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The "Paleo" cult has repopularized eating and preparing your own (Chicken) bone broth, but will this also help with bone and cartilage health?

Although youre probably thinking of collagen as the stuff thats important for joint health, its implications in human health are more far-reaching than most of us believe.

In fact, collagens are the most abundant group of organic macro-molecules in human and animal body. Because of their tensile strength, they perform numerous structural functions within the body - specifically in connective tissues which include among other tissue also organs as your heart, your intestines, your lungs and the parenchymal organs like the liver and the kidneys and even the fibrous matrix of skin and blood vessels.

As I already said, collagens are yet by far best known as structural components of the protein matrix of the skeleton and its related structures, like bones, teeth, tendons, cartilage and ligament, which bring us back to the original question that bothered me after assuring Chris who emailed me asking about the necessity of taking glycine and proline supplements in the absence of any other protein (my answer was "thats bullocks"): Do glycine and problem supplements even help with collagen synthesis and joint health? Or is the supplement vendor next door the only person who benefits?
We do have evidence (from rodent studies) that the ingestion of low molecular weight (=small peptides) collagen hydrolysates with intact glycyl-prolyl-hydroxyproline tripeptides that actually make it through the gut into the bloodstream and will increasee the organic substance content and decreased the water content of the left femur (Watanabe-Kamiyama. 2009). Previous studies had already shown hat the content of an orally administered gelatin hydrolysate will be incorporated into the cartilage tissue of rats (Oesser. 1999). Similar observations have been made by Iwai et al. for human volunteers and porcine gelatine hydrolysate, as well.

"After the oral ingestion, the peptide form of Hyp significantly increased and reached a maximum level (20-60 nmol/mL of plasma) after 1-2 h and then decreased to half of the maximum level at 4 h after the ingestion. Major constituents of food-derived collagen peptides in human serum and plasma were identified as Pro-Hyp. In addition, small but significant amounts of Ala-Hyp, Ala-Hyp-Gly, ProHyp-Gly, Leu-Hyp, Ile-Hyp, and Phe-Hyp were contained." (Iawai. 2005)

If we assume a similar physiological effect as it was observed by Watanabe-Kamiyama in rodents, the ingestion of (large) quantities of gelatine could thus very well, after its hydrolysation in the gut, have similar effects on human cartilage tissue as the collagen hydrolysate that was used in the Watanabe-Kamiyama study.

Table 1: Summary of Structure and Recovery of Food-Derived Collagen Peptide in Human Serum or Plasma after Oral Ingestion of Gelatin Hydrolysates (Iawai. 2005).

With respect to the occurence of glycyl-polyl-hydroxproline tripeptides, of which the Watanabe-Kamiyama study suggests that they may be responsible for the beneficial effects on cartilage synthesis it should yet be said that it occurred in human plasma only after the ingestion of chicken, but not in porcine collagen in the Iawai study (see Table 1). If thats no coincidence, HARIBO, which is usually made with porcine gelatine is no "collagen builder", a real chicken soup, cooked with bone, on the other hand, could be.

Given that your stomach is working properly a nice paleo bone broth (preferably from chicken bone) could thus produce similar results as a collagen hydrolysate of which a recent review in Current Medical Research and Opinion says that its ingestion stimulates a statistically significant increase in synthesis of extracellular matrix macromolecules by chondrocytes.

Figure 1: Physician rated (top) and subject-rated (bottom) improvement in joint pain walking (left) and standing (right) in the Clark study (Clark. 2008).

The authors, researchers from the University of Illinois College of Medicine at Chicago and the University of Kiel in Germany add:

"These findings suggest mechanisms that might help patients affected by joint disorders such as OA. Four open-label and three double-blind studies were identified and reviewed; although many of these studies did not provide key information – such as the statistical significance of the findings – they showed collagen hydrolysate to be safe and to provide improvement in some measures of pain and function in some men and women with OA or other arthritic conditions." (Bello. 2006)

Subsequent studies such as Benito-Ruiz et al. (2009) or Clark et al. who evaluated data from 97 athletes from a varsity team or a club sport in Pennsylvania support Bellos conclusion (see Figure 1).

