Monday, August 9, 2021

References for Ancestral Health Symposium 2021 talk, "Why Did We All Get Sick?"

Slide 11:

“Thus, as modern food preparation techniques spread throughout the world during the 19th century, so did dental crowding [malocclusion].” (Rose & Roblee, 2009)

Slide 18:

“Between 1900 and 1920… the death rate from diabetes, despite improved treatment of the disease, had increased by as much as 400 percent... It had increased fifteen-fold since the end of the Civil War.” (Taubes, 2008)

Slide 20:

“Sesame seed first cultivated ~5 Kya, in India, oil extracted by crushing” (Fuller, 2003)

Sesame seed oil spread into Egypt, the Mediterranean, and Africa

Safflower was cultivated in Egypt, use was common in Ptolemaic period, but references begin 3.5 Kya

Used as food and for lamps

Animal fat illegal in Ptolemaic Egypt (!) (Sandy, 1989)

Slide 21

Modern mass-production of seed oils started in 19th century, 200 ya

“By the early 19th century, Russian farmers were growing over 2 million acres of sunflower”

(The National Sunflower Association)

American production was mostly cottonseed oil, first a toxic waste product

Generally the manufacturers in the United States make no pretence [sic] of exporting pure lard….

“The chief adulterant found is cotton seed oil”

(Dominion of Canada, 1890)

Hydrogenated cottonseed oil (Crisco) introduced in 1911, taking vegetable fats mainstream

Slide 22

Cottonseed ruled until soybean oil introduced

Biggest change in diet in modern era is increase in seed oils

(Blasbalg et al., 2011)

Slide 23

“The Nutrition Transition: New Trends in the Global Diet”

“By the 1990s,soybean oil accounted for about 70% of… edible oils and fats in the [US]… soybeans now account for the bulk of vegetable oil consumption worldwide

“This dramatic difference was largely accounted for by a major increase in the consumption of vegetable fats by poor and rich nations alike

“Although meat consumption declined in high-income countries (by 6-9%), there was little overall reduction in fat intakes, as animal fats were replaced by a greater proportion of vegetable oils and products”

(Drewnowski & Popkin, 1997)

Slide 24

“Fifty years later, I still cannot cite a definite mechanism or mediator by which saturated fat is shown to kill people.”

(Lands, 2008)

Slide 27

HNE is involved in every aspect of Chronic Disease

Marker/mediator of Oxidative Stress
(Tsimikas, 2006; Žarković et al., 1999)

Induces

Atherosclerosis (Willeit et al., 2020; Witztum & Steinberg, 1991)

Insulin resistance (Ingram et al., 2012; Pillon et al., 2012)

DNA damage (Chung et al., 2003; Hu et al., 2002)

Inflammation (Poli & Schaur, 2000; Trevisani et al., 2007)

Mitochondrial Dysfunction (Gomes et al., 2014)

Fibrosis (Chiarpotto et al., 2005; Gomes et al., 2014)

Pain (C. Li et al., 2018; Trevisani et al., 2007) (Mis-cited as Trevisani et al., 2017; Chen et al., 2018)

Etc (Poli & Schaur, 2000; Shoeb et al., 2014; Sottero et al., 2019)

HNE is derived exclusively from n-6 fats (Ayala et al., 2014)

Slide 28

“So few subjects in the present survey were found to have any of the conventional signs of coronary disease that it would be futile to analyze the data with any hope of defining the existence of risk factors for this disease within this population. ” (Sinnett & Whyte, 1973b)

Slide 29

Cardiovascular Disease (CVD) is a modern disease

While it existed in Ancient Egypt… (Finch, 2011)

“Heart disease was an uncommon cause of death… at the beginning of the 20th century. By midcentury it had become the commonest cause” (Dalen et al., 2014)

And when heart attack was unknown, some ate lots of animal fat (Michaels, 1966)

CVD is still unknown in populations eating ancestrally—no industrially-produced food (Kaplan et al., 2017)

Slide 30

In the 1960s, researchers looked at CVD in different countries. (Lee et al., 1964)

They used heart attack determined by autopsy, an extremely reliable method

Was CVD genetic, or environmental?

They used thousands of autopsies, even bringing some hearts back to the US to confirm diagnosis

What they found confirms the earlier studies…

Slide 32

So what could the environmental factor be?

In the 1970s, Brown and Goldstein attempted to induce the first step of atherosclerosis (Goldstein et al., 1979)

It failed

LDL would not convert macrophages to foam cells

They discovered the LDL must be modified

Slide 33

Steinberg and Witztum demonstrated the nature of the modification (Witztum & Steinberg, 1991)

Fats in the LDL must be oxidized, when they are sufficently oxidized, foam cells (poisoned macrophages) will form

OxLDL is cytotoxic: toxic to cells.

