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. 

Don't get me wrong, the reporting of the aforementioned red meat study was abominable, and the critiques of it that I have had a chance to read have been clear, unequivocal, and spot on (especially this one). 

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

Part I, II

Out of curiosity, using cronometer, I decided to see how much PUFA I was eating on a daily basis for a week.  It was tedious but, on average, I had consumed about 5 grams of PUFA a day, and substantially greater amounts of monounsaturated and saturated fats.  An essential fatty acid (EFA) deficiency is out of the question at this level, at least per the clinicial signs and symptoms, but I naturally began to wonder what my tissues would look like if I had been consuming much less PUFA, essentially depleting myself of linoleic acid (LA) and arachidonic acid (AA). 

It turns out that the synthesis and presence of eicosatrienoic acid (ETA), or mead acid, would increase, in proportion to the exclusion of the EFAs from the diet, and the appearance of ETA can occur in a matter of days.  You’ll seldom find information on ETA in textbooks and in searches on databases that index scientific articles, like PubMed, other than the fact that it serves as a marker for an EFA deficiency.  The mere presence of ETA is also usually taken as evidence that an EFA deficiency has caused, or contributed, to the condition that tends to coexist with it. 

But an EFA deficiency per se is not always at play, as there could be an inability to synthesize and desaturate fatty acids properly, in which case the addition of PUFA would probably provide benefit. (PUFA have indispensable signaling and structural functions, namely in the phospholipids that are found in cell membranes.)  Or, it could merely indicate an overall poor diet.

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