Similar beneficial effects were also observed by  et al. in a more recent study with "normal" subjects with articular pain in response to 1,200mg/day of collagen hydrolysate (Bruyère. 2012). When were looking into the effects of single amino acids, however, things look different. If theyre ingested separately, glycine and proline are not going to form a tripeptide in the course of the digestive process. And while they may still serve as a raw material for the endogenous synthesis of such peptides the chance that they actively promote the synthesis of new collagen is slim.
References:

• Bello, Alfonso E., and Steffen Oesser. "Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: a review of the literature." Current Medical Research and Opinion® 22.11 (2006): 2221-2232.
• Benito-Ruiz, P., et al. "A randomized controlled trial on the efficacy and safety of a food ingredient, collagen hydrolysate, for improving joint comfort." International journal of food sciences and nutrition 60.S2 (2009): 99-113. 
• Bruyère, Olivier, et al. "Effect of collagen hydrolysate in articular pain: a 6-month randomized, double-blind, placebo controlled study." Complementary therapies in medicine 20.3 (2012): 124-130.
• Iwai, Koji, et al. "Identification of food-derived collagen peptides in human blood after oral ingestion of gelatin hydrolysates." Journal of agricultural and food chemistry 53.16 (2005): 6531-6536.
• Oesser, Steffen, et al. "Oral administration of 14C labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL)." The Journal of nutrition 129.10 (1999): 1891-1895. 
• Ross, B. D., R. Hems, and H. A. Krebs. "The rate of gluconeogenesis from various precursors in the perfused rat liver." Biochem. J 102 (1967): 942-951.
• Saito, Masataka, et al. "Effect of collagen hydrolysates from salmon and trout skins on the lipid profile in rats." Journal of agricultural and food chemistry 57.21 (2009): 10477-10482.
• Watanabe-Kamiyama, Mari, et al. "Absorption and effectiveness of orally administered low molecular weight collagen hydrolysate in rats." Journal of agricultural and food chemistry 58.2 (2009): 835-841.

Are you training for nothing, if you are "too old" (whatever that may be)? Find out in todays SuppVersity Article!

"The older we get, the weaker we are." Thats something most normal men accept as a given truth - according to the latest science, it does yet appear as if it was more of a self-fulfilling prophecy.

Researchers from the Department of Biology of Physical Activity and Neuromuscular research Center at the University of Jyväskylä in Finland have recently conducted a study to verify the common sense assumption that older men are having a much harder time to to maintain / increase their muscle strength than young ones.

To find out, whether this would also be true for those, who are willing to succumb to a high volume, medium load “hypertrophic” resistance training, the Häkkinen et al. recruited young (28 ± 5 yr, 179 ± 6 cm, 77 ± 12 kg, 21 ± 8 percent fat) and older (65 ± 4 yr, 177 ± 6 cm, 80 ± 10 kg, 23 ± 6 percent fat) men via an advertisement in a local newspaper.
The experimental groups consisted of 23 young and 26 older men (training groups) and the non training control groups consisted of 10 young and 11 older men. The goal was to achieve maximum strength, muscle mass and muscle activation of the lower limbs in both groups.

Table 1:  Resistance training program of the young and older experimental groups (performed with resistance machines)

To this ends, both groups performed 10 weeks of whole-body resistance training twice per week with the emphasis on lower limb exercises. The training program consisted of high volume, medium intensity exercise with short inter-set rest intervals, as it is typically performed by bodybuilders (i.e. 2-5 sets of 8-14 repetitions, 1-2 min rest).

Lower limb exercises, i.e. leg press, knee extension and knee flexion, were performed before upper body exercises. At least 48 h rest was required between training sessions. Maximum dynamic and isometric neuromuscular performance, as well as lean leg and muscle mass were examined before and after the training period. The changes in body composition were assessed 3-4 d and neuromuscular measurements were performed 7 d after the last training session.

Before participating in the study at hand, the "subjects were physically active but unaccustomed to resistance training for the previous 6 months." Training and testing took place throughout the day (9am-7pm), but young and older subjects were pair-matched to avoid any time-of-day effects on neuromuscular performance measurements. All subjects were given nutritional advice in an attempt to maximize muscle hypertrophy, however, no direct nutritional intervention was performed in the present study.
The resistance training program consisted of . Briefly, leg exercises (bilateral leg press, knee extension, and knee flexion) were performad before upper body and torso exercises; bench press, pulldown, shoulder press, seated row, triceps pushdown, biceps curl, abdominal crunches and back raises.

"The subjects performed medium intensity, high volume training consisting of 2–3 sets and 12–14 reps (60–70% 1RM) per exercise (weeks 1–4), then 2–3 sets and 10–12 reps (70–80% 1RM) per exercise (weeks 5–7), and 3–4 sets per exercise and 8–10 reps (75–85% 1RM) per exercise (weeks 8–10). One min rest was given between sets during weeks 1–4, and then 2 min rest was given between sets during the remaining weeks 5–10. One set was performed to failure during each training session." (Häkinnen. 2014)

As youve probably recognized by now this is a more or less classic linear periodization; a very conservative periodization technique with a lot of back up that it works (learn more about periodization).

Figure 1: Pre- and post values for 1RM and isometric leg strength (Häkkinen. 2014)

If you look at the results, youll see that this protocol led to significant increases in one repetition maximum (1RM) leg press performance in both training groups (young: 13 ± 7 %, P < 0.001; older: 14 ± 9 %, P < 0.001).