The toxins in oxLDL are oxidized n-6 fats, such as HNE

Slide 34

Human studies show that dietary seed oils lead to LDL oxidation (Reaven et al., 1993; Witztum & Steinberg, 1991)

Several human RCTs demonstrate higher CVD events with seed oil feeding (Ramsden et al., 2016 Appendix part 2)

One RCT reduced n-6 intake to an evolutionarily-appropriate level, saw a 70% decline in CVD events (de Lorgeril et al., 1994)

“…if you… remove [oxLDL] from "LDL-C" to derive a corrected LDL-C, corrected LDL-C is NO LONGER predictive of events.” (Willeit et al., 2020)

Tsimikas tweet thread.

Slide 36

Chart (Hiraga, 2014)

Slide 38

“The diet consisted almost entirely of sweet potato, carbohydrate providing over 90% of the calories.”

“No clinical evidence of diabetes mellitus was found in this survey.” (Sinnett & Whyte, 1973a, 1973b)

Slide 39

And since you’re wondering… (Lai et al., 2013)

They do eat less sucrose, but compare to Chinese children (Afeiche et al., 2018)

Data in graphs from sources cited above.

Slide 41

Lots of populations ate/eat traditional diets w/out T2DM

“…their mean two-hour post-glucose level of 121 mg/ 100 ml could be regarded as falling within the "diabetic" range.”

“…the relative carbohydrate intolerance of our primitive Bushmen subjects is at first glance rather surprising.” (Joffe et al., 1971)

“…the prolonged increase after two hours in both San series certainly suggested a diabetes-like condition in the San…” (T. Jenkins et al., 1974)

Slide 42

!Kung eat lots of mongongo fruit and nuts

As much as 1/3 of their calories. (Bindon, 2009)

Mongongo nut season is when the diabetic OGTT was taken (Bindon, 2009; Guyenet, 2010; Joffe et al., 1971)

One other non-diabetic OGTT was taken of HG !Kung, not stated when. (Wilmsen, 1982)

!Kung eating non-HG diet did not test diabetic. (H. C. Jenkins et al., 2010)

Mongongo nuts are high in n-6 (Gwatidzo et al., 2017)

Slide 43

1961: soybean oil introduced as an IV food supplement—Intralipid (Gura, 2020)

1964: Noted that Intralipid induces insulin resistance and hyperglycemia (Felber & Vannotti, 1964)

2014: “Infusion of Intralipid, comprised predominantly of polyunsaturated fatty acids [linoleic (44–62%)…]… is an established model for producing lipid-induced insulin resistance.” In humans (Chow et al., 2014; Jensen et al., 2003)

Slide 44

“The lack of… gluconeogenesis in the Clinoleic vs. the Intralipid group suggests that different classes of fatty acids exert different effects on glucose kinetics in preterm infants.”

Proposed mechanism is IR (van Kempen et al., 2006)

Clinoleic is an olive-oil infusion, low in n-6

Of course eating something is vastly different from injecting something

Slide 45

In humans, IR precedes T2DM by years (Martin et al., 1992)

OxLDL is associated with IR, and precedes it by years (Carantoni et al., 1998; Park et al., 2009)

As discussed, seed oils lead to LDL oxidation

Other sources of oxLDL (smoking, sepsis) also induce IR (Attvall et al., 1993; Behnes et al., 2008; Carlson, 2003; Lymperaki et al., 2015)

Unexpectedly,… targeting oxidized LDL [via antibodies] improves insulin sensitivity…” in monkeys (S. Li et al., 2013)

Slide 46

Switching from high to low n-6 oils lowers insulin resistance (Nigam et al., 2014)

Dose-dependent relationship to n-6 content of seed oils

Liver fat also improved—NAFLD patients

“… 15–21% protein… 55–70% carbohydrates, and 20% fats.”

Slide 48

Lowering n-6:n-3 ratio lowers insulin resistance (Van Name et al., 2020)

“The intervention diet consisted of a low n–6 to n–3 PUFA ratio of 4:1…”

“…macronutrient content was 50%–55%... carb., 20% from protein, and 25%–30% from fat…”

Diet monitored by blood biomarkers, including oxLAMs

No control, performed at Yale

Slide 51

“In 1616, Ieyasu Tokugawa, the founder of the Edo government died. It is said he had been overeating fish fried in sesame oil.”

From “Tempura... Another Usage of Lamp Oil”

(Walker, 2003 quoting Ishige, 1980)



References:

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Attvall, S., Fowelin, J., Lager, I., Schenck, H. V., & Smith, U. (1993). Smoking induces insulin resistance—A potential link with the insulin resistance syndrome. Journal of Internal Medicine, 233(4), 327–332. https://doi.org/10.1111/j.1365-2796.1993.tb00680.x

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Bindon, J. R. (2009). Foraging with the !Kung [Educational]. University of Iowa, Anthropology Dept., Unknown. https://anthropology.ua.edu/bindon/ant476/topics/Foragers.pdf

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