Trait#57: Betaine Requirement Trait

Monday, March 09, 2020. Author FitnessGenes

Betaine Requirement Trait

What is betaine?

Betaine, also known as trimethylglycine (TMG), is a key molecule that is used in a series of metabolic reactions called the methionine-cycle. Specifically, betaine is used for an important methylation reaction, where it helps recycle homocysteine into methionine. In the broader context of the body, betaine is required for a healthy liver and cardiovascular system. It also is needed for optimal exercise performance. 

 

Betaine was first discovered in sugar beets (hence the name ‘betaine’) and is also found in high quantities in foods such as wheat bran, spinach and shrimp. We can also make (synthesize) betaine from choline, which we encountered in your previous trait: Choline Synthesis and Metabolism

Your Betaine Synthesis and Metabolism trait analyzes how effectively you produce and use betaine, which influences how much betaine you need to get from your diet. 

KEY POINTS

  • Betaine is a key nutrient needed for important metabolic reactions in the body, good cardiovascular and liver health, and optimal exercise performance. 
  • We both obtain betaine from our diet and produce it ourselves from choline.  

 

What are the roles of betaine in the body?

Betaine carries out an important metabolic reaction as part of the methionine-cycle, which has widespread effects in the body. Additionally, betaine plays an important role in maintaining cell volume and hydration status. 
 

Betaine and the methionine cycle

Betaine plays a crucial role in the methionine-cycle. This is a series of reactions that metabolize the essential amino acid methionine, generating other important molecules in the process.   

We described the methionine-cycle in the Choline Synthesis and Metabolism blog, and readers are encouraged to revisit that article for an overview. 

 

During the methionine cycle, methionine from protein in our diet gets converted into another amino acid called homocysteine. The job of betaine is to recycle homocysteine back into methionine. 

In a type of reaction called methylation, betaine donates a methyl group (-CH3) to homocysteine, thereby converting it back into methionine. This reaction is catalysed by an enzyme called BHMT (betaine: homocysteine methyltransferase). 

In the wider context of the body, betaine’s action in the methionine cycle is important for three main reasons:

  • it regulates levels of homocysteine, a potentially harmful molecule.
  • it provides a supply of methionine for building proteins.
  • it helps to produce SAM (S-adenyl-methionine), a key molecule needed for methylation reactions (such as those involved in making proteins, cell signalling and switching genes on and off).

Let’s take a look at each of these in turn. 

 

Regulation of homocysteine levels

Homocysteine is an amino acid that is produced during the methionine cycle. High levels of homocysteine in the blood (known as homocysteinaemia) are linked to an increased risk of heart attack, stroke and dementia. 

By recycling homocysteine back into methionine, betaine prevents the accumulation of homocysteine, keeping blood homocysteine levels in check. On this note, betaine is sometimes used as a treatment for people with inherited forms of homocysteinaemia. 

 

KEY POINTS

  • Homocysteine is an amino acid produced by the methionine cycle. 
  • High levels of homocysteine are linked to cardiovascular disease. 
  • Betaine prevents levels of homocysteine from rising. 

 

Providing a supply of methionine to make proteins 

Methionine is an example of an amino acid – the building blocks of proteins. A steady supply of methionine is needed to make important proteins, such as enzymes, hormones and structural proteins. 

As an essential amino acid, we cannot make methionine (de novo) ourselves and must obtain it from our diet. Nevertheless, we can maintain methionine supplies by regenerating it from homocysteine. As we’ve seen, this process relies, in part, upon the methylation of homocysteine by betaine.

 

KEY POINTS

  • Betaine replenishes stores of methionine for building enzymes, hormones and other proteins. 

 

Production of SAM 

One of the key molecules produced in the methionine cycle is called S-adenyl-methionine (SAM). SAM is important in the body because it acts as a universal methyl donor. This means it takes part in various methylation reactionswhere it donates a methyl-group (-CH3) to other molecules. 

 

Methylation by SAM is important for several biological functions, including:

  • switching genes on and off (i.e. changing gene expression)
  • producing proteins
  • producing neurotransmitters (nerve-signalling molecules)
  • making creatine – an important fuel source for muscles during intense, short-term exercise.

SAM is derived from methionine. By recycling homocysteine back into methionine and therefore keeping methionine levels high, betaine drives the production of SAM


KEY POINTS

  • Betaine helps to produce SAM (S-adenosyl-methionine).
  • SAM is used for various methylation reactions that are important for making proteins, switching genes on and off, and making creatine. 

 

Regulation of cell volume

Outside of its role in the methionine cycle, betaine ensures cells are hydrated and keep their volume and structure. In this respect, we describe betaine as an osmolyte

If you can remember your high school biology lessons, water tends to move from a high concentration to a low concentration in a process called ‘osmosis’. Betaine regulates osmosis, allowing sufficient amounts of water to remain inside cells. This, in turn, maintains cells’ volume and structure. 

When cells lose their structure, crucial enzymes in their membranes may cease to function. Furthermore, cells can be damaged by sudden changes in volume and water concentration – a phenomenon known as “osmotic stress.’ By maintaining cell volume and structure, betaine helps to protect various cells (especially muscle and kidney cells) from osmotic stress. 

