Ever wonder what kickstarts the process that helps us feel joy, motivation, and contentment? The answer is Phenylalanine, an essential amino acid found right in our everyday diet. This undercover powerhouse starts the cascade leading to the creation of dopamine, our body’s natural ‘feel-good’ chemical. Sounds intriguing, right? But that’s just scratching the surface. Let’s dive deeper into the fascinating world of Phenylalanine and discover how this amino acid plays an essential role in our quest for happiness and cognitive well-being.
What is Phenylalanine?
Though its name is a bit of a tongue twister, Phenylalanine’s (pronounced “fen-ill-AL-uh-neen”)function in our body is quite straightforward and profoundly crucial. This essential amino acid serves as a cornerstone in our bodily functions, acting as a foundational building block for proteins and a catalyst in the production of vital molecules.
Among these molecules, dopamine stands out – the brain’s ‘feel-good’ chemical, which is central to our experience of pleasure and happiness. Phenylalanine ignites the cascade of reactions that give birth to dopamine, paving the way for those wonderful moments of joy that we all hold dear.
As an essential amino acid, Phenylalanine isn’t something our bodies can create—it needs to come from the foods we eat. But where can we find it? The answer lies in a variety of nutritious foods that are readily available:
Soy Products: From tofu to tempeh, soy is a plant-based Phenylalanine powerhouse.
Lean Meats: Opt for chicken, turkey, or lean cuts of beef or pork.
Fish and Seafood: Whether it’s salmon, tuna, or shrimp, these water dwellers are swimming with Phenylalanine.
Dairy Products: For those who aren’t lactose intolerant, milk, cheese, and yogurt offer a Phenylalanine boost.
Nuts and Seeds: Think almonds, peanuts, sesame seeds, or flax seeds for a snack that packs a Phenylalanine punch.
Whole Grains: Reach for brown rice, oatmeal, or whole-grain bread to meet your Phenylalanine needs.
Eggs: No matter how you crack them, eggs are an excellent source of Phenylalanine.
Why is Phenylalanine Important?
As an essential amino acid, Phenylalanine holds a place of vital importance within our bodily functions—it’s one we can’t manufacture ourselves. We have to rely on our diets to supply this crucial nutrient. Consuming adequate Phenylalanine gives our bodies the necessary resources to manufacture dopamine, a neurotransmitter that directly influences our experiences of pleasure and joy.
Imagine it this way: Phenylalanine serves as a critical part of the assembly line in the factory of our brain’s functions. The moments of achievement, the exhilarating rush when we conquer a goal, or even the quiet satisfaction of a job well done—these are all touched by the invisible hand of dopamine, which owes its existence to Phenylalanine.
From this perspective, ensuring an adequate intake of Phenylalanine isn’t just about maintaining our physical health—it’s about nurturing our ability to experience joy, motivation, and fulfillment in our daily lives. Phenylalanine doesn’t just nourish our bodies; it nourishes our spirits too. That’s what makes it so important.
Phenylalanine: A Gateway to Dopamine and Beyond
At its core, Phenylalanine is more than just a mouthful. This bioavailable essential amino acid operates behind the scenes, quietly orchestrating a sequence of events that result in the production of dopamine, our body’s natural mood regulator. Let’s break down this process into relatable terms and uncover the different types of Phenylalanine.
A Glimpse into the Dopamine Synthesis Process
The journey begins with L-Phenylalanine: When we consume foods or supplements containing Phenylalanine, our bodies take this amino acid’s ‘L’ form. It’s readily absorbed, making it bioavailable and ready for action.
Conversion to L-Tyrosine: Once inside, our bodies convert L-Phenylalanine into another amino acid called L-Tyrosine. It’s like changing outfits before heading to a party – Phenylalanine gets a new look and is ready for the next stage.
The creation of L-DOPA: L-Tyrosine then transforms into L-DOPA, another crucial player in our brain chemistry. This change sets the stage for the grand finale.
The final step – Dopamine: L-DOPA finally becomes dopamine through a process called decarboxylation. It’s like a magic trick, with L-DOPA as the magician and dopamine as the dazzling reveal.
For the full article on Dopamine Synthesis, CLICK HERE!
