang, Zhongna, et al. "Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial." The American journal of clinical nutrition 95.2 (2012): 367-373.
• Zanzonico, Pat B., and David V. Becker. "Effects of time of administration and dietary iodine levels on potassium iodide (KI) blockade of thyroid irradiation by 131I from radioactive fallout." Health Physics 78.6 (2000): 660-667.
• Zimmermann, M., and F. Delange. "Iodine supplementation of pregnant women in Europe: a review and recommendations." European Journal of Clinical Nutrition 58.7 (2004): 979-984.
• Zimmermann, Michael B. "The role of iodine in human growth and development." Seminars in cell & developmental biology. Vol. 22. No. 6. Academic Press, 2011.

Since the natural melatonin production decreases as we age, it is (unfortunately) possible that younger women wouldn't see the same benefits as the >56 year-old subjects of the study at hand.

No, I am not recommending laziness here, and I doubt that you will arrive at a cover model physique with nothing but a handful of melatonin pills, but the results of a recent study from the Aarhus University Hospital in Denmark are too intriguing not to devote a whole waredownloadsoft article to them.

In said study, Anne Kristine Amstrup and colleagues tested whether there's anything to the rumors that have it that "melatonin [has] a positive effect on body weight and energy metabolism" (Amstrup. 2015). As the researchers rightly point out, previous "evidence for this relies mainly on animal models" (ibid). It was thus about time for someone to "determine the effects of melatonin on body composition, lipid and glucose metabolism in humans" (ibid).
In this case, said human beings were 81 post-menopausal Caucasian women (aged 56-73 years) diagnosed with osteopenia (T-score between -1 and -2.5 in the hip or spine). The Danish scientists randomized the women to receive

• either melatonin, at a dosage of 1 or 3 mg per day, or
• an identically looking placebo nightly (timing matters!)

for a total time-period of 12 months. There were no dietary or exercise interventions, but all study subjects received a daily supplementation of 800mg calcium and 20ug vitamin D3 (which obviously wouldn't affect the results, also because all of the participants had taken Ca + D3 for at least 3 months before the study began). With DXA, ...

"To assess body composition, we used a whole body scan by dual X-ray absorptiometry (DXA, Hologic Inc., Waltham, MA, USA). We performed scans at baseline and after one year of treatment. Assessments included total and subtotal body mass (g), lean mass (g), fat mass (g) and percentages of body fat. We calculated body mass index (BMI) as body weight (kg) divided by height² (in metres)" (Amstrup. 2015).

... and a detailed analysis of the blood of their subjects, the body composition and biochemical analyses were similarly thorough as the randomization protocol which was performed by an external pharmacy (Skanderborg Pharmacy).
Each block consisted of eight individuals. In the blocks, the women were randomly allocated to treatment, i.e. four received placebo, while two received 1mg of melatonin and two received 3mg melatonin.

Figure 1: Changes in body composition (left) and adiponectin (right) in response to 1-3mg of melatonin taken at night over a 12-months period without further exercise or diet intervention (Amstrup. 2015).

This is also why I have little doubt that we can rely on the data in Figure 1 which shows an astonishingly pronounced reduction in fat mass and a borderline-significant increase in lean mass in the melatonin groups, when the subjects on the placebo supplements gained total (and %) body fat and lost lean mass in the same 12-months period.
The one thing I would still like to repeat is what I already mentioned in the caption of the thumbnail to this article: Since the natural melatonin production decreases as we age and menopaus (Okatani. 2000), it is (unfortunately) possible that younger women wouldn't see the same benefits as the >56 year-old subjects of the study at hand.

Figure 2: Rodent studies also show that melatonin supplementation prolongs the lifespan of the average mouse (Pierpaoli. 1994) and rat (see data in graph) significantly (Oaknin-Bendahan. 1995).

