Blood Sugar Levels Effects Taxol

We have seen the claim that any protein you eat in excess of your immediate needs will be turned into glucose by spontaneous gluconeogenesis  . ( Gluconeogenesis (GNG) is the process by which glucose is made out of protein in the liver and kidneys.) Some people think that because protein can be turned into glucose, it will, once other needs are taken care of, and that therefore keto dieters should be careful not to eat too much protein.

While we believe there are valid reasons for limiting protein intake, experimental evidence does not support this one. In our opinion, it makes sense physiologically for GNG to be a demand-driven rather than supply-driven process, because of the need to keep blood glucose within tight bounds.

In brief

• Gluconeogenesis is a slow process and the rate doesn't change much even under a wide range of conditions.
• The hypothesis that the rate of gluconeogenesis is primarily regulated by the amount of available material, e.g. amino acids, has not been supported by experiment. Having insufficient material available for gluconeogenesis will obviously limit the rate, but in the experiments we reviewed, having excess material did not increase the rate.
• We haven't found any solid evidence to support the idea that excess protein is turned into glucose.
• More experiments are needed to confirm that this still holds true in keto dieters.

Gluconeogenesis has a Stable Rate

Gluconeogenesis (GNG) is a carefully regulated process for increasing blood sugar. It is stimulated by different hormones, including glucagon — the primary hormone responsible for preventing low blood sugar. GNG produces glucose slowly and evenly . It was once thought that the main determination of the rate of GNG was how much glucogenic substrate, that is, raw materials for it, was available, but further experiments have shown that this is not the case . Instead, it now appears that GNG is relatively constant over a large variety of conditions .

As an example of this stability, a study by Bisschop et al. in 2000  showed that subjects following a keto diet for 11 days had only a small (14%) increase in glucose production from GNG after overnight fasting, as shown in this graph. This works out to a difference of less than a gram of glucose per hour.

Note that 11 days might be too little time for all of the subjects to , and it is possible that the rate of GNG would change in subsequent weeks.

Negative Results

In another experiment (this time in subjects on a glycolytic, or carb-based, rather than a ketogenic diet), ingesting 50g of protein resulted in the same amount of glucose production as drinking water . In other words, the amount of glucose that was made after ingesting that protein wasn't any more than would have been produced without it. While it's possible that this protein doesn't count as "excess", it was likely to be nearly half of their daily required protein intake, and eaten in one sitting, and so it is enough to cast serious doubt on the idea.

There are other experiments in which increasing the available material for GNG to high levels didn't increase GNG , . In these experiments GNG substrates were infused directly into the blood rather than eaten.

The problem with applying the results of these experiments to the question of excess protein consumption is that infusion might bypass some mechanism that increases GNG when the protein is actually eaten. For instance, it is known that protein consumption stimulates a great deal of glucagon (along with insulin) , and it might be suggested that this glucagon would thereby increase GNG. A counterargument to that possibility is that although glucagon stimulates GNG in many conditions, its action appears to always be overridden by insulin . This means that the insulin that is produced when eating protein will counteract the glucagon and GNG will not be affected (except in the case of insulin-dependent diabetes, where insulin is neither created nor responded to in the normal fashion).

Both the argument from infused substrates and the counter-arguments outlined here are plausible mechanism arguments — taking physiological processes known to occur in one context and arguing that they will occur in another context. Plausible mechanism arguments should be used with caution.

Summary

In sum, then, there is no evidence that we could find that consuming excess protein will increase glucose production from GNG. On the other hand, there is much suggestive evidence that it does not.

Evidence type: experimental

(Emphasis ours)

In the process of protein metabolism, the complex protein molecule is split in the intestinal tract to amino-acids. These are absorbed into the blood stream and transported to the liver where oxidative deamination occurs. Here the glycogenic amino-acids are split to form urea and glucose. That this process is a slow one is shown in the charts by the slowly rising blood urea nitrogen. Glucose is, therefore, liberated into the blood stream in this process at a slow and even rate over a prolonged period of time. Under these conditions the diabetic is able to utilize a greater total amount of glucose without glycosuria in the eight hour period. Therefore, the inability of a diabetic to dispose of large quantities of glucose is partially compensated if the glucose is presented for utilization slowly and evenly. There appears, then, to be some advantage to the diabetic of this slow liberation of glucose from protein foods.

Evidence type: review of experiments

(Emphasis ours)

Gluconeogenesis plays an integral role in the maintenance of glucose homeostasis in humans, contributing about one-third of glucose produced in the postabsorptive state and all glucose produced when hepatic glycogen is depleted by starvation (6, 23-25). Because the results of in vivo experiments in humans and animals (12-15, 20) and in vitro perfused rat liver studies (11, 27) have demonstrated a close correlation between the rate of glucose production and the flux of gluconeogenic substrates, it is believed that gluconeogenic precursor supply plays a major role in the regulation of glucose production (12,13,20). Several studies in vivo support this concept. For example, we and others have demonstrated that the hyperglycemic response to severe burn injury and sepsis is a direct result of an increased rate of glucose production, which is associated with a concomitant increase in the fluxes of alanine and lactate, major gluconeogenic substrates (15, 39). The proposed regulatory role ofprecursor supply received further support in the quest to rationally explain the paradox of a reduced glucose production rate (and hypoglycemia) in starvation, despite a hormonal-substrate milieu that would normally favor stimulation of gluconeogenesis (2, 7, 12, 13, 28), thus glucose production. After prolonged starvation (3-4 wk), human subjects had low levels of gluconeogenic precursors associated with hypoglycemia and a reduced glucose production rate (6, 7, 12, 25). Infusion of unlabeled alanine caused hyperglycemia and an increased incorporation of [ 14C]label from alanine into glucose in this circumstance (12,13). It was therefore proposed by Cahill, Felig, and Marliss and their associates (7, 12, 13, 20) that the reduced glucose production rate in starvation was due to the reduced availability of gluconeogenic substrates; hence, gluconeogenic precursor supply was rate-limiting for glucose production rate. In contrast, the findings of several kinetic studies performed in human

If anyone having access to this paper would like to share it with us, we would be grateful, because it is the most relevant experiment we could find on the topic, and further details may be important.