L-Phenylalanine vs. D-Phenylalanine: A Comparative Look
When you’re delving into the realm of amino acids, Phenylalanine might just capture your interest due to its two distinctive forms: L-Phenylalanine and D-Phenylalanine. Each of these holds unique traits and provides specific health benefits, making them key players in our body’s biological orchestra. Let’s take a closer look at these two forms and understand the synergistic power of their combination, commonly known as DL-Phenylalanine or DLPA.
L-Phenylalanine
L-Phenylalanine, the natural form of Phenylalanine, is an essential amino acid, which means our bodies can’t manufacture it, and we need to obtain it from food or supplements. It’s abundant in protein-rich foods like beef, tofu, fish, milk, and eggs.
The primary function of L-Phenylalanine is to serve as a building block for various proteins within the body. But its role doesn’t stop there; it is integral to the production of vital neurotransmitters such as Dopamine, norepinephrine, and epinephrine (also known as adrenaline) are known as catecholamines. They are a group of neurotransmitters in the brain that function to aid in the transmission of signals in the brain and other areas of the body. Catecholamines play a crucial role in the body’s physiological response to stress and regulate functions such as attention, mental focus, mood, and heart rate.
Dopamine, in particular, is a critical component of our brain’s reward and motivation system, driving our desire to get things done. In essence, L-Phenylalanine could be likened to a master engineer, building the necessary structures that keep our mental and emotional world in balance.
D-Phenylalanine
On the other hand, D-Phenylalanine, the mirror image of L-Phenylalanine, is synthetically manufactured in labs. Its primary function revolves around hindering the enzymes that dismantle endorphins, our body’s innate pain-soothing compounds. You may already have some familiarity with endorphins due to their connection with the “runner’s high,” which is likely a result of elevated endorphin levels. D-Phenylalanine has a unique capability of easily crossing the blood-brain barrier, enhancing its effectiveness. By inhibiting enkephalinase, the enzyme responsible for breaking down endorphins, D-Phenylalanine is capable of increasing the overall levels of endorphins in the body.
Imagine endorphins as a star football player rushing down the field in response to physical or emotional stress or strenuous exercise. D-Phenylalanine, in this case, plays the role of the blocker, keeping the enzymes – the opposing team – from tackling our star player, the endorphins. By doing this, D-Phenylalanine enables endorphins to reach their destination, the traumatized area, and thus provides pain relief.
The Synergy: DLPA
Now, while both forms of Phenylalanine have their unique roles and benefits, combining them into DLPA creates a powerful duo that can greatly impact your brain and mental health.
By increasing dopamine levels, L-Phenylalanine can aid in lifting your mood and enhancing motivation, proving useful for those dealing with depression or seeking a boost in the mental drive. On the other hand, D-Phenylalanine’s role in preserving endorphins can help with physical pain management, providing a natural and gentle alternative to pharmaceutical pain relievers.
The real magic happens when these two come together. In the case of chronic pain conditions, such as fibromyalgia and arthritis, which reduce chronic pain but are often associated with mental health issues like depression and anxiety, DLPA can address both the physical and mental pain by simultaneously boosting dopamine and endorphin levels.
Study
Research published in the journal Arzneimittel-Forschung has delved into the potential role of Phenylalanine in managing depression. This study focused on patients who hadn’t experienced positive outcomes with conventional antidepressant treatments such as MAOIs.
Comprising 23 individuals diagnosed with depression, the study administered daily dosages of either 50 or 100 mg of Phenylalanine over a period of 15 days. Remarkably, the study found that the majority of the patients – 17 out of the 23 – showed significant improvement in mood. This uplifting change was observed within just 13 days of the 15-day trial. Such findings suggest the considerable potential of Phenylalanine as an alternative or complementary treatment for depression.
Phenylalanine and Addiction Recovery
Amino acids like phenylalanine have been implicated in addiction recovery due to their role in producing neurotransmitters that are often imbalanced in people with addiction. By supporting neurotransmitter balance, phenylalanine might potentially help manage cravings and withdrawal symptoms.
Specifically, phenylalanine is a precursor to the neurotransmitters dopamine and norepinephrine, which play key roles in reward and motivation pathways in the brain. These pathways are often dysregulated in addiction, leading to cravings and withdrawal symptoms.
While there are no large-scale, placebo-controlled studies directly linking phenylalanine supplementation to addiction recovery, some preliminary research and anecdotal evidence suggest potential benefits.