Interestingly, said performance improvements were accompanied by increased muscle activation, assessed by voluntary activation level (29 ± 51%, P < 0.05) and electromyography amplitude (35 ± 51 %, P < 0.01) in older men only. Unfortunately, only the young men showed significantly increased lower limb lean mass (2.4 ± 2.5 %, P < 0.01), which were furthermore significantly related to the strength increments (r = 0.524, P = 0.01, n = 23).
References:

• Häkinnen, et al. "Similar increases in strength after short-term resistance training due to different neuromuscular adaptations in young and older men." Journal of Strength and Conditioning Research (2014). Publish Ahead of Print.

Even Arnold benefited from ?-hydroxy-isocaproic acid aka HICA - the HICA his body produced and the HICA he got from his diet, whenever he ate cheese and other fermented foods.

You know that I am not the kind of person who likes to tell others what to do. After reading my summary of the contemporary research on ?-hydroxy-isocaproic acid aka HICA, you should yet be able to decide whether its worth a try or not.

If you take a look at the pertinent databases you will realize that there are more patents than papers on ?-hydroxy-isocaproic acid - usually, this is a good indicator we are dealing with another industry scam, but in contrast to the many funky forms of creatine, ?-hydroxy-isocaproic acid does actually have a handful of studies to back up that it does... or I should say "that it could" help you getting big and buffed.
That being said, it may be worth taking a look at what ?-hydroxy-isocaproic acid actually is. Just like HMB which is about to make a comeback in liquid form, these days, HICA is a metabolite of the mTOR and thus protein synthesis triggering branch-chained amino acid leucine. It is also known as "leucic acid" or "DL-2-hydroxy-4-methylvaleric acid" and is formed by ?-hydroxylaction from leucine. Its one of the end-products of leucine metabolism in muscle and connective tissue (Walser. 1978). Its usual concentration in our blood is about 0.2560.02 mmol/L - thats ~100x less than the amount of ?-keto-isocaproic acid (KIC), the corresponding keto acid of leucine of which youll find more than 21 mmol per liter in your blood.

Figure 1: Relative changes in lean mass (%) during 4 weeks of intense soccer training on 1.5g/day HICA (Mero. 2010)

Cheese, wine, soy sauce, etc. - the recently celebrated fermented foods, they all contain HICA, which appears to be the anti-catabolic counterpart to leucine. While the latter is a potent promoter of protein synthesis, the former appears to make sure that the work of its predecessor leucine is not lost.

It is thus no wonder that the promising results of a 2010 study by Mero et al. were recorded during an intensive and thus potentially catabolic training period in soccer athletes. In contrast to the placebo group, where only one individual gained a significant amount of lean mass, while 4 lost muscle, the subjects who had been consuming 1.5g/day of ?-hydroxy-isocaproic acid gained 300g of lean mass, on average, in the course of the 4-week study.

Thats not much and it was not fat free (ca. 150g of fat), but the data in Figure 1 shows that this is a difference between minimal muscle loss and gain... and I guess most athletes would prefer a marginal muscle gain over a marginal loss of lean mass.

HICA, a potent anti-catabolic? I dont think so!

The notion that HICA is, above all, a muscle loss inhibitor appears questionable, if we take a look at the results Charles H. Lang, Hugues Magne, Elizabeth Offord and Denis Breuille presented at a 2013 FASEB meeting. In the abstract to their presentation they cite the results of a rodent study in the course of which the rodents were immobilized for two full weeks. The consequence, an increase in the expression of catabolic hormones and a profound loss of muscle mass was identical in both the HICA and placebo supplemented groups, but in spite of the fact that "?HICA did not alter the immobilization-induced increase in proteasome activity and atrogene expression", the muscle mass had returned to control values only in ?HICA-fed rats after 14 days.
The fast recovery in the HICA group was associated with increased muscle protein synthesis and higher levels of the "protein synthesis pump initiator proteins" S6K1 and 4EBP1 in the previously immobilized muscle. The results Lang et. al. have not yet published in a full paper (at least I couldnt find it) put a huge questionmark behind the long-heralded hypothesis that HICA supplementation would slow muscle loss and puts it in line with its cousin HMB and its precursor leucine as a purported pro-anabolic muscle builder.

Figure 2: Gastrocnemius weight (rel. to control) immediately before and 14-days after the immobilization (Lang. 2013).

