Oxaloacetate Supplements: Early Research + Side Effects

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It’s a natural part of your energy metabolism. Its proponents claim that it will increase your lifespan, but can it be stabilized for long enough to make a difference? What can oxaloacetate really do? Read on to find out.

Oxaloacetate, an organic molecule, is part of the body’s energy production and waste management systems. It is absolutely essential in infant development; a genetic deficiency in the enzymes that make oxaloacetate can cause serious neurological problems and developmental delays [1, 2, 3].

Researchers have only just begun to unlock its therapeutic potential. In a handful of studies on worms, oxaloacetate was found to significantly increase lifespan. These studies, among others, have led to a minor surge in oxaloacetate supplementation, but studies on worms cannot and should not be extrapolated to human health [4, 5].

That’s one of the reasons why these supplements are controversial. Others include the fact that oxaloacetate is very difficult to stabilize, oral supplements may not be well absorbed, and the worm studies have yet to be repeated in higher animals, let alone people [6].

What’s more, the company that manufactures most oxaloacetate supplements has a history of violating FDA regulations regarding the marketing and sale of “new drugs” and “medical foods” [7].

With all this in mind, it’s not surprising that research into oxaloacetate has been highly contentious.

The Citric Acid Cycle

The citric acid cycle, otherwise known as the Krebs cycle (or tricarboxylic acid cycle), is one of the cell’s primary means of energy production [8, 1].

Oxaloacetate sits between malate and citrate in the cycle. Malate is transformed to oxaloacetate when it donates a hydrogen atom to NAD to make NADH; NADH then goes on to help generate energy from sugar. An enzyme called pyruvate carboxylase can also convert pyruvate into oxaloacetate [8, 9].

Oxaloacetate can transform into citrate (part of the cycle) or any one of six amino acids [8].

NAD & NADH

In the citric acid cycle, malate donates hydrogen to NAD to make oxaloacetate and NADH. However, this reaction also takes place in the reverse: oxaloacetate takes a hydrogen atom from NADH to make malate and NAD [4].

High levels of NAD, relative to NADH, may support other age-related mechanisms in the cell. These include the sirtuins and AMPK, which have been linked to increased lifespan and reduced rates of degenerative diseases in animal models [10, 4].

Glutamate Scavenging

Oxaloacetate reduces glutamate levels by breaking it down (to α-ketoglutarate).

More specifically, when oxaloacetate and glutamate encounter an enzyme called glutamate oxaloacetate transaminase (or GOT), the enzyme transforms them both, and they emerge as aspartate and α-ketoglutarate. In medical research, this is called glutamate scavenging, and it could help prevent high levels of glutamate from building up in the brain and becoming destructive [11, 12].

This mechanism is somewhat controversial. One study found that oxaloacetate protected against cell death from hydrogen peroxide, but not from glutamate. Future research will work out these contradictions and determine whether glutamate scavenging is relevant to human health [1].

• Part of the body’s natural energy system
• Protects the brain from toxins and injury
• May increase lifespan and prevent age-related disorders
• May lower blood sugar
• May prevent PMS
• May protect the heart and kidneys

• May worsen the symptoms of Parkinson’s disease
• Few clinical studies for any benefit
• Many claims with no human studies at all
• Many assumptions based on animal studies (including worms)
• High risk of bias in prominent studies
• Difficult to stabilize in supplement form
• Expensive
• Better alternatives available for most health goals

Researchers are investigating whether oxaloacetate supplements could have benefits to human health, but clinical trials are either lacking or contradictory. The FDA has furthermore not approved oxaloacetate supplements for any medical purpose or health claim.

Better-studied alternatives are available for all of the health benefits oxaloacetate is purported to have. We recommend talking to your doctor about these alternatives before adding any new supplements to your regimen.

Oxaloacetate is central to energy use in all known living things. It is part of the citric acid cycle, also known as the Krebs cycle (or tricarboxylic acid cycle), which releases the energy stored in carbohydrates, fats, and proteins [13, 1].

