In the May issue of The Journal of Nutrition there is an interesting new study on salivary amylase variability and postprandial glycemic response to starch consumption by Abigail Mandel and Paul Breslin. It has a very small sample size so we should be reserved about drawing conclusions until further research is done but the results sure hint at a pretty extreme example of individual genetic variability to starch consumption.
Salivary amylase of course is the first step in starch digestion, but the amount between different people can vary by quite a bit due to things like stressors (you can manipulate concentrations with a beta blocker!) or genotype. With regard to the latter, there was a really fascinating study published in 2007 that found a correlation between the number of salivary amylase gene (AMY1) copy numbers and enzyme levels and the starch content of the population’s diet in which the individuals were from. PZ Myers has a nice post on it here. In 2010, a paper was published that showed AMY1 copy number again predicts salivary amylase concentration and activity level, and influences oral perception of starch. This is a highly suggestive example of evolution in action in response to the dramatic increase in starch in many populations since the agricultural revolution.
Until recently, according to the authors of the new paper, it wasn’t understood if salivary amylase added much to digestion: food passes through the mouth rather quickly, and we have pancreatic amylase anyway for starch digestion. And, AMY2 (pancreatic amylase) doesn’t show the copy number variability that AMY1 does, suggesting AMY1 may be of greater significance to starch metabolism. In addition, studies have found that swallowing whole starchy foods results in lower blood glucose concentrations than when chewed, and that starch itself protects salivary amylase from the acidity of the stomach.
But what does this do to blood glucose concentrations after ingestion in people who have more salivary amylase compared to those who have less? This is what they studied. They hypothesized (as common sense would suggest) that those with more salivary amylase would have a higher postprandial glucose response, since they would break down starch faster and more efficiently. But that is not what they found!
The study consisted of 10 “high amylase” (enzyme concentrations per minute calculated by salivary flow rate that were 1 standard deviation higher than group (n=48) mean) and 9 “low amylase” (1 standard deviation lower) participants. Side note: they have the subjects chew on a square of parafilm for 90 seconds before collecting the saliva sample. With a google search I see this is commonly used for this which makes me wonder 1) who originally stuck some in his/her mouth and thought “hey lets use this!” and 2) why I now feel obliged to chew on some too. On 2 occasions, the subjects consumed (after fasting overnight) 50 grams of a corn starch hydrolysate solution or 50 grams of a glucose solution (as the control; salivary amylase obviously does not act on glucose!). These were consumed over 20 minutes, during which their rate was monitored, and they were instructed to swish every sip around their mouth for ~5 seconds prior to swallowing. Blood samples were collected intermittently over 2 hours for plasma glucose measurements and to measure AMY1 copy numbers. Lastly, they assessed the diets of each subjects with a food frequency questionnaire to see if there was a relation to self-selected starch intake (there was not). The authors write that “5 individuals were removed from the analysis based on the exclusion criteria described in the “Methods,” but I could find no such criteria (hmm?). This left 7 subjects in each group.
They found a positive correlation (r=0.90, p<0.0001) between amylase concentration and AMY1 gene copies number. Here is a table with group characteristics:
As you can see salivary flow rate, salivary amylase concentration and activity were all significantly higher in the high amylase group, along with the AMY1 copy number.
Here is the most interesting result: the high amylase group had lower plasma glucose responses after consuming the starch solution than the low amylase group at 45, 60, and 70 minutes (p<0.01, p<0.001, and p<0.01, respectively), as well as a lower AUC (89 +/- 21 vs 244 +/- 55 mmol/L over 120 minutes, p<0.05) and lower peak glucose (9.56 +/- 0.43 vs 7.57 +/- 0.35 mmol/L, p<0.01). Resting blood glucose was not different between the groups.
Here is plasma glucose after the consumption of starch solutions (darker line is the low amylase group):
To convert from mmol/L to mg/dL (what we more commonly understand glucose concentrations in), multiply by 18.02. At the hour time-point (the greatest difference), that gives us about (visually estimating from the graph) 150 mg/dL in the low amylase group compared to about 110 mg/dL in the high amylase group. A ~40 mg/dL difference at this point is quite large.
Interestingly, plasma insulin concentrations were not different between the groups at any of the time-points when analyzed over the whole period, but the high amylase group had higher insulin at the 9 minute point when analyzed separately, as well as a higher AUC from 0-9 minutes. They found a moderate correlation (r = 0.70, p<0.01) between this AUC and oral amylase produced per minute. I am a bit skeptical about these because these are during the time when the subjects are consuming the solution, and the rate of consumption though monitored couldn’t have been exactly equal in each, and apparently none of this was blinded. But here is the graph:
There were no differences between the groups for the control glucose solution for plasma glucose or insulin (at any time-point, AUC, or peak, or within the first 9 minutes).
Finally, they analyzed for differences within each group as well and found that the low amylase group had a larger postprandial glucose AUC following the starch solution compared to the glucose solution, and a higher glycemic index for the starch solution than the high amylase group (111 +/- 7 vs 94 +/-3, p<0.05) which is interesting to consider.
Why would people with more salivary amylase have a lower glucose response to starch consumption? The authors suggest that the higher plasma insulin concentration within the first minutes during consumption may mediate this, even though there were no overall differences in insulin responses to starch or glucose between the groups. They make a reasonable case why this could be, even though I am not sure this data alone is very convincing.
The rise of insulin within the first 15 minutes of consumption is “preabsorptive,” (or the cephalic phase) because no glucose has been absorbed yet. Insulin rises here in part because of a conditioned/anticipatory (Pavlovian) response to the flavor or smell of food. Research has demonstrated that this initial response is important for normal glucose tolerance in animals and humans, even though it is only a small part of total insulin release. According to the data here, the low amylase group did not show this preabsorptive insulin release to starch consumption but they did to the glucose solution, while the high amylase group showed for both. This may suggest that salivary amylase actually stimulates this insulin phase in some way. The authors suggest that perhaps low concentrations (too low to perceive) of glucose and/or maltose from some starch digestion in the mouth triggers T1RS-T1R3 (sweet) taste receptors or glucose transporters in taste receptor cells. Or, short-chain oligosaccharides produced might bind to the “putative polysaccharide receptor.” Or, “hormones or incretins are peripherally released by lingual taste cells into the blood stream in response, stimulating insulin release from the pancreas during the PIR [preabsorptive] period,” for which they provide no references (how is that not challenged in peer-review?).
Clearly much work obviously remains to test these theories.
The authors suggest that the differences in blood glucose may underlie some of the differential development of insulin resistance and diabetes between populations. It is possible- there is a strong observational link between postprandial glycemia and many chronic diseases. This of course needs much more study to verify. Is it possible that AMY1 gene copy number could help in risk assessment? It is an intriguing hypothesis.
I would really like to see this replicated in high and low amylase groups with real foods instead of swishing solutions which may exaggerate the differences (though actually probably better represents the reality in which most in industrialized countries consume them!), and with more subjects to reduce the effect of intra-individual plasma glucose measurement variation (and other random variation) but fascinating nonetheless!
Mandel, A. L., & Breslin, P. A. S. (2012). High Endogenous Salivary Amylase Activity Is Associated with Improved Glycemic Homeostasis following Starch Ingestion in Adults. The Journal of Nutrition. doi:10.3945/jn.111.156984