The data from the corresponding full paper the authors published a couple of month later in the American Journal of Physiology - Endocrinology and Metabolism you see in Figure 2 are even more impressive, though. According to this rodent data HICA is a more potent muscle (re-)builder than leucine; and, importantly, neither of the two does what the industry keeps promising: prevent muscle catabolism in response to disuse.
Reference:

• Chow K., and Walser M. "Effects of substitution of methionine, leucine, phenylalanine, or valine by their alpha-hydroxy analogs in the diet of rats." J Nutr 1975;105(3):372 8
• Lang, Charles H., et al. "Chronic ?-hydroxyisocaproic acid treatment improves muscle recovery after immobilization-induced atrophy." American Journal of Physiology-Endocrinology and Metabolism 305.3 (2013): E416-E428.
• Mero, Antti A., et al. "Effects of alfa-hydroxy-isocaproic acid on body composition, DOMS and performance in athletes." Journal of the International Society of Sports Nutrition 7.1 (2010): 1.
• Walser, Mackenzie. "Therapeutic compositions comprising alpha-hydroxy analogs of essential amino acids and their administration to humans for promotion of protein synthesis and suppression of urea formation." U.S. Patent No. 4,100,160. 11 Jul. 1978.
• Woods M., and Goldman P. "Replacement of L-Phenylalanine and Leucine by a-Hydroxy analogues in the diets of germ-free rats." J Nutr 1979;709:738 43.

Even if animal fats were the best frying fats, this wouldnt turn  doughnuts into "health food" and french fries into raw carrot sticks.

If you "liked" the SuppVersity on Facebook (www.facebook.com/SuppVersity) you will probably already have seen the controversies and questions my post "Scientists on the Quest for the Perfect Frying Oil" (read more) has triggered. Eventually, it all revolves about yet another of those nutritional wisdoms thats circulating on the Internet: "Ghee, tallow, lard, ... saturated animal fats and the coconut micacle, of course, are the best and only frying oils you should use." (next best Internet source)

How on earth could F. Aladedunye, and R. Przybylski, the authors of the previously cited study even dare stating that high-oleic low-linolenic rapeseed, high-oleic sunflower oils are good frying oils?

But enough of the sarcasm: In todays installment of "True or False" (read previous installments) we will focus solely on the cholesterol-containing animal fats, and save the one and only "coconut miracle" (Coconut oil - virgin, of course - must be good for everything, right? There have after all (E)-Books been written about it ;-) for another installment of this series. So, where do we start then? I guess, we could start by rendering down a big packet of butter in my frying pan... but *wtf* whats that? Its turning tar black!? Can that really be the ideal frying fat? Probably not, but if regular butter sucks, what about clarified butter aka "ghee", then? Its easier to process and there are not tarry clouds floating in the pan, when you heat it.

"But dont we all know that cholestrol aint bad for us?"

Unfortunately, there are other problems with ghee;  problems that are related to the heat-induced oxidation of cholesterol and the presence of large amounts of cholesterol oxides in commercially available "clarified butter" even before you even start heating it as it was reported by Kubow et al. in 1993 (12.3% w/w of total sterols).

If rancid fish full of oxidized PUFA aint bad for us (read previous article), why would we want to use saturated animal fats for frying then? Please note that the overwhelming evidence says that oxidize PUFAs are bad for you.

Not a problem? We all know the whole cholesterol thing is a hoax that was made up just to put everyone on statins? Well, even if that were the case, the "whole cholesterol thing" is about the effects of intact, not oxidized cholesterol on heart health. The oxidized sterols in your "healthy" clarified butter, on the other hand, dont just make it into the bloodstream (Staprans. 1994 & 2003), they will also be incorporated in various tissues (Vine. 1997) and lead to a rapid (+100%) increase the formation of fatty streak lesions in the aorta of lab animals (Staprans. 2000) and have been linked to the unexplained high risk of atherosclerosis in Indian immigrant populations in the US (Jacobson. 1987) as well as the occurrence and progression of atherosclerosis in general (Leonarduzzi. 2002; Gargiulo. 2011).

As mentioned before, butter is unfortunately, not the only high cholesterol item on the Internets list of "best, because highly saturated, frying oils". Next to butter (215mg of cholesterol / 100g) you will also find lard (95mg of cholesterol / 100mg) or tallow (109mg of cholesterol / 100mg) on these lists.
Needless to say that neither tallow nor lard or any other of these animal fats contain enough antioxidants to protect their cholesterol from being oxidized (Ryan. 1981; Park. 1986a,b).

Figure 1: Even if you believed that cholesterol was bad for you, the ~50% reduction in intact cholesterol that occurs, when you heat tallow at temperatures of 155°C and 190°C should not be a reason to celebrate (Park. 1986a)

Interestingly, Park et al. have been able to show that this process starts at temperatures as low as 135°C (the recommended frying temperature for most products is 160°C+) and does not increase with higher temperatures. For pure cholesterol Osada et al. determined 120°C as the lowest temperature that induces oxidative changes (Osada. 1993).

