The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 11 No. 4 • July 2008


Inflammatory Responses to Eating Mitigated by Certain Nutrients

We have explained in earlier newsletters that eating food, especially high-fat meals, results in an inflammatory state.1,1b New reports suggest that at least part of this food-induced inflammation is due to the stimulation of gut bacteria to release bacterial endotoxins (lipopolysaccharide, LPS),1 which result in the release of inflammatory cytokines. LPS is the major component of the cell walls of gram-negative bacteria and is the primary cause of sepsis, a hyperactive inflammatory immune response to LPS. More important for most people is the positive association between LPS-induced inflammation and insulin resistance; a mouse study found that subcutaneous injections of a low dose of LPS led to excessive weight gain and insulin resistance.1c

For most people in Western countries, there is very little time spent in the fasted state (except during sleep); thus, food-induced inflammation could be taking place most of the time and is therefore importantly related to many inflammation-associated diseases, such as cardiovascular disease, obesity, diabetes, and cancer. Indeed, a recent hypothesis2 proposes that “the reduction in lifetime exposure to infectious diseases and other sources of inflammation . . . has . . . made an important contribution to the historical decline in old-age mortality.”

A recent study1 of 12 healthy men (20–58 years of age) reported that blood endotoxin levels increased significantly by about 50% (as compared to no meal) after a high-fat meal. In another recent study3 of 1015 subjects (in which 201 men had their plasma LPS levels measured), it was reported that endotoxemia was correlated with energy (calorie) intake, e.g., the higher the calorie intake, the higher the level of endotoxemia.

As the authors of Ref 3 also noted, it has recently been shown that “abdominal obesity is associated with a low-grade chronic systemic inflammation.” They also pointed out the association between insulin resistance and the proinflammatory cytokines released by fat tissue in models of diet-induced and genetic obesity. The authors of Ref 3 concluded that “these data suggest that a reduction in plasma LPS concentrations might be a potent strategy for the control of metabolic diseases in humans.”

LPS-Induced Inflammation Reduced

While LPS-induced inflammation is an important part of the immune system’s acute protective responses against bacterial invasion, chronic, low-grade, LPS-induced inflammation is undesirable. Certain nutrients and foods can provide protection.

There are plant constituents (phytonutrients) called proanthocyanidins that can bind and neutralize lipopolysaccharides.4 A recent study of cranberry proanthocyanidins4 (where human embryonic kidney cells were incubated with E coli and either with or without added proanthocyanidin-rich concentrate of cranberry juice) found that the cranberry juice proanthocyanidins inhibited the LPS-induced activation of NF-kappaB, a transcription factor that induces release of proinflammatory cytokines. They identified a mechanism in which the proanthocyanidins actually bind directly to and neutralize LPS by blocking its interaction with certain cell receptors. They cite an earlier study in which a proanthocyanidin-rich fraction of cranberry juice concentrate inhibited the LPS-induced production of the proinflammatory cytokines IL-6 and IL-8, as well as the proinflammatory prostaglandin E2.

Though not tested in this study, other foods that are rich in proanthocyanidins include apple, pear, grapes, blueberries, avocado, chocolate, red wine, tea, and pine bark.5,6

Another recent study7 reported on the results of a gamma-tocopherol supplementation experiment involving 16 human volunteers, some of whom had moderate to severe asthma and others of whom were healthy. Subjects initially took 1 capsule (containing 623 mg of gamma-tocopherol, 61.1 mg of d-alpha-tocopherol, 11.1 mg of d-beta-tocopherol, and 231 mg of d-sigma-tocopherol) per day for 8 days, followed by an 8-day washout period, and then took 2 capsules per day for another 8 days. Peripheral blood monocytes (PBMCs) were collected from each subject and tested by incubating with LPS and measuring proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha, as well as chemokines MCP1 and MIP1beta and the anti-inflammatory cytokines IL-1RA and IL-10.

They found that gamma-tocopherol, but not alpha-tocopherol, “moderately inhibited LPS-induced IkappaBalpha degradation [which activates NFkappaB] in recovered PBMCs after LPS stimulation.” They also found that the LPS-induced secretion of IL-1beta, IL-6, and TNF-alpha and the chemokines MCP1 and MIP1alpha was significantly decreased after treatment with the gamma-tocopherol-enriched supplement. (There was no change in lung function in the asthmatics.)

References

1. Erridge et al. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr 86:1286-92 (2007).
1b. Aljada et al. Increase in intranuclear nuclear factor kappaB and decrease in inhibitor kappaB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect. Am J Clin Nutr 79:682-90 (2004).
1c. Cani et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761-72 (2007), as cited in Membrez et al. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB J 22:2416-26 (2008).
2. Finch and Crimmins. Inflammatory exposure and historical changes in human life-spans. Science 305:1236-9 (2004).
3. Amar et al. Energy intake is associated with endotoxemia in apparently healthy men. Am J Clin Nutr 87:1219-23 (2008).
4. Delehanty et al. Binding and neutralization of lipopolysaccharides by plant proanthocyanidins. J Nat Prod 70:1718-24 (2007).
5. Anon. Oligomeric proanthocyanidins. Altern Med Rev 8(4):442-50 (2003).
6. Gu et al. Screening of foods containing proanthocyanidins and their structural characterization using LC-MS/MS and thiolytic degradation. J Agric Food Chem 51:7513-21 (2003).
7. Wiser et al. In vivo gamma-tocopherol supplementation decreases systemic oxidative stress and cytokine responses of human monocytes in normal and asthmatic subjects. Free Rad Biol Med 45:40-9 (2008).

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