In a similar vein, it cannot be said with any certainty, whether men will benefit to the same extent as the post-menopausal women in the study at hand. While studies in rodents clearly suggest that melatonin works its weight reducing, life pro-longing (see Figure 2) in both male and female middle-aged rodents (Rasmussen. 1999; Wolden-Hanson. 2000), as well as rats who are fed an obesogenic diet like the standard American diet (Prunet-Marcassus. 2003), men are no little mice... but I guess you know that ;-)
References:

• Amstrup, et al. "Reduced fat mass and increased lean mass in response to one year of melatonin treatment in postmenopausal women: A randomized placebo controlled trial." Clinical Endocrinology (2015): Accepted article.
• Leonardo-Mendonça RC,  et al. "The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes." Chronobiol Int. 11 (2015): 1-10. 
• Oaknin-Bendahan, Sol, et al. "Effects of long-term administration of melatonin and a putative antagonist on the ageing rat." Neuroreport 6.5 (1995): 785-788.
• Okatani, Yuji, Nobuyuki Morioka, and Akihiko Wakatsuki. "Changes in nocturnal melatonin secretion in perimenopausal women: correlation with endogenous estrogen concentrations." Journal of pineal research 28.2 (2000): 111-118.
• Prunet-Marcassus, Benedicte, et al. "Melatonin reduces body weight gain in Sprague Dawley rats with diet-induced obesity." Endocrinology 144.12 (2003): 5347-5352.
• Rasmussen, Dennis D., et al. "Daily melatonin administration at middle age suppresses male rate visceral fat, plasma leptin, and plasma insulin to youthful levels." Endocrinology 140.2 (1999): 1009-1012.
• Wolden-Hanson, T., et al. "Daily Melatonin Administration to Middle-Aged Male Rats Suppresses Body Weight, Intraabdominal Adiposity, and Plasma Leptin and Insulin Independent of Food Intake and Total Body Fat 1." Endocrinology 141.2 (2000): 487-497.

Could this large glass of water really be the "diet game changer" some mainstream media make it look like? Or, are we - once again - dealing with the abuse of science to attract readers by propagating dubious dieting myths?

The advice to "drink a glass of water before every meal" is about as old as human efforts to lose weight. Yet despite the fact that an increase in daily water consumption is widely advocated as a useful tool to aid weight loss and even included in popular weight loss programs like Weight Watchers, there is, according to the latest systematic review of the association between water consumption and body weight,  little evidence to support this practice outside of energetically restricted interventions (Muckelbauer. 2013).

In other words: While we do have evidence that replacing caloric beverages with water/diet beverages works (Tate. 2012), we have little evidence that simply drinking more will accelerate weight loss and almost no evidence of the potential benefits water preloading before meals, in particular.
Quite surprising, isn't it. I mean, it should be obvious that drinking a glass or two of water before a meal would be a highly promising strategy to reduce meal energy intake by modifying an individuals’ perception of fullness prior to eating by, as Parretti et al. (2015) put it, "consuming a 'preload' of water". Nevertheless, Daniels' 2010 systematic review identified only two small laboratory studies that specifically investigated whether water preloading reduced energy intake. As Parretti et al. point out in the introduction to their own study,

"[b]oth studies compared participants given a water preload of 500 ml for 30 min before an ad libitum meal with those not given a preload and found that energy intake at the meal was lower for the preload group compared with the no-preload group" (Parretti. 2015). 

Thus, evidence to suggest that water preloading may improve the effectiveness of weight loss programs is there. Experimental evidence to confirm that is yet ultra-scarce. In fact, the only RCT (Dennis. 2015) to directly examine the effects of water preloading before meals on weight loss was published five years ago. In said study, 48 adults with overweight or obesity were allocated to a hypocaloric diet plus 500 ml of water before meals every day (water preload group) or a hypocaloric diet alone intervention (nonwater group) over 12 weeks.

Figure 1: Dennis et al. were the first to show that drinking 500 ml of water before meals everyday can boost the weight loss success of overweight and obese individuals participating a 12-week diet intervention (Dennis. 2010).