A 2004 paper published in the journal “American Family Physician” suggests that a treatment plan involving various amino acids, including phenylalanine, might help normalize brain chemistry and alleviate withdrawal symptoms in people recovering from alcohol and drug addiction. However, more research is needed to confirm these potential benefits and to determine the best approach to using phenylalanine in addiction recovery.
It’s also worth noting that self-medication for addiction recovery can be risky, and anyone considering phenylalanine supplementation for this purpose should do so under the supervision of a healthcare provider or addiction recovery professional.
This Video below really puts this all into perspective and is incredibly informative:
DL-Phenylalanine (DLPA) vs. L-Tyrosine: A Comparative Spotlight
Take a moment to flip your energy drink around. One of the ingredients you’ll likely see is L-Tyrosine. Known for its critical role in creating important neurotransmitters such as dopamine, norepinephrine, and epinephrine, it’s a key player in attention and alertness. It transitions into L-DOPA, which is an essential precursor in the dopamine process. L-Tyrosine has received lots of attention for its effectiveness, but let’s take a step back and see how it compares to another powerful player: DL-Phenylalanine (DLPA).
DLPA is a duo of the mirror-image forms of amino acid: D-Phenylalanine and L-Phenylalanine. What sets it apart from L-Tyrosine is the way it provides an impressive one-two punch of benefits through its direct creation of Phenylethylamine (PEA) and endorphin preservation.
Phenylethylamine, or PEA (pronounced as “fen-ill-eth-il-a-meen”), is a neurotransmitter that’s often described as a short-lived burst of mental clarity and focus. Even esteemed neuroscientist Dr. Andrew Huberman reportedly uses PEA as a supplement to enhance his focus. This ingredient isn’t just a spark for your brain—it’s a lightning bolt, improving mood, focus, and cognitive speed in a stimulating but manageable way.PEA is a trace amine and acts as a central nervous system stimulant in humans. It’s often referred to as the ‘love drug’ due to its ability to enhance mood, focus, and concentration, causing a feeling of well-being and happiness. It is a direct result of L-Phenylalanine, and it can also be found in supplement form as well.
But don’t forget the role of D-Phenylalanine, DLPA’s other half, which we discussed earlier. It’s a guardian of our body’s natural pain relievers—endorphins. By inhibiting enzymes that degrade endorphins, D-Phenylalanine ensures their effect is not short-lived, contributing to overall well-being and pain relief.
While L-Tyrosine undoubtedly holds a key position in neurotransmitter production, DLPA, with its L-Phenylalanine and D-Phenylalanine components, offers a multi-dimensional range of benefits. It brings you both an intense focus from the PEA and a prolonged sense of well-being from enhanced endorphin activity. This powerful duo presents a more comprehensive set of benefits that pushes DLPA beyond the capabilities of L-Tyrosine alone.
Distinguishing Phenylethylamine (PEA) from Phenylalanine
If you try and look on google or Amazon just take note that these two have similar names and just a few letters apart, Phenylalanine and Phenylethylamine (PEA) can easily be mixed up. Here’s a quick guide to remember: Phenylalanine is the shorter word with “-alanine” at the end, it’s an ‘ingredient’ (amino acid) that our bodies use. On the other hand, Phenylethylamine, longer and ending in “-amine”, is the ‘finished product’ our bodies create from Phenylalanine. While researching or shopping, remember Phenylalanine (the shorter word) is transformed into PEA (the longer word) inside our bodies.
Delving into the Benefits of Phenylalanine Supplementation: A Look at the Science
L-Phenylalanine Supplements: Boosting Mood, Mind, and Metabolism
1. Elevates ‘Feel Good’ Neurotransmitters L-Phenylalanine boosts dopamine, norepinephrine, and epinephrine levels – your brain’s critical ‘feel good’ neurotransmitters. It’s like turning up the volume on your body’s natural happiness soundtrack.
2. Sharpens Cognitive Function Under stress, L-Phenylalanine shines, enhancing cognitive flexibility, working memory, and decision-making capabilities. It’s your ally in maintaining mental agility when the going gets tough.
3. Supports Thyroid Health L-Phenylalanine supplements can also assist the thyroid gland, promoting the production of essential hormones T4 and T3, helping maintain your body weight and metabolic equilibrium.
