New Gundry Book - The Plant Paradox

[circular]

Thx Stavia, should you get interested in HOMA-IR, you can google calculators where all you do is enter fasting glucose and insulin values.

[Tincup]

Thx Stavia, should you get interested in HOMA-IR, you can google calculators where all you do is enter fasting glucose and insulin values.

Circ, the issue is insulin response. Catherine Crofts looked at all the data from Joseph Kraft's ~15,000 five hour oral glucose tolerance tests with insulin assays and tried to determine the next best (and simpler) test. The answer was the 2 hour insulin test. See here I know that when I ate the HCLF vegan diet, my trigs were still in the 50's and HDL in the lower 40's. I just really don't like the relatively low HDL and high Tg. Your hubby is lean, but I have no idea if he is TOFI (thin outside, fat inside), that was my ex till she switched to a much lower carb diet. As I recall, Julie too.

Insulin, glucose, HOMA all look great, but with a family history and the Tg's and HDL's he presents with, I'd want to look more closely.

As you know, I'm not a doc, so just my instinct. If you read Croft's thesis, you'll see that the key is insulin response, not just fasting insulin and glucose.

[circular]

Thank you George! I just read Craft's work you link to. Much clearer now. I'll work on him. I may need to invent the first home insulin meter, at least I've not heard one is available.

[Russ]

W/r to earlier conversations about Neu5gc, picking up on pasted comments from Gundry in the broths and organ meats thread, enabled me to find the source article wherein he referred to this recent 2017 paper which looks pretty good...

"Biochemical, Cellular, Physiological, and Pathological Consequences of Human Loss of N-Glycolylneuraminic Acid"
by Okerblom and Varki
https://www.researchgate.net/publicatio ... minic_Acid

Abstract
About 2-3 million years ago, Alu-mediated deletion of a critical exon in the CMAH gene became fixed in the hominin lineage ancestral to humans, possibly through a stepwise process of selection by pathogen targeting of the CMAH product (the sialic acid Neu5Gc), followed by reproductive isolation via female anti-Neu5Gc antibodies. Loss of CMAH has occurred independently in some other lineages, but is functionally intact in Old World primates, including our closest relatives, the chimpanzees. While the biophysical and biochemical ramifications of losing tens of millions of Neu5Gc hydroxyl groups at most cell surfaces remains poorly understood, there are multi-scale effects functionally relevant to both sides of the host-pathogen interface. Hominin CMAH loss may also contribute to understanding human evolution, at a time where our ancestors were starting stone tool use, increasing their consumption of meat, and possibly hunting. Comparisons with chimpanzees within ethical and practical limitations have revealed some consequences of human CMAH loss, but more has been learned using a mouse model with a human-like Cmah inactivation. For example, such mice can develop antibodies against Neu5Gc that could affect inflammatory processes like cancer progression in the face of Neu5Gc metabolic incorporation from red meats, display a hyper-reactive immune system, a human-like tendency for delayed wound healing, late onset hearing loss, insulin resistance, susceptibility to muscular dystrophy pathologies, and increased sensitivity to multiple human-adapted pathogens involving sialic acids. Further studies in such mice may provide a model for other human-specific processes and pathologies involving sialic acid biology that have yet to be explored.

I managed to get the pull paper from the authors, and paste in...

...2 key paragraphs...

"All humans who have consumed Neu5Gc express variable levels of circulating anti-Neu5Gc antibodies. The antigenicity of humans against Neu5Gc is not inherited from the mother, rather it has been attributed to its cell-surface presentation by common commensal bacteria (e.g. , Haemophilus influenza) after consumption of Neu5Gc after birth,[52,103] potentially coin- ciding with the introduction of cow based infant formula and baby food. Thus, all humans who continue to consume Neu5Gc could experience “xenosialitis”, the host response to a foreign but metabolically tolerated antigen (reviewed exten- sively elsewhere).[54, 55, 58, 189] Briefly, red meat is particularly high in Neu5Gc compared to poultry and fish, which contain low or undetectable Neu5Gc content (with the exception of cavi- ar).[108,190] When Neu5Gc-rich food is consumed, it is absorbed and either eliminated in urine or metabolically incorporated into some tissues.[52,191] The display of this foreign antigen in- duces an immune response through antibody- and comple- ment-mediated xeno-autoantigen immunity. Chronic inflamma- tion induced in this way was recently shown to increase the propensity for carcinoma formation in the Cmahˇ/ˇ mouse.[108]

