Wheat: Raises Insulin and Upregulates 'Bad' Genes

Ancient Wheat: 'Gladiator '
'Now We Are Free' Hans Zimmer, Lisa Gerrard

Can our food alter gene expression?

Absolutely so!

As Hippocrates once said, 'Let food by thy Medicine... and Medicine thy Food.' I'm sure he didn't mean medications as they exist now as chemicals or benzene rings (derived from petroleum) mass synthesized in factories for global consumption. The below FUNGENUT study recently showed the importance of how different sources of carbohydrate containing foods immediately changes gene expression in our favorite organ -- the omentum -- the stubborn fat lying on our bellies -- yes, the one covering up your those fabulous 6-pack abs. (Diagram: Ludwig, D. (2002) JAMA )

In a small group of subjects, 2 diets (Rye-Pasta -- mildly lower in GI; Oat-Wheat-Potato -- high GI carbs) were compared for 3 months. At the end no change in weight or insulin resistance, insulin levels, or glucose concentrations occurred. The profile for insulin (1st phase) secretion mildly improved in the Rye-Pasta group.

Interestingly, other than showing that wheat sucks (and perhaps oat and potato) gene expression was entirely affected by simple changes in carbohydrate content and the Glycemic Index (GI measures how long and how fast glucose enters the blood stream after consumption). Rye (endosperm) bread has a GI (glycemic index) of approximately 60-70. Pasta's GI is about 60-70 as well (depending on the type and how al dente/not-overcooked).

Wheat bread on the other hand is about 90-100 (close to pure glucose). Oats about 70 and potatoes 80-100 (without cream or butter which slows the uptake of starches into the stomach blood circulation which would effectively lower the GI). American Russet potato even exceeds glucose, 110 (!wow).

CARBOHYDRATE COMPOSITION OF FOOD PROVIDE MOLECULAR EFFECTS AND LOW-GI CARBS DOWNREGULATE 'BAD' GENES:

"Prior microarray studies found differences in gene expression between overweight and lean individuals (2) and after energy restriction (3); however, changes in the ratio of fat to carbohydrate did not alter gene expression (3). The study by Kallio et al makes a significant contribution to the literature by demonstrating the potentially major effects of dietary composition on gene regulation, independent of energy intake and body weight. Two specific findings concerning the low-insulin-response diet merit particular attention: the down-regulation of both hormone-sensitive lipase (HSL) and TCF7L2. "

"HSL, a key enzyme in the release of fatty acids from adipose tissue, has been proposed to affect body weight and metabolic variables. Mice made deficient in HSL by genetic manipulation are resistant to genetic- or diet-induced obesity (4, 5). Women carrying an allele associated with decreased HSL activity have lower fasting and simulated insulin concentrations, and men with this allele have lower nonesterified fatty acid concentrations (6)..."

"The transcription factor TCF7L2 is the strongest known genetic predictor of type 2 diabetes. A microsatellite within intron 3 of this transcription factor occurs with increased frequency in individuals with type 2 diabetes, which corresponds to an estimated population attributable risk of 21% (7)..."

"The present study (BELOW) has direct implications concerning our understanding of the dietary glycemic index (GI). The GI is a system for classifying carbohydrate-containing foods according to how blood glucose concentrations change in the postprandial period (reviewed in reference 8). High-GI meals produce greater postprandial insulin concentrations and C-peptide excretion than do nutrient-controlled low-GI meals. Observational and interventional studies have linked GI to the risk of obesity, diabetes, heart disease, and cancer, although the topic remains much debated. One factor contributing to this ongoing controversy is the relative paucity of data regarding the relevant molecular mechanisms. If differences in insulin secretion mediate the genetic effects observed by Kallio et al, similar effects would be expected to occur with both low-GI and high-GI diets. This possibility is supported by a human study and several rodent studies, which showed potentially beneficial changes in the expression of HSL and other relevant genes with a low-GI diet (8, 9)."

Contrastingly, the high-GI wheat (+oat+potato) diet upregulated 62 genes including those associated with activation of DEATH GENES:
-- Stress
-- Oxidative damage
-- Impaired immunity

So... high carb diet translates to... the equivalence of a STRESS RESPONSE. The authors discuss in more depth the results from the FUNGENUT Study..."Interestingly, the 12-wk oat-wheat-potato diet seemed to especially activate genes responding to stress. The oxidative stress pathway, interleukin pathway, and inflammation mediated by the chemokine and cytokine signaling pathway were also activated. Moreover, the present data suggest that the oat-wheat-potato diet, which induced repeated high insulin responses, can provoke alterations in immune status and inflammation. It is well established that adipose tissue has a role in inflammation (39). Cross-sectional epidemiologic data suggest that whole grains and a low-glycemic-index diet may reduce systemic inflammation in women with T2DM (40). Up-regulation of gene expression for serum and glucocorticoid-regulated kinase suggests activation of the glucocorticoid axis, which can occur in response to various stress stimuli (cytokines, aldosterone, growth factors, oxidative stress, heat shock protein activation, and glucocorticoids) (41). Activation of the pituitary-adrenal glucocorticoid axis may be involved in the pathogenesis of the metabolic syndrome (42)."

Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT Study.
Kallio P, et al. Am J Clin Nutr. 2007 May;85(5):1169-70.
Department of Clinical Nutrition, Food and Health Research Centre, University of Kuopio, Kuopio, Finland.
BACKGROUND: Diets rich in whole-grain cereals and foods with a low glycemic index may protect against type 2 diabetes, but the underlying molecular mechanisms are unknown.
OBJECTIVE: The main objective was to test whether 2 different carbohydrate modifications--a rye-pasta diet characterized by a low postprandial insulin response and an oat-wheat-potato diet characterized by a high postprandial insulin response--affect gene expression in subcutaneous adipose tissue (SAT) in persons with the metabolic syndrome.
DESIGN: We assessed the effect of carbohydrate modification on SAT gene expression in 47 subjects [24 men and 23 women with a mean (+/-SD) age of 55 +/- 6 y] with the features of the metabolic syndrome in a parallel study design. The subjects had a mean (+/-SD) body mass index (kg/m(2)) of 32.1 +/- 3.8 and a 2-h plasma glucose concentration of 8.0 +/- 2.3 mmol/L. Adipose tissue biopsies were performed, and oral-glucose-tolerance tests and other biochemical measurements were conducted before and after the intervention.
RESULTS: We detected 71 down-regulated genes in the rye-pasta group, including genes linked to insulin signaling and apoptosis. In contrast, the 12-wk oat-wheat-potato diet up-regulated 62 genes related to stress, cytokine-chemokine-mediated immunity, and the interleukin pathway. The insulinogenic index improved after the rye-pasta diet (P=0.004) but not after the oat-wheat-potato diet. Body weight was unchanged in both groups.
CONCLUSIONS: Dietary carbohydrate modification with rye and pasta or oat, wheat, and potato differentially modulates the gene expression profile in abdominal subcutaneous adipose tissue, even in the absence of weight loss.
PMID: 17490981

These wonderful graphs from Finland researchers illustrate how the toxic effects of grain sources of carbohydrates occur when wheat and rye are fed to healthy volunteers. Above a glucose blood concentration of 150 mg/dl (=8.3 mmol/L), glucose starts to cause changes in protein folding and glycosylating proteins and tissues. Diabetes micro-vascular complications like eye/kidney/nerve ending damage are related to toxic concentrations of glucose. Imagine sugar coating the organs over time. The higher the concentration, the longer the duration, the more thicker and more damaging the sugar coating. Insulin is controlled by several factors. Food is one of the most potent controllers, with carbohydrates and their respective GIs raising insulin levels the most. Excessive insulin induces inflammation, which can progress and cause arterial stiffness, high blood pressure, Metabolic Syndrome, obesity, and also heart disease. Longevity has been associated with lower insulin levels. The below trial demonstrates the direct relationship in 18-year old men between fasting insulin and the existence of cardiovascular markers. The curves for low or no GI foods have no peaks and in comparison are relatively flat. Without a surge in insulin, inflammation is kept at bay.

Foods with no or little GI:
-- Non-starchy vegetables
-- Protein (tofu, meat, fish, etc)
-- Monounsaturated fat
-- Omega-3 PUFA
-- Saturated fat

The goal for an optimzed health status for nearly all metabolic and cardiovascular goals is NORMAL. Therefore the optimal range for insulin is as low as possible less than 5 - 10 mIU/L. The goal for glucoses pre-meal is less than 83 (=4.6mmol/L) and after meals less than 110 to 120 (=6.1 to 6.67mmol/L).

Relationship between fasting insulin and cardiovascular risk factors is already present in young men: the Verona Young Men Atherosclerosis Risk Factors Study.
Bonora E, et al. Eur J Clin Invest. 1997 Mar;27(3):248-54.
The associations between fasting plasma insulin concentration and risk factors for cardiovascular disease were examined in 979 18-year-old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. Body mass index (BMI), waist-to-hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high-density lipoprotein (HDL)-total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low-density lipoprotein cholesterol, concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles (F = 7.1; P less than 0.001). However, systolic blood pressure and uric acid were close to statistical significance (P = 0.06-0.07). Multiple linear regression analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e, three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables (F = 4.0; P less than 0.01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides. PMID: 9088862