As you can see in Figure 1, the subjects in the water group lost ~2kg more weight than their peers and showed a 44% greater decline in weight over the 12 weeks than the nonwater group. That's interesting because the energy intake during test meals was suppressed by the additional water load only at baseline, yet not after 12 weeks on the preloading protocol (see Figure 2).

Figure 1: In a previous study the beneficial effect of the water preload on food energy intake wore off. The subjects in Dennis' study still lost more weight with the preload, but with respect to the long-term efficacy of drinking 500ml of water before every main meal this is an important result we should not forget (Dennis. 2010).

One of the things we will have to look for when analyzing Paretti's more recent study is thus whether she made sure to check if the appetite reducing effects persist. After all, their study was very similar to the one by Dennis, with an important difference in the study population which was not predominantly middle aged or older white men and women in Paretti's study. Otherwise there are only very few surprises with regard to the study design. Here's what we're talking about:

• a two-group randomized controlled trial with eighty-four adults with obesity 
• all participants were given a face-to-face weight management consultation at baseline (30 min) and a follow-up telephone consultation at 2 weeks (10 min)
• participants were randomized to either drinking 500 ml of water 30 min before their main meals or an attention control group where participants were asked to imagine their stomach was full before meals (*)
• primary outcome was weight change at 12-week follow-up

In that, the "(*)" denotes something you might consider weird... and what should I say? It is weird to imagine that your stomach is full before a meal, but that's Parretti's way of turning a regular RCT into an attention controlled RCT, where the dummy procedure disguised the true intent of the study and provided a nonspecific intervention that in some ways matched preloading.

Table 1: Self-reported adherence for both groups - (I) intervention group, (C) control group (Parretti. 2015).

It is thus not really surprising that the subjects in the control group (C) hardly managed to follow the scientists advise once a week, while the majority of the subjects in the intervention group (I) consumed their water preload on at least two of three meals per day. The data in Table 1 does yet still leave no doubt that the adherence declined significantly over the 12-week period. Whether the Parretti study is able to answer the previously raised question, if the chronic use of water preloads may reduce their efficacy, is thus highly questionable. I mean, after 12 weeks, almost half of the subjects didn't use the preload anymore.

Table 2: Self-reported fullness and satiety scores for both groups - (I) intervention group, (C) control group; fullness and satiety scores can range from 1 to 10 (Paretti. 2015)

Against that background, I would not interpret the stable satiety and fullness levels from week 2-9 as evidence that there is no such habituation effect. And in view of the lack of data on the actual food intake, the satiety and fullness data is pretty much irrelevant, anyways (just as there's a disconnect between mTOR and actual muscle gains, there are also disconnects between appetite, fullness and food / energy intake - if you don't measure the relevant outcome you're groping in the dark).

Figure 2: Weight loss (in kg) over the 12-week study period (unadjusted values | Parretti. 2015)

What is relevant and hard to reject, though ,is the fact that the water preloading group lost 1.3 kg more than the subjects in the control group (see Figure 2) - with a statistically significant difference of 1.2 kg still remaining when the data was adjusted for ethnicity, deprivation, age, and gender, the lack of which had been an issue in the previously referenced study by Dennis et al. (2010).
References:

• Daniels, Melissa C., and Barry M. Popkin. "Impact of water intake on energy intake and weight status: a systematic review." Nutrition reviews 68.9 (2010): 505-521.
• Dennis, Elizabeth A., et al. "Water Consumption Increases Weight Loss During a Hypocaloric Diet Intervention in Middle‐aged and Older Adults." Obesity 18.2 (2010): 300-307.
• Muckelbauer, Rebecca, et al. "Association between water consumption and body weight outcomes in children and adolescents: A systematic review." Obesity 22.12 (2014): 2462-2475.
• Parretti, Helen M., et al. "Efficacy of water preloading before main meals as a strategy for weight loss in primary care patients with obesity: RCT." Obesity (2015).
• Tate, Deborah F., et al. "Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial." The American journal of clinical nutrition 95.3 (2012): 555-563.