KEY POINTS

  • Betaine helps cells to maintain their water content and therefore volume and structure. 
  • Betaine protects cells from damage caused by rapid changes in water content and volume (osmotic stress). 

 

How is betaine made?

Betaine is derived from the essential micronutrient choline. You can learn more about choline in the Choline Synthesis and Metabolism blog

Choline is converted into betaine in two stages. In the first stage, choline is made into betaine aldehyde. This stage is catalysed by the choline dehydrogenase (CHDH) enzyme, which is encoded for by the CHDH gene. 

 

In the second stage, betaine aldehyde is converted into betaine by the enzyme betaine aldehyde dehydrogenase (BADH). 

Variants of the CHDH gene can affect the activity of the CHDH enzyme, which, in turn, influences how well you produce / synthesize betaine. This will impact upon your need to obtain betaine from diet and/or supplements. 

KEY POINTS

  • Betaine is made from choline by the CHDH and BADH enzymes. 
  • Variants of the CHDH gene affect how well you make betaine. 

 

How is betaine metabolized?

Betaine’s main role in the methionine cycle is to recycle homocysteine back into methionine. In this methylation reaction, betaine (or trimethylglycine) donates a methyl-group to homocysteine and, in doing so, gets converted into dimethylglycine (DMG)

This reaction is carried out by the enzyme betaine homocysteine methyltransferase (BHMT), which is encoded by the BHMT gene

Variants of the BHMT gene can affect the activity of the BHMT enzyme. This influences how much betaine your body uses and, consequently, how much betaine you need to obtain from your diet. 

The BHMT enzyme also needs zinc to work effectively, so it's important to get enough zinc in your diet to ensure healthy betaine metabolism. 

KEY POINTS

  • Betaine is metabolized by the BHMT enzyme for use in the methionine cycle.
  • Variants of the BHMT gene affect how much BHMT you use. 

 

Betaine and exercise performance

A healthy intake of betaine is needed for good exercise performance. 

There is some evidence that taking betaine supplements can enhance athletic ability, although the findings are mixed. The ergogenic (i.e. performance-enhancing) effects of betaine may result from its impact on creatine production. 

 

Betaine and creatine

As mentioned earlier, betaine is important for the production of SAM (S-adenosyl-methionine), which in turn helps to generate creatine. 

Creatine is part of the phosphagen energy system, which provides rapidly available energy for roughly 10 seconds of intense exercise. We therefore use this system for short-duration activities such as sprinting and weightlifting. 

 

In order to contract, our muscles require chemical energy in the form of ATP. We store some ATP in our muscles, but these stores are small and only sufficient to fuel 1-2 seconds of maximal exercise. Luckily, we can quickly generate more ATP using a fuel source called phosphocreatine (creatine phosphate). During intense exercise (e.g. sprinting), phosphocreatine gets converted into creatine, yielding more ATP for a further 5 - 8 seconds of effort. 

When we subsequently recover a bout of exercise, we quickly reconvert creatine into phosphocreatine, thereby replenishing our energy stores. 

So, how does betaine fit in? Betaine is important for making SAM (S-adenosylmethionine), which helps convert a molecule called guanidoacetic acid into creatine. 

 

It’s thought that betaine improves exercise performance by increasing the production of creatine and phosphocreatine, allowing for longer bursts of maximum effort

On this note, a study of sprinters found that betaine supplementation significantly increased time to exhaustion.

Betaine supplementation has also been linked to improvements in strength/ resistance performance. For example, in one study, subjects consumed 2.5g of betaine supplements over 14 days and experienced significant increases in power and force production for vertical jump, bench throw, bench press and isometric back squat exercises. 

In addition to its effect on creatine, improvements in strength may result from betaine’s role in maintaining cell volume. By ensuring they retain their structure and are well hydrated, betaine may make muscle cells more resistant to the osmotic stress that occurs during intense resistance training.  

Despite the above findings, there are still several studies that suggest that betaine supplementation has little or no effect on athletic performance. A 2017 systematic review of the literature concluded that there is a lack of clear evidence to support betaine supplementation for improvements in strength and power performance, with further studies being needed.

KEY POINTS

  • Betaine supports the production of creatine and phosphocreatine.
  • Phosphocreatine is used for energy in short, intense exercise under 10 seconds. 
  • Betaine helps exercise performance by producing creatine. 
  • Betaine supplements may enhance exercise performance but the evidence is limited. 

 

Genetics

Your trait analyzes gene variants tied to two main processes:

  • betaine synthesis (production) by CHDH.
  • betaine metabolism (usage) by BHMT.

If you carry CHDH gene variants related to reduced betaine synthesis, you may need to consume more betaine in your diet and/or consider betaine supplements. 

Similarly, if you have BHMT gene variants assocated with increased betaine metabolism, your body will use up more betaine. You may therefore require more betaine in your diet or via supplements. 

Be sure to check out your insights and actions for more information on how to optimize your betaine intake. 

KEY POINTS

  • Your trait analyzes variants of your CHDH and BHMT genes. 
  • If you have reduced production and/or increased usage of betaine, you may more require more betaine in your diet. 

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