Limited human studies suggest that 100 to 1,000 mg of oral oxaloacetate salt may reduce blood glucose, increase insulin sensitivity, and improve symptoms in people with diabetes [14, 15].

Note that these claims are controversial. A human safety study found that 200 mg per day of oral oxaloacetate did not significantly affect levels of oxaloacetate in the blood [16].

Much more research is therefore required to determine whether oxaloacetate supplements could be useful in controlling blood sugar.

No clinical evidence supports the use of oxaloacetate for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

We recommend strongly against attempting to use oxaloacetate for any of the health claims discussed below. Talk to your doctor about the many better-studied alternatives available.

Glutamate is an important neurotransmitter; however, large quantities of glutamate can contribute to brain damage. Oxaloacetate, in combination with an enzyme called glutamate oxaloacetate transaminase or GOT, breaks down glutamate (into 2-ketoglutarate and aspartate) [11, 17].

The degree to which this may be applicable to oxaloacetate as a supplement is unclear.

Pesticides

Organophosphates are toxic chemicals used as pesticides. Malathion, for example, is commonly used to control insects and treat head lice and scabies [18, 19, 20].

About a million people suffer from organophosphate pesticide poisoning every year. These poisons cause seizures, brain and nerve damage, and – in hundreds of thousands of cases – death [11].

Glutamate appears to be the culprit behind the seizures and secondary damage. Some authors have therefore suggested that oxaloacetate may protect the nervous system from the worst effects of pesticide poisoning. In a rat study, an injection of oxaloacetate and the human GOT enzyme reduced blood glutamate and protected against brain damage [11].

This strategy is called “blood glutamate scavenging” and some researchers believe that it may become an important tool in the management of pesticide poisoning [11].

Traumatic Brain Injury

After traumatic brain injury, glutamate levels rise and neurons die. In a rat study, a high dose of intravenous oxaloacetate reduced cell death and protected the animals’ brains [21].

A second rat study confirmed this effect; it also demonstrated that combining oxaloacetate with two other compounds (pyruvate and lipoamide) dramatically decreased glutamate in the brain [12].

Subarachnoid hemorrhage (SAH) is one of the most dangerous types of stroke, with nearly half of patients dying in the first month after the event. Glutamate is likely responsible for severe brain damage in such cases [22].

In rats, intravenous oxaloacetate reduced blood glutamate by half in the first 90 minutes after stroke. The treatment also protected the blood-brain barrier and reduced the amount of lasting damage in the rat brain [22].

The effect of oxaloacetate has not been studied in human stroke victims. However, high levels of the glutamate-degrading GOT enzyme predict better outcomes for people who have suffered a stroke [23].

Alzheimer’s and Parkinson’s Diseases

Alzheimer’s disease is a complex degenerative disease that changes the brain in many ways. People with Alzheimer’s have fewer mitochondria, reduced insulin and increased inflammation in their brains [24].

In rats with Alzheimer’s disease, oxaloacetate encourages the formation of new mitochondria, activates insulin signaling, and reduces brain inflammation. It may even promote the birth of new neurons [24].

This effect has not been studied in human trials. Furthermore, in a small clinical trial, nearly 40% of participants receiving oxaloacetate supplements experienced a worsening of Parkinson’s disease symptoms, though none of these symptoms were considered severe [25].

Much more research is required to determine whether oxaloacetate has a role in managing Alzheimer’s and Parkinson’s diseases.

Commercial oxaloacetate supplements often come with claims that they will increase the lifespan of their users. Terra Biological LLC, which manufactures the oxaloacetate supplement benaGene, has even published its own study claiming that their product extends lifespan by imitating the effects of calorie restriction [15].

Is it true? Can oxaloacetate make you live longer?

In Caenorhabditis elegans, a species of worm often used to study aging, oxaloacetate increased lifespan by 13% on average [26, 4, 5].

Oxaloacetate also reduces the formation of a compound called methylglyoxal, which damages proteins and organelles within cells. And this compound impairs wound healing, which can be especially dangerous for diabetics [26, 4, 5].

Interestingly, methylglyoxal is also what lends manuka honey strong bacteria-fighting properties; at the same time, it hints at this honey’s dark side [27].