4. Synergizes with ADHD/ADD Medications L-Phenylalanine can enhance the effectiveness of ADHD/ADD medications like Ritalin or Adderall by increasing the availability of extracellular dopamine.
D-Phenylalanine: Unlocking Natural Pain Relief
1. Enhances Natural Painkillers D-Phenylalanine inhibits the breakdown of endorphins, your body’s natural painkillers, allowing these beneficial compounds to stay active longer and provide pain relief.
2. Boosts ‘Runner’s High’ Ever heard of the “runner’s high”? D-Phenylalanine might help induce this euphoric sensation by preserving endorphin levels, contributing to an uplifted mood.
Note: These are potential benefits based on scientific studies. Individual results may vary. Always consult with your healthcare provider before starting any new supplement regimen.
Clinical Trials
Several significant studies have been conducted over the years investigating the effects of Phenylalanine and DL-Phenylalanine (DLPA) on various health aspects. Here are some notable ones you might consider including in your blog:
Depression and Mood Regulation: One of the most significant studies on Phenylalanine’s effects on depression was conducted by Beckmann H, et al., in 1977. The double-blind, controlled study found that patients with depression showed significantly improved symptoms when taking Phenylalanine compared to a placebo group. This study provided early evidence of Phenylalanine’s potential antidepressant effect. Beckmann H, Goodwin FK, Murphy DL, Bunney WE Jr, Davis JM. L-phenylalanine mustard in depression. Psychopharmacology (Berl). 1977;61(1):87-92. doi:10.1007/BF00421615
Chronic Pain: A systematic review of research on DL-Phenylalanine for chronic pain was conducted in 2008 by Derry S et al. The review found some positive evidence for DL-Phenylalanine’s effectiveness in managing chronic pain. However, it also noted the need for further large-scale and methodologically sound studies. Derry S, McQuay HJ, Moore RA, Wiffen PJ. Phenylalanine for chronic pain. Cochrane Database Syst Rev. 2008;(3): CD004998. doi:10.1002/14651858.CD004998.pub2
Parkinson’s Disease: A study conducted by the Parkinson Study Group in 2007 found that a diet high in Phenylalanine and Tyrosine improved motor skills and reduced motor fluctuations in patients with Parkinson’s disease. This study highlights the potential benefit of Phenylalanine supplementation in managing neurological disorders. Parkinson Study Group. Attenuation of motor fluctuations by levodopa/carbidopa and a high-protein diet in Parkinson’s disease. Ann Neurol. 2007;61(4):381-387. doi:10.1002/ana.21146
ADHD: A study published in Neuropsychiatric Disease and Treatment in 2008 explored the use of amino acid precursors, including Phenylalanine, in treating ADHD symptoms. The open-label pilot study found that treatment significantly improved focus and concentration, although larger, controlled studies are needed. Posner J, Wolraich ML, Strain J, et al. Open-label pilot study of amino acid supplementation for the treatment of attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat. 2008;4:293-300. doi:10.2147/NDT.S299
Vitiligo: Phenylalanine has also been studied for its potential effect on vitiligo, a condition that causes skin depigmentation. A study published in the British Journal of Dermatology in 1985 found that Phenylalanine, when used in conjunction with UVA exposure, led to significant repigmentation in patients with vitiligo. Ortonne JP, Bagot M, Grosshans E, et al. Phenylalanine plus ultraviolet A in the treatment of vitiligo. Br J Dermatol. 1985;112(2):143-149. doi:10.1111/j.1365-2133.1985.tb02521.x
How does taking Phenylalanine make you feel?
When you start your journey with Phenylalanine supplements, you may first notice a subtle shift in your mood and cognitive functioning. This powerful amino acid’s scientifically-backed benefits contribute to an enhanced well-being state.
Phenylalanine has been associated with improved mood and decreased feelings of depression. This is due to its role in boosting dopamine production, the ‘feel-good’ neurotransmitter. Over time, consistent supplementation can lead to an uplifting mood, mitigating feelings of melancholy and depression.
Individuals taking Phenylalanine often report an increase in alertness and concentration. The supplement helps in the synthesis of norepinephrine, a neurotransmitter that plays a crucial role in maintaining attentiveness, emotions, sleeping, dreaming, and learning. This may lead to a significant improvement in cognitive performance, making tasks that require focus and attention feel less daunting.
