Nutrition Notes

When a High-Carb Diet is the Answer Instead

Recent trends in nutrition have given preference to high-fat and high-protein diets such as the Ketogenic and Paleolithic diets, respectively, but for good reason. Cardiometabolic conditions such as obesity, diabetes, and cardiovascular disease continue to rise at unprecedented rates and now move into the younger populations. Therefore, the necessity for improving insulin sensitivity, stabilizing blood sugar, and rebalancing fatty acids places the attention on low-carb diets which are effective at accomplishing these tasks. For most Americans, this dietary shift is unarguably helpful in turning the tide on these dangerous health trends.

Yet, among the crowd exists a small population of people whose survival and quality of life may rest upon the availability of glucose, making a higher carb diet the best choice for their health. It is a good reminder that individuality cannot be abandoned and we must continually be mindful of not applying a one-size-fits-all approach even if it benefits the majority.

Amyotrophic Lateral Sclerosis (ALS)

This smaller group of individuals suffers from a condition known as amyotrophic lateral sclerosis (ALS). Although generally known for the rapid degeneration of motor neurons which cause sufferers to rapidly journey from proficient mobility to debilitation in a matter of months or a few years, ALS also involves defective energy metabolism.

ALS shifts its victims in a state of hypermetabolism, which is partly responsible for their rapid deterioration. A decline in skeletal muscle mass, adipose tissue, and body mass index is evidenced by severe weight loss and compounded by dysphagia, mastication and respiratory difficulty. Malnutrition ensues and exacerbates weakness and lack of mobility.

The etiology behind ALS-associated hypermetabolism is elusive. Patients experience increased energy expenditure while resting, which is normally the opposite response to malnutrition. Defective mitochondrial function in the liver, muscle, and spinal neurons either caused from genetic polymorphisms or accelerated calcium release warrants some consideration. Others have suggested problems with the hypothalamic signaling pathways or leptin-induced thermogenesis in skeletal muscle as well as leptin-induced neurological signaling that controls brown adipose tissue thermogenesis and glucose metabolism in skeletal muscle. Hypermetabolism in ALS has been either measured by or associated with increased glucose uptake and utilization. Part of this activity may be due to increased activity of glycolysis and Krebs cycle enzymes such as hexokinase, phosphofructokinase, citrate synthase, and malate dehydrogenase.

Hypermetabolism also affects the brain of ALS patients. PET scans combined with 18F-fluorodeoxyglucose (FDG), a specific radiotracer for glucose metabolism, of the brains of 37 ALS patients showed hypermetabolism in medial temporal lobe and cerebellum which affected cognitive function.


Evidence for a High-Carb Diet

The requirement for a high-calorie diet for ALS sufferers is universally accepted as calorie restriction has been associated with a poor prognosis. But the question becomes whether the excess calories should be given as glucose (through a high-carb diet) or fatty acids (via a Ketogenic diet). It would seem that studies are ambivalent and both forms of high-calorie diets perform well with ALS. In a double-blind, placebo-controlled, multi-center clinical trial of 20 ALS patients without a history of diabetes, significant liver or cardiovascular disease, subjects were divided into 3 groups that received either an isocaloric diet (controls), a high-carbohydrate hypercaloric diet (HC/HC), or a high-fat hypercaloric diet (HF/HC) for four months. After five months, the HC/HC diet was found to be the most easily tolerated with few serious adverse events and fewer discontinuations compared to the control and HF/HC diet group. While the HF/HC group did not experience any deaths as did the control group, it was not statistically different from the control group in adverse events, tolerability, deaths or disease progression. While this study favors the use of a high-carb diet over a high-fat due to greater tolerability and fewer adverse effects, it also acknowledges a small sample size and lack of adherence from the HF/HC group.

In another study, published in 2019, using a Drosophila model of ALS, it was reported that the alteration of glycolytic metabolites and genes, as well as the upregulation of key genes responsible for driving glucose metabolism, were consistent with increased glucose consumption. In a fly model, increasing dietary glucose improved locomotor function and increased lifespan. It was also reported that “genetic over-expression of human glucose transporters improves locomotor function, mitigates neuromuscular junction defects, and improves lifespan in a variant dependent manner.” Similarly, “motor neuron overexpression of PFK, the rate-limiting enzyme in glycolysis, improves locomotor function, suggesting that upregulation of glycolysis is neuroprotective through a compensatory mechanism in ALS.” The study concluded that increasing glucose availability served to protect motor neurons and improve clinical outcomes in ALS models.

The recommendation to increase glucose in ALS patients has been suggested previously because of its ability to reduce protein misfolding and delay neuronal degeneration in C. elegans models of neurodegeneration.

Evidence for a Ketogenic Diet

Despite evidence for a high-carbohydrate, high-calorie diet in ALS patients, other researchers show beneficial evidence for the use of a Ketogenic diet. An increase in Krebs cycle intermediates such as arginine-alpha-ketoglutarate (AAKG) which is amply supplied in a Ketogenic diet improved neurological score and motor performance in mice models of ALS. In Mutant SOD1 transgenic mouse models of ALS, a ketogenic diet generally had protective effects on ALS; however, did not address the oxidative stress implicated in ALS progression.

In summary, a high-calorie diet is critical for the longevity of ALS patients but the question remains as to whether those calories should be supplied primary by carbs or fatty acids. The jury is still out regarding a winner (and maybe both will prove successful), but the evidence does show a high-carbohydrate diet is well tolerated and beneficial for improving clinical outcomes of ALS and therefore, we should acknowledge that there may be a place for carbs, after all.