Identifying genetic blockages in metabolic pathways and implementing targeted nutrition interventions for the prevention and treatment of muscle wasting
Key Highlights
- Common variants in one-carbon nutrient pathways can lead to muscle damage in genetically susceptible individuals.
- By identifying these patients with an easily administered genetic test, healthcare providers can target nutrition treatments to each patient’s specific needs for maximum benefit.
- SNP Therapeutics has developed a genetic test and nutritional formulation that accurately diagnoses identifies and treats patients with muscle wasting caused by one-carbon nutrient deficiencies.
- Giving patients the knowledge and tools to directly influence their immediate and long-term health outcomes is a simple but effective way to improve overall wellness and lower healthcare costs.
Introduction
Muscle wasting, also known as sarcopenia, occurs when the body has difficulty converting dietary protein into muscle mass. This condition represents a significant burden for patients and the healthcare system as a whole. It is a prevailing health condition that affects 32 million Americans and is expected to account for up to $4 billion in healthcare costs by 2024.
Muscle wasting is associated with age-related muscle loss and can lead to significant muscle atrophy and cachexia, which compound the problem by causing decreased appetite and energy levels. Research indicates that up to 10% of muscle wasting cases are due to genetic misspellings called single nucleotide polymorphisms (SNPs) that affect genes involved in one-carbon nutrient pathways.
People with a common set of gene variants (single nucleotide polymorphisms; SNPs) develop muscle loss whenever they eat diets low in 1-Carbon nutrients (for example choline, betaine, methyl folate) placing them at higher risk at higher risk of muscle wasting.
SNP Therapeutics has designed a genetic test in which hundreds of related SNPs are examined using an algorithmic approach based on a machine learning/AI platform. In this way, the test determines each patient’s genetic profile, also known as their genetic signature, specific to the genes involved in one-carbon nutrient metabolic pathways. Using information about that patient’s genetic signature, a nutrition supplementation program is developed to meet their metabolic needs.
This is what makes gene-guided nutrition treatments stand out from traditional nutrition therapies. Within the U.S. population, individuals do not metabolize nutrients to the same extent or with the same degree of efficiency, due to misspellings in each person’s genetic code that can affect both the requirement and metabolism of various nutrients. Using genetic testing to identify aberrations in one-carbon nutrient genes, followed by the application of precision nutrition treatments to address the pathways affected, is a sophisticated yet simple way to improve patient outcomes and lower the risk of future complications from muscle wasting.
Impacts of Genetics and Ethnicity on Muscle Wasting
In a 2014 study measuring the effects of a low-one-Carbon nutrient diet on men and women, approximately 10 % of the people studied developed muscle damage that stopped when these nutrients were added back to the diet.1 Six SNPs in the SLC44A1 gene and one SNP in the CHKB gene occurred with greater frequency in patients who developed choline deficiency–related muscle dysfunction.
Both SLC44A1 and CHKB play integral roles in muscle function. SLC44A1 codes for the transporter required to move choline through plasma and across mitochondrial membranes. In addition, misspellings in the CHKB gene in both mice and humans result in muscular dystrophy by shutting off the function of the choline kinase B enzyme, demonstrating the direct impact that these genetic errors can have on muscle function.2 The SNPs studied in SLC44A1 and CHKB appear to be related, as 90% of study subjects who developed muscle damage on the low-choline diet had both effect alleles as opposed to only one.
Ethnicity also plays a role in the occurrence of SNPs related to muscle wasting. Multiple studies have found differences between Caucasians and African Americans regarding these alleles and even the function of one-carbon nutrient pathways, leading to differential profiles of fat deposition in the liver. Interestingly, the 2014 study noted above found that none of the Asian-American subjects were carriers of a SLC44A1 effect allele associated with muscle damage, whereas 24% of the other ethnic groups in the study had a specific effect allele on this gene. In contrast, over 70% of subjects of African descent had at least one copy of an effect allele for SLC44A1 and/or CHKB, placing them at higher risk of muscle wasting from choline deficiency.
The Role of One-Carbon Nutrients in Muscle Wasting
Along with genetic factors, nutritional status and diet composition are linked to both the development and treatment of muscle wasting. The one-carbon nutrient choline is essential for cell structure and function throughout the body, including the musculoskeletal system. Not only is choline involved in the synthesis of the primary cell membrane component phosphatidylcholine, but it also participates in the transport of lipids from the liver. Choline is a major methyl donor as well through its metabolite betaine.4 Finally, choline acts as a precursor to acetylcholine, a neurotransmitter that is essential for a multitude of signaling processes including muscle contraction.5
The current adequate intake (AI) for choline is 425 mg/day for non-pregnant women and 550 mg/d for men.6 Pregnant women have an increased choline requirement (450 mg choline/day) to meet their baby’s needs for rapid development of the brain and central nervous system. Women who consume choline-deficient diets while pregnant or breastfeeding place themselves at risk of harmful effects and their babies at markedly increased risk of birth defects such as neural tube defects and cognitive impairment.
Unfortunately, most Americans consume a choline-deficient diet which can lead to liver damage, fatty liver, and muscle damage. In people with the SNPs discussed above, insufficient dietary choline could place them at even higher risk for muscle wasting and its related health consequences.
Because one-carbon nutrients are connected by their functions in interrelated metabolic pathways, deficiencies in one nutrient (caused by low dietary intake or genetic anomalies) can affect the body’s requirement for another nutrient. For instance, individuals with a common effect allele SNP of in the MTHFD1 enzyme gene are at increased risk of deleterious effects from both choline and folate deficiency. When consuming a low-choline diet, these individuals develop symptoms that can only be resolved with the supplementation of choline and methyl folate.7
With patients taking part in genetic testing and nutrition counseling to assess their needs for one-carbon nutrients as well as their risk of muscle wasting, the quality of life for many thousands of patients could be improved and the burden on our country’s healthcare system significantly lessened.
SNP Therapeutics Genetic Test for Muscle Wasting
SNP Therapeutics has developed a genetic test and a medical nutrition treatment approach for individuals at risk of muscle wasting that could prevent the condition in a significant subset of patients.
By examining multiple genes within interrelated pathways through an algorithmic approach rather than focusing only on single genes, SNP Therapeutics has developed a powerful and accurate method for identifying patients at high risk of muscle wasting.
A significant number of cases could potentially be prevented by identifying effect alleles in certain genes before clinical signs develop, then initiating medical nutrition changes targeted to the nutrient pathways that are affected by each patient’s genetic signature.
Considerations for Practice
SNP Therapeutics’ genetic test and precision nutrition approach can identify and treat patients at risk of muscle wasting based on their genetic profile. Using each patient’s test results, an individualized nutrition care plan can be implemented to prevent the development or progression of this potentially fatal disease.
Gene-guided nutrition is the future of individualized healthcare. By tailoring nutrition treatment plans for each patient’s genetic signature, health outcomes could look very different for the next generation.