In 1986, a group of researchers who conducted research for the French government found that 78% of the total cholesterol that was lost (23% of total cholesterol) from beef tallow during deep frying was recovered in form of the four best known forms of oxidized cholesterol, i.e. Triol-, 7a-, 7/3-, and 7-Oxo-cholesterol (Bascoul. 1986).

The latter have been shown to decreases barrier function of cultured endothelial cell monolayers (induce leaky gut; Hennig. 1987) and smooth muscle cells (Zwijsen. 1992).

Aside from their previously mentioned effect on the progression of atherosclerosis and their direct effect no the gut lining and other protective barriers in your body. These cholesterol oxidation products (COPs) have also been shown to promote the growth of colon (Kendall. 1992) and other forms of cancer (Sevanian. 1986; Gabitova. 2014), figure in the development of type II diabetes (Mol. 1997), block the production and blood pressure lowering effects of nitric oxide (Brown. 1999) and have been implicated in the development and progression of Alzheimers disease (AD) and vascular dementia, as well as kidney failure (Sottero. 2009)
And while all the non-enzymatically produced COPs in fried (and other) foods are  "bad guys", the enzymatic conversion of cholesterol in the body (see Figure 2, bottom) can produce compounds of which Otaegui-Arrazola, Menéndez-Carreño, and Ansorena write in their 2010 review that they play important biological role.

Figure 2: Not all oxysterols are created equal. Those your body creates by enzymatic reactions figure in cholesterol homeostasis (Otaegui-Arrazola. 2010)

In fact, certain oxysterols can suppress the activation of the master transcriptional regulators of lipid homeostasis (SREBPs) by binding to an oxysterol sensing protein in the Endoplasmic Reticulum, while others accelerate the degradation of the key cholesterol biosynthetic enzyme, HMG-CoA reductase, and/or serve as natural ligand activators of a nuclear receptor (LXR) involved in coordinating many aspects of reverse cholesterol transport (Gill. 2008).

These "good oxysterols" do thus appear(!) to play a subtle but important role in the control of cholesterol homeostasis. In the context of this true or false question, their existence, functions and benefits are however irrelevant. Apropos, question! Whats the answer to our question, after all?
Reference:

• Al-Saghir, Sabri, et al. "Effects of different cooking procedures on lipid quality and cholesterol oxidation of farmed salmon fish (Salmo salar)." Journal of Agricultural and Food Chemistry 52.16 (2004): 5290-5296. 
• Alexander, Charles M., et al. "NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older." Diabetes 52.5 (2003): 1210-1214.
• Bascoul, J., et al. "Autoxidation of cholesterol in tallows heated under deep frying conditions: evaluation of oxysterols by GLC and TLC-FID." Lipids 21.6 (1986): 383-387. 
• Brown, Andrew J., and Wendy Jessup. "Oxysterols and atherosclerosis." Atherosclerosis 142.1 (1999): 1-28.
• Gabitova, Linara, Andrey Gorin, and Igor Astsaturov. "Molecular Pathways: Sterols and receptor signaling in cancer." Clinical Cancer Research 20.1 (2014): 28-34.
• Gargiulo, Simona, et al. "Plaque oxysterols induce unbalanced up-regulation of matrix metalloproteinase-9 in macrophagic cells through redox-sensitive signaling pathways: Implications regarding the vulnerability of atherosclerotic lesions." Free Radical Biology and Medicine 51.4 (2011): 844-855.
• Gill, Saloni, Renee Chow, and Andrew J. Brown. "Sterol regulators of cholesterol homeostasis and beyond: the oxysterol hypothesis revisited and revised." Progress in lipid research 47.6 (2008): 391-404. 
• Gupta, R., and V. P. Gupta. "Meta-analysis of coronary heart disease prevalence in India." Indian heart journal 48.3 (1995): 241-245.
• Hennig, Bernhard, and Gilbert A. Boissonneault. "Cholestan-3gb, 5?, 6?-triol decreases barrier function of cultured endothelial cell monolayers." Atherosclerosis 68.3 (1987): 255-261.
• Jacobson, MarcS. "Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations." The Lancet 330.8560 (1987): 656-658. 
• Kendall, Cyril W., et al. "Effect of dietary oxidized cholesterol on azoxymethane-induced colonic preneoplasia in mice." Cancer letters 66.3 (1992): 241-248.
• Kubow, Stan. "Lipid oxidation products in food and atherogenesis." Nutrition reviews 51.2 (1993): 33-40.
• Leonarduzzi, Gabriella, Barbara Sottero, and Giuseppe Poli. "Oxidized products of cholesterol: dietary and metabolic origin, and proatherosclerotic effects (review)." The Journal of nutritional biochemistry 13.12 (2002): 700-710.
• Mol, Marc JTM, et al. "Plasma levels of lipid and cholesterol oxidation products and cytokines in diabetes mellitus and cigarette smoking: effects of vitamin E treatment." Atherosclerosis 129.2 (1997): 169-176. 
• Osada, Kyoichi, et al. "Oxidation of cholesterol by heating." Journal of Agricultural and Food Chemistry 41.8 (1993): 1198-1202. 
• Otaegui-Arrazola, A., et al. "Oxysterols: a world to explore." Food and Chemical Toxicology 48.12 (2010): 3289-3303.
• Park, S. Won, and Paul B. Addis. "Identification and quantitative estimation of oxidized cholesterol derivatives in heated tallow." Journal of agricultural and food chemistry 34.4 (1986a): 653-659. 
• Park, S., and P. B. Addis. "Further investigation of oxidized cholesterol derivatives in heated fats." Journal of Food Science 51.5 (1986b): 1380-1381.
• Pie, Jae Eun, Khira Spahis, and Christine Seillan. "Cholesterol oxidation in meat products during cooking and frozen storage." Journal of agricultural and food chemistry 39.2 (1991): 250-254.
• Ryan, Thomas C., J. Ian Gray, and Tan D. Morton. "Oxidation of cholesterol in heated tallow." Journal of the Science of Food and Agriculture 32.3 (1981): 305-308. 
• Sottero, Barbara, et al. "Cholesterol oxidation products and disease: an emerging topic of interest in medicinal chemistry." Current medicinal chemistry 16.6 (2009): 685-705.
• Sevanian, A., and A. R. Peterson. "The cytotoxic and mutagenic properties of cholesterol oxidation products." Food and Chemical Toxicology 24.10 (1986): 1103-1110.
• Staprans, Ilona, et al. "Oxidized lipids in the diet are a source of oxidized lipid in chylomicrons of human serum." Arteriosclerosis, Thrombosis, and Vascular Biology 14.12 (1994): 1900-1905. 
• Staprans, Ilona, et al. "Oxidized cholesterol in the diet accelerates the development of atherosclerosis in LDL receptor–and apolipoprotein E–deficient mice." Arteriosclerosis, thrombosis, and vascular biology 20.3 (2000): 708-714.
• Staprans, Ilona, et al. "Oxidized cholesterol in the diet is a source of oxidized lipoproteins in human serum." Journal of lipid research 44.4 (2003): 705-715.
• Tsai, Lee Shin, and Carol A. Hudson. "Cholesterol oxides in commercial dry egg products: quantitation." Journal of Food Science 50.1 (1985): 229-231.
• Vine, D. F., et al. "Absorption of dietary cholesterol oxidation products and incorporation into rat lymph chylomicrons." Lipids 32.8 (1997): 887-893.
• Zwijsen, Renate ML, Ingeborg MJ Oudenhoven, and Laura HJ de Haan. "Effects of cholesterol and oxysterols on gap junctional communication between human smooth muscle cells." European Journal of Pharmacology: Environmental Toxicology and Pharmacology 228.2 (1992): 115-120.

Nicotine gums are made for smokers. Smokers are leaner than no-smokers. Chewing nicotine gums helps you lean out... broscience? Logic? Or bullshit?

Its one of the better-known pieces of broscience: "Nicotine chewing gums will promote weight loss!" Aside from being "better-known", its yet also highly controversial. In that, people usually dont question the fact that nicotine chewing gums may promote weight loss (we do all know that smokers, are leaner, dont we?), but rather that they do so in the absence of significant ill-health effects.

Since this is the SuppVersity and not the bb.com bulletin board, I am not going to restrict todays analysis on the health issues. Instead, I will start by looking for scientific evidence that would confirm the common sense assumption that chewing nicotine gums does in fact promote weight loss -- in humans, not in rodents (Lupien. 1988).
Lets first take a look at the connection between nicotine and body weight management in general. In 2006 Chen et al. published an intriguing paper the title of which could in fact explain why smokers tend to be lighter than non-smokers (for US citizens thats ~ 3.7% leaner; cf. Albanes. 1987): "Cigarette Smoke Exposure Reprograms the Hypothalamic Neuropeptide Y Axis to Promote Weight Loss" (Chen. 2006)

According to Chen et al., the anorexic effects they observed in a 4 week rodent study are behind the anti-obesity effects of smoking. Similar effects on appetite in general and reductions in sugar cravings (Grunberg. 1982) in human studies as well. Nevertheless, if a reduction in appetite was the only beneficial effect of nicotine would be limited to phases of ad-libitum dieting. A direct effect on fat loss, as it is implied by broscience, on the other hand, would not exist.
If it was not for Schechter et al. and other scientists who report "nicotine-induced weight loss in rats without an effect on appetite" (Schechter. 1976), I could stop here and tell you that (a) you obviously dont want to chew nicotine gums for the rest of your life to benefit from its appetite suppressing phases and that (b) it wouldnt make sense to chew them in a phase, where youre counting calories, anyway (if you want the appetite suppressing effects, anyway, add caffeine, this will enhance them; Jessen. 2005).

