The interplay among the human intestinal microbial landscape, obesity, metabolism, and nutritional status: an overview

INTRODUCTION 

I’ve been paying much more attention to the human intestinal microbial landscape because of the red meat-carnitine study, and more recently, this one.  There is a growing body of compelling evidence linking the types of bacteria that colonize our intestines, and therefore the types of toxins we are exposed to, and our risk of diseases that include obesity. 

I’ve written about this before, namely with respect to the gram-negative bacterial toxin, lipopolysaccharide (LPS), as it relates to physical attractiveness, as well as the apparent beneficial metabolic effects of sterilizing the intestines of all microbial life.

I don’t want to dwell on this matter, but I do want to try to delve further into the intricacies of the topic and the evidence in which many of the suppositions are based, and towards the end, shed light on some pathways that open up possibilities for intervention.

What I learned from the red meat-carnitine study (plus what I ate today)

The red meat-carnitine study¹ has made the rounds on the interwebz and many a blogger has had an opportunity to thoroughly deconstruct it, and, as usual, the data presented in the study did not, in any way, warrant the sensationalism and conclusion—that the consumption of red meat could lead to heart disease on the basis of its carnitine content—drawn by the press and media. (Though, the distinction that having “healthy” gut flora as opposed to normal or unhealthy would inhibit the conversion of carnitine to TMAO is lost on me.)

It was an easy one to swat down, but what was interesting to me was the fervor and vitriolic, yet laser sharp, scrutiny (and of course, all wrapped up with the obligatory pleas for critical thinking), with which this particular study was jumped on by the Paleo diet community in the defense of their sacred cow: red meat.

The inverse relationship between the quality assessment of a study and confirmation bias is ever present in science, and not necessarily wrong, but members of diet movements tend to take it to a level that ends up making me feel uncomfortable and nauseous.  It's simply human nature to scrutinize studies that tend to disagree with our preconceived beliefs more intensely than those that tend to agree with them, but this bias rears its ugly head so often and so blatantly in the Paleosphere so as to be reprehensible. 

PUFA, lipid peroxidation processes, and the implications for atherosclerosis and diet Part II

Please bear with me for this one, as I want to address a comment that was left on my blog regarding fish, namely how it exerts its beneficial effects.  Apparently, the folks over at PHD believe fish oil is beneficial by way of hormesis, which is the idea that the exposure to small doses of a toxin fortifies our resistance to it upon subsequent exposures.

In the case of fish oil, the previously mentioned decomposition products, derived mainly from DHA and EPA hydroperoxides, are the toxins that elicit hormetic responses.  Toxic in themselves, these lipid hydroperoxides are the starting material for a host of highly toxic decomposition products, including 4-hydroxyhexenal (4-HHE), which is the one that is usually evoked to discuss the potentially beneficial hormetic effect of fish oil.

4-HHE corresponds to 4-hydroxynonenal (4-HNE), which is generated from linoleic acid (LA) and arachidonic acid (AA).  Compared to 4-HNE, there have been fewer studies conducted with respect to the toxicity of 4-HHE.   However, I think it would be reasonable to assume, given their structural similarities, that 4-HNE and 4-HEE would produce similar effects in the body.  (2-hydroxyheptanal, also derived from LA, has similar effects to 4-HNE.)  Regardless, 4-HNE can be, and is probably, produced from EPA and DHA as well.¹

4-HNE is highly reactive and highly toxic, plain and simple.  It’s also physiologically relevant because LA and AA are the major PUFA found in mammalian tissue, especially in phospholipids and lipoproteins.  Aldehydes like these, and their oxidation products, like oxime and pyrazoline, have been found to accumulate in old age,² atherosclerosis, and inflammatory conditions like rheumatoid arthritis.³

PUFA, lipid peroxidation processes, and the implications for atherosclerosis and diet

I recently read on the interwebz that fish oil lowers triglyceride levels in the blood by depositing them in the arteries.  I have known about this triglyceride lowering effect, and whether I should be taking fish oil as a supplement as is recommended by major health organizations, alternative health practitioners, and my mom. 

As a whole, I think the clinical trial evidence for fish oil for the prevention and treatment of cardiovascular disease, especially of late, have been disappointing, to say the least, and this goes for the other conditions for which fish oil has been, for years now, said to benefit.  Fish oil does in reality lower triglycerides but what is the trade-off? 

Studies like this one by Angerer et al., for instance, in which subjects who were randomized to receive fish oil—1.65 grams of omega-3 fatty acids per day— or a placebo demonstrated, after two years, a greater degree of atherosclerosis in the carotid arteries of the subjects who had received fish oil compared to those who had received a placebo.¹

The presence of highly reactive methylene groups renders PUFA highly susceptible to peroxidation processes, and the more double bonds a PUFA molecule has, the greater the chance becomes.  As an example, DHA and EPA are more susceptible than arachidonic acid (AA), which are both more susceptible than linoleic acid (LA) and alpha linolenic acid (ALA) to lipid peroxidation processes.