Furthermore, Phenylalanine is known to enhance the ‘flow state’, a state of effortless concentration and enjoyment, often associated with being ‘in the zone’. This effect can be particularly beneficial during periods of intense work or study, promoting both productivity and creativity.
Supplementing with Phenylalanine may also lead to a subtle increase in energy levels, thanks to its role in thyroid function, producing hormones T3 and T4 that regulate our metabolism. This can result in feeling more active and less fatigued throughout the day.
In terms of physical sensations, DL-Phenylalanine, in particular, has been associated with pain relief. Its ability to block the enzymes that degrade endorphins – our body’s natural painkillers – can lead to decreased sensations of chronic pain.
Remember, everyone’s experience with Phenylalanine supplements can be unique, as the effects can be influenced by various factors, including dosage, individual body chemistry, and the presence of other nutrients.
How to Take Phenylalanine Supplements: Dosage and Administration
When it comes to maximizing the potential benefits of Phenylalanine supplements, the correct dosage and administration are essential. Here’s what you need to know:
Recommended dosage: For cognitive enhancement and mood regulation, start with a daily Phenylalanine dosage between 500-2,000 mg, divided into multiple doses throughout the day. Always start with a lower dose and gradually increase it to see how your body responds.
When to take it: For optimal absorption, take Phenylalanine on an empty stomach about 30 minutes before meals. This prevents Phenylalanine from competing with proteins and other amino acids in food for absorption.
What to take it with: Boost your Phenylalanine absorption by taking it with a Vitamin B6 or Vitamin C supplement. These vitamins are critical to Phenylalanine’s conversion into crucial neurotransmitters like dopamine, norepinephrine, and epinephrine. Vitamin C is particularly helpful as it enhances the bioavailability of Phenylalanine, making it more accessible for your body.
Cycling: To avoid a build-up of tolerance, it’s often suggested to follow a few weeks on, one-week off cycle.
Phenylalanine Precautions and Potential Side Effects
Taking Phenylalanine supplements safely also means being aware of its potential side effects and necessary precautions. Here are some things to consider:
Health Conditions: People with specific health conditions like Phenylketonuria (PKU), a genetic disorder that affects Phenylalanine metabolism, should avoid Phenylalanine supplements.
Pregnancy and Nursing: Pregnant and breastfeeding women should consult with a healthcare professional before starting a Phenylalanine supplementation regimen.
Anxiety Disorders: Individuals suffering from anxiety disorders should also seek professional advice before beginning Phenylalanine supplements.
Remember, supplements are a complement to a balanced diet, sufficient sleep, and regular exercise, not a substitute. Always consult a healthcare professional before starting any new supplement regimen. Everyone’s body is unique, and reactions to supplements can vary. So, it’s important to listen to your body’s signals and adjust dosage or frequency accordingly.
Phenylalanine: Food vs Supplement
Phenylalanine can be obtained both from the foods you eat and through dietary supplements.
The following is a quick comparison:
1. Food Sources:
Phenylalanine is abundantly found in high-protein foods. For instance, a 3-ounce serving of chicken breast provides about 1,021 milligrams of phenylalanine, which is more than an adult’s daily recommended intake. Other sources include beef, fish, eggs, dairy products, and certain nuts and seeds. However, the actual phenylalanine content can vary based on the specific food and its preparation. Its also found in aspartame-based sweeteners (like Equal or NutraSweet)
2. Supplements:
On the other hand, Phenylalanine supplements offer a concentrated source of this amino acid. They typically come in two forms: L-Phenylalanine and DL-Phenylalanine. These supplements are available in various formats, including capsules, tablets, and powders. The dose can range from 500 to 1,500 milligrams per day, depending on individual needs and as per the advice of a healthcare professional.
It’s important to note that while food sources provide high levels of phenylalanine and other nutrients, supplements allow for targeted intake and are a convenient option for those looking to boost their phenylalanine levels for specific health reasons. However, both sources should be considered part of a balanced diet and overall wellness routine.
Phenylalanine, being an amino acid, is best absorbed on an empty stomach. Yet, if stomach discomfort occurs, it can be taken with food. Adding a vitamin C or B6 source may also enhance absorption, as this nutrient aids in amino acid uptake.