Figure 1: Body weight and food intake in 13 week rodent study with 0.4mg/kg and 0.8mg/kg (right) of nicotine administered in solution or saline control thrice daily (Schechter. 1976)

Thanks to the impressive reduction in body weight Schlechter et al. observed in the previously cited rodent study in the absence of statistically significant reductions in food intake (graphs at the bottom of Figure 1), its worth to keep digging further.
If you take a close look at the results you will yet realize that there is a big caveat to the impressive weight loss (specifically in the 3x0.8mg/kg group | human equivalent ~ 3x4mg or three high dose nicotine chewing gums). Yes, I am talking about the the nasty weight regain that occurred - likewise in the absence of increased food intakes - when the nicotine administration was seized.

Against that background, its all the more important to find evidence from human studies. Unfortunately, the majority of studies on nicotine gums is not relevant to the topic, because they are (a) dealing with the success of smoking cessations, or (b) dealing with weight regain after smoking cessation. We will therefore have to resort to ostensibly unrelated results such as...

• Figure 3: Plasma leptin levels in non-smokers, long-term nicotine gum users and smokers after adjustment for age and body composition (Eliasson. 1999)

  the increase in leptin levels researchers from the Sahlgrenska University Hospital in Göteborg (Sweden) observed in a 1999 study in 73 subjects: 23 non-smokers, 31 smokers and 19 long-term nicotine gum chewers (NGCs) with similar ranges of age, body mass index (BMI) and per cent body fat. As the authors of the corresponing paper point out, "[t]he increased leptin levels may be an important reason for the lower body weight in smokers." (Eliasson. 1999). Unfortunately "long-term" is nothing you would associate with the use of nicotine gums as diet adjuvant.
  
  As suggestive as they may be, the increases in leptin are thus probably not relevant for short term decreases in body weight - or even better body fat - as you would expect them, when youre dieting.
• the association with hyperinsulinemia and insulin resistance the same Swedish researchers from the Sahlgrenska University Hospital observed in a previous investigation (Taskinen. 1996) clearly suggest that the chronic consumption of nicotine leads to insulin resistance, metabolic abnormalities associated with the insulin resistance syndrome, and increased cardiovascular morbidity.
  
  On the other hand, we are - I cant repeat that often enough - not talking about the chronic use of nicotine gums, but their (ab-)use for 4-6 weeks to propel your fat loss results. Eventually, the results are thus as irrelevant as the previously mentioned beneficial effects on leptin (see previous bullet-point).

• Figure 4: Thermogenic effect in 150min after the ingestion of nicotine and / or caffeine (Jessen. 2003)

  the "pronounced" thermogenic effect researchers from the The Royal Veterinary and Agricultural University in Denmark observed in their 2003 study. Aside from scientific evidence that the administration of nicotine has thermogenic effects, the second important result of the study at hand is the observation hat the thermogenic effects  of 1 mg nicotine (measured over 150 min after the ingestion) can be (almost) doubled, if the nicotine is administered in conjunction with 100 mg of caffeine (Jessen. 2004).
  
  Its also important to note that "[i]ncreasing the nicotine dose to 2 mg does not increase the thermogenic effect but produces side effects in most subjects." (Jessen. 2003) More is thus, as so often, not better for nicotine (a similar non-linear dose-response effect was observed with cigarettes, as well; cf. Collins. 1996). A previous study by Collinset al. (1994) found a 7.5% increase in resting energy expenditure with 200mg of caffeine and a similarly low amount of nicotine, i.e. 0.8mg of nicotine from cigarette smoke over a 3h period.

If you take a look at the evidence I provided, it supports the previously raised concerns about the long-term use of nicotine gums. On the other hand, the study by Jessen et al., as well as the study Collins et al. who didnt just find a similar synergistic effect of caffeine and nicotine, but were also able to show that the effects occur in both smokers and non-smokers (Collins. 1994; similar results in Perkins. 1989), clearly indicate that the short-term (ab-)use of nicotine gums may in fact promote the loss of body weight and - assuming youre getting your 1.5g/kg protein and lifting heavy objects - body fat, as well.
Unfortunately, it is difficult to say whether these benefits come with significant negative effects on your health. Evidence on short-term effects of nicotine abuse in human beings is scarce. Furthermore studies in non-smokers suggest that healthy people and people with pre-existing problems with glucose management react differently, with the former experiencing no and the latter experiencing severe reductions in insulin resistance in response to the acute infusion of nicotine in a 2001 study by Axelsson et al.