In a study of mitochondria, oxaloacetate protected an enzyme called citrate synthase, levels of which drop with aging [28].

Researchers have not yet duplicated these protective effects in live mammals such as mice, rats, or humans. In one study, mice supplemented with oxaloacetic acid did not live longer than the controls. However, oxaloacetate is notoriously unstable and degraded significantly before the mice could consume it in their feed [6].

In short: some early research suggests a link between oxaloacetate and longevity, but there isn’t nearly enough evidence to recommend taking oxaloacetate. Any supplement bottle’s promises of a longer life are a stretch at best and deliberately misleading at worst.

Nearly half of all women on the planet suffer some form of PMS or Premenstrual syndrome; in some countries, such as Iran, it is almost universal [29].

Scientists don’t fully understand what causes PMS, but they have some ideas. One possibility is that, because menstruation is such an energy-intensive process, glucose metabolism shifts toward the reproductive system and away from other systems – including the brain [29, 30, 31].

According to this hypothesis, PMS (and its more serious cousin, premenstrual dysphoric disorder) are caused by energy deficits in the parts of the brain that govern self-control [29, 30, 31].

At least one oxaloacetate supplement is sold with claims of reducing PMS symptoms: its manufacturers say that it supports glucose metabolism and scavenges glutamate in the brain. One clinical trial of 48 women was reported as complete in April 2018. However, the results have not been posted, and no other studies support these claims [32].

Caloric restriction – or, deliberately reducing food intake – has been shown to prevent age-related disorders and increase longevity in many animals, including mice and primates. Some compounds, including antioxidants like resveratrol, imitate the effects of caloric restriction by activating similar pathways in the body [33].

Oxaloacetate may boast a similar effect. In one C. elegans worm longevity study, oxaloacetate activated a signaling pathway associated with caloric restriction and longer life [4].

If oxaloacetate mimics caloric restriction in humans as it does in C. elegans, it may reduce the risk of heart and kidney diseases. However, no studies have yet drawn a direct connection between oxaloacetate and these risks [34, 35].

According to some researchers, oxaloacetate may have some potential as a supportive therapy in the treatment of brain cancer. Brain tumors thrive when glutamate levels are high; in mice and rats, oxaloacetate reduced glutamate, shrank tumors, and improved survival rates [36].

In an aggressive type of pancreatic cancer, cancer cells break down the amino acid glutamine to accelerate their growth. In this and several other types of cancer, blocking the tumor’s ability to use glutamine may stop it from growing and make it more sensitive to chemotherapy and radiation [37, 38].

In mice, oxaloacetate reduced glutamine breakdown and decreased cancer cell growth rates. It may also, therefore, make chemotherapy and radiation treatments more effective [37].

Oxaloacetate may also reduce the growth of tumors by selectively blocking mitochondrial complex II, which may starve cancer cells of energy [39, 40].

This early research is not grounds to use oxaloacetate supplements if you are undergoing cancer treatments. Talk to your doctor about better-studied complementary approaches.

Oxaloacetate is available in capsule form. One company, Terra Biological LLC, claims to have developed a method for stabilizing oxaloacetate and making it bioavailable when taken orally.

This company manufactures benaGene and Jubilance, the most prominent oxaloacetate supplements on the market. However, these supplements have not been evaluated by any third party labs, so there’s no way to be sure of what’s actually in them.

Most oxaloacetate supplements also list several other compounds in their ingredients, such as vitamins C and B12.

Oxaloacetate is present in some foods, but not in high enough levels to impact health. It is also highly unstable and readily degrades over time [6, 24].

Your body can also make oxaloacetate from malate or malic acid – at least in theory.

Malic acid is what gives fruits and some vegetables a sour taste. It was first discovered in apples, but a wide range of fruits contain it. These include grapes, mangos, pears, oranges, and many more. Whether these foods can boost oxaloacetate levels is unknown.

There is no safe and effective dose of oxaloacetate because no significantly powered study has been conducted to find one.