In this regard, Neu5Gc has been reported for decades as a potential antigen in multiple cancer pathologies including lung,[51] liver,[51, 192] colon,[47, 51, 193] kidney,[194] breast,[50, 52, 195] skin,[195–197] ovary,[197] and throat[198] cancers as well as malignant lymphoma.[51] Although nutritional incorporation alone does not lead to anti-Neu5Gc immunization in Cmahˇ/ˇ mice, anti- Neu5Gc immunization is achieved by co-stimulation through injection with chimpanzee red blood cells (RBCs) or with Neu5Gc-containing tumor cell lines.[103] Cmahˇ/ˇ mouse anti- Neu5Gc antibody production has become an important model for the study of Neu5Gc antigenicity in humans.[54, 55, 58, 189] Anti- Neu5Gc antibodies have been directly shown to enhance tumor growth in Cmahˇ/ˇ mice by promoting cancer-associat- ed inflammation[104,108] and anti-Neu5Gc antibodies have been identified as potential serum biomarkers for tumors in humans.[107] The possibility that higher levels of antibodies might be tumoricidal needs further study, as anti-Neu5Gc pas- sively transferred into mice bearing a syngeneic MC-38 colon adenocarcinoma display a hormetic relationship between tumor growth and antibody dose.[105,106] The potential effects of anti-Neu5Gc antibodies on the vascular endothelium have been modeled in vitro but have yet to be described in vivo.[121] Neu5Gc aggregates have also been found in dystrophic human and Cmahˇ/ˇ mouse muscle tissue,[120] but the implica- tions of this are not yet fully understood."

...the summary/outlook here also...

"Due to the high prevalence of sialic acids on all cell surfaces, the loss of CMAH in the hominin lineage likely had complex physiological ramifications, as evident in the multiple organ and cell types affected in Cmah mice. Many of these phenotyp- ic differences observed between WT and Cmahˇ/ˇ mice are possibly analogous to differences between humans and chim- panzees, but much more work is needed to understand the many mechanisms likely to be at play. Importantly, these mechanisms could have implications for the treatment of dis- eases specifically affecting humans, such as muscular dystro- phy, that are difficult to model in rodents. Exogenously, many deadly human pathogens have a Neu5Ac preference and pos- sibly a linkage-specific preference contributing to their species- specific infectivity, as is the case with influenza. Furthermore, many pathogens, commensal bacteria, and/or symbiotic bacte- ria, such as S. pneumoniae, might have an optimal metabolic preference for Neu5Ac over Neu5Gc. Many of these and other questions about human sialic acid biology remain unexplored or unreported. The hope is that these studies will highlight the great importance of sialic acids and spur further investigations towards the development of therapeutics."

Overall pretty good (as far as I can grasp) as a "state of our current knowledge" paper. They build a good case as to why Neu5gc is likely to have immune system implications, and even postulate on origins of its loss in humans as preferential reduction in affinity for some parasites. Some evidence for potential health implications in mouse knock-outs.

Although I can even imagine that where Dr Gundry has some very specific knowledge here from his work in organ transplant immune response management, I think it is also fair to say that this paper doesn't even try to make a broad claim like "don't eat red meat." I think it remains an interesting subject for research, and (as discussed before) may be particularly relevant to anyone with an autoimmune condition (or possibly even just leaky gut).

But I also think there are some really interesting unexplored angles here which could end up pointing things the other way... e.g. it is very clear that this gene was lost in humans at a time when they were beginning to eat more read meat (and thus also likely associated with the early success of the APOE4 gene as a differential with primates). My conclusion is that it's too early to draw any conclusions, but mark it as a subject worth staying up to date on.

Russ