Figure 6: Negative effects of nicotine on insulin sensitivity occur only in diabetics (Axelsson. 2001)

As far as the dreaded increases in insulin resistance are concerned, you could thus argue that the contemporary evidence suggest that healthy athletic individuals have nothing to fear. Since the same appears to be true for the negative effects on platelet count (Mundal. 1995), blood pressure and other markers of cardiovascular health (Benowitz. 2002). For people who belong to one of the classic risk groups, i.e. men and women with metabolic syndrome and / or existing heart condition, the use of nicotine gum may yet easily result in a hospital stay or worse (Rigotti. 1986).
References:

• Albanes, Demetrius, et al. "Associations between smoking and body weight in the US population: analysis of NHANES II." American Journal of Public Health 77.4 (1987): 439-444.
• Axelsson, T., et al. "Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects." Journal of internal medicine 249.6 (2001): 539-544.
• Benowitz, Neal L., Anna Hansson, and Peyton Jacob. "Cardiovascular effects of nasal and transdermal nicotine and cigarette smoking." Hypertension 39.6 (2002): 1107-1112.
• Chen, Hui, et al. "Cigarette smoke exposure reprograms the hypothalamic neuropeptide Y axis to promote weight loss." American journal of respiratory and critical care medicine 173.11 (2006): 1248-1254.
• Collins, L. C., et al. "Effect of caffeine and/or cigarette smoking on resting energy expenditure." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 18.8 (1994): 551-556. 
• Collins, Lynell C., Jerome Walker, and Bryant A. Stamford. "Smoking multiple high-versus low-nicotine cigarettes: impact on resting energy expenditure." Metabolism 45.8 (1996): 923-926.
• Dallongeville, Jean, et al. "Cigarette smoking is associated with unhealthy patterns of nutrient intake: a meta-analysis." The Journal of nutrition 128.9 (1998): 1450-1457.
• Eliasson, Björn, and Ulf Smith. "Leptin levels in smokers and long?term users of nicotine gum." European journal of clinical investigation 29.2 (1999): 145-152. 
• Etter, Jean-François. "Addiction to the nicotine gum in never smokers." BMC public health 7.1 (2007): 159.
• Grunberg, Neil E., Deborah J. Bowen, and Suzan E. Winders. "Effects of nicotine on body weight and food consumption in female rats." Psychopharmacology 90.1 (1986): 101-105.
• Grunberg, Neil E. "The effects of nicotine and cigarette smoking on food consumption and taste preferences." Addictive behaviors 7.4 (1982): 317-331.
• Grunberg, N. E., S. E. Winders, and K. A. Popp. "Sex differences in nicotines effects on consummatory behavior and body weight in rats." Psychopharmacology 91.2 (1987): 221-225.
• Jessen, Anna B., Søren Toubro, and Arne Astrup. "Effect of chewing gum containing nicotine and caffeine on energy expenditure and substrate utilization in men." The American journal of clinical nutrition 77.6 (2003): 1442-1447.
• Jessen, A., et al. "The appetite?suppressant effect of nicotine is enhanced by caffeine*." Diabetes, Obesity and Metabolism 7.4 (2005): 327-333. 
• Mundal, H. H., K. Gjesdal, and P. Hjemdahl. "Acute effects of low dose nicotine gum on platelet function in non-smoking hypertensive and normotensive men." European journal of clinical pharmacology 47.5 (1995): 411-416. 
• Lupien, John R., and George A. Bray. "Nicotine increases thermogenesis in brown adipose tissue in rats." Pharmacology Biochemistry and Behavior 29.1 (1988): 33-37.
• Perkins, Kenneth A., et al. "Metabolic effects of nicotine in smokers and non-smokers." Problems of Drug Dependence 1989 (1989): 469.
• Perkins, Kenneth A., Joan E. Sexton, and Amy DiMarco. "Acute thermogenic effects of nicotine and alcohol in healthy male and female smokers." Physiology & behavior 60.1 (1996): 305-309.
• Rigotti, Nancy A., and Kim A. Eagle. "Atrial fibrillation while chewing nicotine gum." Jama 255.8 (1986): 1018-1018.
• Schechter, Martin D., and Peter G. Cook. "Nicotine-induced weight loss in rats without an effect on appetite." European journal of pharmacology 38.1 (1976): 63-69.
• Taskinen, Marja-Riitta, and Ulf Smith. "Long-term use of nicotine gum is associated with hyperinsulinemia and insulin resistance." Circulation 94.5 (1996): 878-881.