Oral supplements are typically sold at a dosage of 100 – 200 mg per day. Pilot studies have tended to use doses in this range, which are generally well tolerated. However, some researchers suggest that 200 mg of oral oxaloacetate has very little effect on the levels of oxaloacetate in the blood, suggesting that higher doses should be studied [41, 16].

Most animal studies demonstrating the health benefits of oxaloacetate used injections directly into the body cavity or the veins. Oral supplements have not been studied as extensively.

No adverse effects have been reported in clinical studies of diabetic people using doses of up to 1,000 mg per day. One study found that doses of 200 mg per day had no effect on blood levels whatsoever [14, 16].

In a small clinical trial of oxaloacetate and Parkinson’s disease, 7 out of 18 (39%) people reported that their symptoms had gotten worse, compared with 1 out of 15 (7%) taking the placebo. If you have Parkinson’s disease, it may be wise to avoid oxaloacetate until further research is conducted [42].

No safety studies have investigated the effects of oxaloacetate on children, pregnant or breastfeeding women. We therefore advise strongly against taking oxaloacetate supplements if you are pregnant or breastfeeding.

Oxaloacetate supplements suffer from a severe lack of reliable research to back up the claims on the bottle.

Many of the reported health benefits have only been studied in cells, worms, or (at best) rodents. Furthermore, in these studies, the cells or animals tend to be either submerged in or injected with oxaloacetate; these results cannot be translated with confidence to oral supplementation.

Human studies are few and far between, and some of them are decades old with outdated methodology. Existing recent studies are small, not particularly powerful, and at high risk of bias. When people recommend oxaloacetate supplements, they often cite a single study the founder of Terra Biological, which manufactures benaGene and Jubilance. His conflict of interest is clear.

Note, again, that oxaloacetate is extremely difficult to stabilize. Researchers have struggled to keep it from spontaneously degrading in animal feed. Neither Terra Biological LLC nor any other company have disclosed their methods for stabilizing oxaloacetate. No oxaloacetate supplement has been independently evaluated by a third party.

Oxaloacetate is a vital part of the body’s energy production machinery. In worms, it extends lifespan, which has made it an interesting target of longevity research. However, few of this compound’s purported benefits have been demonstrated in mammals, let alone humans.

In the human body, oxaloacetate increases the NAD to NADH ratio, which activates other pathways associated with a longer life. It also may “scavenge” glutamate to reduce the risk of brain damage.

However, these effects may only appear with oxaloacetate injections; oral supplements are highly unstable and may not be well absorbed. There are also no significant food sources of oxaloacetate.

The evidence for oxaloacetate’s benefits is sparse and the product is expensive. For each of the potential benefits discussed in this post, better options are available.

This section contains sponsored links, which means that we may receive a small percentage of profit from your purchase, while the price remains the same to you. The proceeds from your purchase support our research and work. Thank you for your support.

About the Author

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

Vitamin B12 is part of the Vitamin B complex. It is considered to be a “Painkilling vitamin”. It helps DNA production, cardiovascular support, and energy metabolism. In this post, learn more about Vitamin B12, its functions, causes of deficiencies, as well as foods and other sources so you can better incorporate B12 into your life.

Vitamin B12 is a very important marker to monitor, especially if you haven’t been leading the best lifestyle or you have known chronic health issues.

Vitamin B12, also referred to as cobalamin, is a water-soluble vitamin [1].

It contributes to the successful synthesis of DNA, the normal functioning of the nervous system, and the production of energy [2].

The liver is the main site of storage of vitamin B12 in the human body [3]. Humans can obtain vitamin B from dietary sources, fortified foods, and supplements [4, 5, 6].

It can take the form of cyano-, hydroxyl, methyl, and deoxy adenosyl-cobalamin [7].

Cyanocobalamin, the most stable and unnatural form of vitamin B12, is most commonly used in supplements and does not have a direct cofactor role in cellular metabolism.

The most biologically significant forms of vitamin B12 are methylcobalamin and coenzyme B12 (5’-deoxy-5’-adenosylcobalamin) [8, 9].