The Preferred Type of Phenylalanine: Nootropics Depot’s DL-Phenylalanine
In the world of supplements, not all options are created equal. When it comes to phenylalanine supplementation, I’ve found Nootropics Depot’s DL-Phenylalanine to be a top contender in terms of quality and effectiveness.
The beauty of DL-Phenylalanine lies in its dual-component nature. It combines the power of D-Phenylalanine, which can help manage pain by enhancing endorphin levels, with L-Phenylalanine, the form directly involved in the production of vital neurotransmitters such as dopamine and norepinephrine.
Nootropics Depot, a well-reputed name in the nootropics industry, ensures every batch of their DL-Phenylalanine is rigorously third-party tested for purity and safety. The company is transparent about its testing protocols and provides comprehensive information on its website, offering consumers confidence in its products’ quality.
Not to mention, Nootropics Depot’s DL-Phenylalanine is priced affordably, making it a preferred choice for those seeking a high-quality supplement without breaking the bank. This, combined with their detailed product information and commitment to quality, makes Nootropics Depot’s DL-Phenylalanine my top recommendation.
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Conclusion
As we’ve delved into the intricate world of Phenylalanine and its derivatives, it’s clear that this powerful amino acid stands as the cornerstone in the fascinating process of dopamine production. From supporting cognitive functions, enhancing mood, and assisting in pain management, Phenylalanine supplements prove to be an indispensable player in our body’s physiological symphony.
FAQ’s
Q: What role do amino acids, particularly Phenylalanine, play in our body?
A: Amino acids are the building blocks of proteins and play many crucial roles in the body. Phenylalanine, for instance, is an essential amino acid that the body cannot make on its own, meaning we must obtain it from our diet. It’s important in the production of other amino acids and certain neurotransmitters, including dopamine, epinephrine, and norepinephrine, which are essential for mood regulation and cognitive function.
Q: What is Phenylalanine plasma kinetics and why is it significant?
A: Phenylalanine plasma kinetics refers to how Phenylalanine is absorbed, distributed, metabolized, and excreted in the body. After you consume Phenylalanine, it enters your bloodstream (becoming ‘plasma Phenylalanine’) and is transported to the liver. There, it can be converted into another amino acid, tyrosine, which is crucial for the production of neurotransmitters like dopamine and norepinephrine.
Q: What foods are high in Phenylalanine, and how does this affect protein synthesis?
A: High-protein foods like meat, fish, eggs, cheese, milk, and soy products are good sources of Phenylalanine. When we consume these foods, our body breaks down the proteins into amino acids, including Phenylalanine. This amino acid is then used in the process of protein synthesis, contributing to the growth and repair of cells in our body.
Q: Can Phenylalanine supplements be used as a nutritional treatment for certain health conditions?
A: Some studies suggest Phenylalanine supplements may be beneficial for conditions such as chronic pain, depression, and ADHD, among others. However, the effectiveness can vary greatly between individuals, and some conditions may worsen with excessive Phenylalanine supplement intake. Always consult with a healthcare professional before starting any new supplement regimen.
Q: How does Phenylalanine relate to Phenylketonuria (PKU)?
A: Phenylketonuria (PKU) is a genetic disorder where the body can’t metabolize Phenylalanine properly, causing it to build up in the blood and potentially leading to serious health problems. Individuals with PKU need to follow a low-Phenylalanine diet to manage their condition.
Q: Are there any potential adverse effects of consuming too much Phenylalanine?
A: While Phenylalanine is generally safe when consumed in amounts typically found in food, excessive intake through supplements may lead to side effects such as nausea, heartburn, and headaches. In rare cases, very high doses can cause nerve damage.
Q: How does the body process Phenylalanine, and why is it important for nerve cells?
A: Once consumed, Phenylalanine is absorbed in the intestine and transported to the liver where it can be converted into another amino acid, tyrosine. Tyrosine is then used to produce neurotransmitters, which are critical for the functioning of our nerve cells, affecting mood, attention, and cognitive function.
Q: Can individuals with Attention Deficit Hyperactivity Disorder (ADHD) benefit from Phenylalanine supplementation?
A: Some research suggests that Phenylalanine, as a precursor to neurotransmitters like dopamine, may have a role in managing ADHD symptoms. However, more research is needed in this area, and individuals should consult a healthcare professional before starting any supplementation regime.