Vitamin B12 was considered the “Painkilling Vitamin” in some countries as far back as the 1950s [10].

The normal range for vitamin B12 is between 200 and 900 nanograms per milliliter (ng/mL).

In this case, however, your lab result may be in the reference range, but not actually be in the optimal range. Vitamin B12 even in the ‘normal’ range can be unhealthy and indicate that certain processes in the body aren’t optimal.

Cobalamin helps break down methylmalonic acid (MMA) [11] and homocysteine – hence, high levels of MMA or homocysteine in the blood may indicate a B12 deficiency. Some studies say this is even a better indicator of B12 status than direct B12 measurement [12].

One study in 94 women found that vitamin B12 levels lower than 250 mg/dL increased risk by 3X the likelihood of having a child with birth defects [13].

Methylcobalamin, a form of Vitamin B12, reduces the clinical symptoms in legs such as paresthesia (an abnormal sensation like tingling or pricking), burning pains, and spontaneous pain [14].

In one study, methylcobalamin significantly improved symptoms, such as pain and prickling sensation, in patients with neck pain [15].

Intramuscular cobalamin injection is effective in alleviating low back pain in patients with no nutritional deficiencies [16].

Cobalamin provides effective pain management for mouth ulcers [17].

Methylcobalamin treatment reduces pain symptoms in neuralgia, diabetic neuropathy, and lower back pain [18, 19, 20].

Methylcobalamin (MeCbl) is the most effectively taken form of vitamin B12 in neuronal organelles [10].

Cobalamin may have a role in the prevention of disorders of brain development and mood disorders as well as Alzheimer’s and vascular dementia in the elderly [23].

Supplementation of cobalamin is useful in neuronal regeneration. It also repairs the negative effects of ischemia on neurons [24].

A study on rats with sciatic nerve injuries supports the treatment of peripheral nerve injuries with Cobalamin [25].

B12 also increases the regeneration of axons and promotes neuronal repair [26, 27, 28].

Cobalamin treatment improves sleep-wake rhythm disorders in human subjects [29, 30].

It may increase the light sensitivity of circadian rhythms due to decreased melatonin levels [31].

It’s not normal to struggle falling asleep and wake up in the morning feeling more tired than when you went to bed. Biohacking Insomnia attacks sleep issues from every angle including limbic system repair, hormone levels, and circadian rhythm retraining.

In a randomized trial performed on patients with depression and low normal cobalamin levels, cobalamin supplementation improved depressive symptoms [32].

Studies have found that prolonged consumption (several weeks to years) may decrease the risk of depression relapse and the onset of clinically significant symptoms in people at risk [33].

Methyl B12 suppresses cytokine production of T lymphocytes in cells and is speculated to do the same in patients with rheumatoid arthritis [34].

Topical cobalamin is a new therapeutic option in atopic dermatitis. It is well-tolerable and has low safety risks for both adults and children [35, 36].

One randomized clinical trial states that oral cobalamin supplementation with 250 μg/day throughout pregnancy and early lactation elevates maternal, fetal, and breast milk vitamin B12 levels [37].

Higher homocysteine and decreased B12 levels have been associated with an increased risk of macular degeneration [38].

One study involved 5,442 women at high risk of cardiovascular disease aged 40 or older, who had been taking B6/B9/B12 for 7 years.

The study found a 34 – 41% decreased risk of macular degeneration when supplementing with B6/B9/B12 may reduce the risk of macular degeneration [39].

B12 (Cobalamin) leads to the production of S-Adenosyl-Methionine SAM, which increases methylation [40, 41, 42, 43, 44].

Only fortified nutritional yeast contains vitamin B12.

Vitamin B12 Deficiencies

The long-term consequences of less severe B12 deficiency are not fully known but may include adverse effects on pregnancy, vascular, cognitive, bone and eye health [54].

Methylcobalamin increases nerve conduction, myelin regeneration, neuron regeneration, and inhibiting pain transmission [21, 10, 22, 10].

B12 deficiency in women is associated with infertility and miscarriage [55].

B12 deficiency causes excess homocysteine, which is a proven risk factor for cardiovascular disease [56]. Individuals with B12 deficiency have a higher prevalence of cardiovascular risk factors such as heart failure, stroke, and diabetes [57].

Deficiency of B12 inhibits melanin transfer between melanocytes and keratinocytes, which may cause darkening of the skin. 19% of subjects in one clinical trial manifested skin darkening resulting from cobalamin deficiency [58, 59].

Vitamin B12 plays an essential role in the production of red blood cells and low red blood cells can indicate a B12 deficiency [60, 61]. Weakness and fatigue can result if your red blood cells are low since you are not getting enough oxygen to tissues.

Since vitamin B12 is important in producing myelin, a deficiency can cause psychiatric and cognitive problems and pins & needles. In one study with 141 patients, 28% of people who had psychiatric symptoms from B12 deficiency didn’t have any signs of anemia [62].

Low levels of B12 have been linked to depression [33] and Alzheimer’s disease and other types of cognitive impairment [63].

Studies have found that prolonged consumption (several weeks to years) may decrease the risk of depression relapse and the onset of clinically significant symptoms in people at risk [33].

B12 deficiency can cause neuropathy or nerve pain [64], either as a result of a lack of oxygen to the nerves or from myelin destruction.

In this study, every patient treated with B12 had an improvement in psychiatric problems (39 of 39). They also improved various blood markers, as well as a 50% decrease in methylmalonic acid and/or homocysteine [62].

In one 7-year-old boy, B12 deficiency from a vegan diet resulted in neurological symptoms [65].

Multiple studies show that B12 deficiency in the elderly can increase the risk of weakness, frailty, and disability, and increase hospital stay [66, 67, 54, 68].

With regard to bone health, multiple studies show that B12 deficiency can increase the risk of bone fracture and is associated with lower bone mass [54, 69].

In 4 people who didn’t have cognitive symptoms or anemia, a swollen and inflamed tongue with lesions was found to be an early sign of vitamin B12 deficiency [70].

Although rare, vitamin B12 deficiency can cause blurred vision or eye pain. This can occur when an untreated B12 deficiency results in damage to the optic nerve [71].

About 6% of people in the US aged 60 or older are clinically vitamin B12 deficient, while about 20% have technically “normal” levels (148 – 221 pmol/L), but are far from optimal [72].

Vitamin B12 deficiency increases with age, from about 1 in 20 among people aged 65 – 74 years to 1 in 10 or even greater among people aged 75 years or greater [67].

• People on a vegan/vegetarian diet
• People with anemia
• Older people
• People with gastrointestinal disorders, such as Crohn’s disease or celiac disease
• Those who have had gastrointestinal surgeries

Pregnant women require higher levels of B12 to prevent birth defects (over 300 mg/dL [13]).

Infants born to B12 deficient mothers or receiving deficient amounts of animal-sourced foods are susceptible to deficiency between the ages of 6 – 12 months [74].

Patients with type 2 diabetes who are prescribed Metformin may be at risk for cobalamin deficiency [75].

Proton pump inhibitors or Histamine 2 receptor blockers (Zantac, Tagamet) may lead to b12 deficiency, as a result of poorer B12 absorption [76, 77].

Hormonal birth control (oral contraception and DMPA) usage among female subjects reduced B12 levels [78].

Genes (notably TCN2) related to B12 deficiency are associated with autoimmune gastritis [79].

This section contains sponsored links, which means that we may receive a small percentage of profit from your purchase, while the price remains the same to you. The proceeds from your purchase support our research and work. Thank you for your support.

About the Author

Joe Cohen won the genetic lottery of bad genes. As a kid, he suffered from inflammation, brain fog, fatigue, digestive problems, anxiety, depression, and other issues that were poorly understood in both conventional and alternative medicine.Frustrated by the lack of good information and tools, Joe decided to embark on a journey of self-experimentation and self-learning to improve his health--something that has since become known as “biohacking”. With thousands of experiments and pubmed articles under his belt, Joe founded SelfHacked, the resource that was missing when he needed it. SelfHacked now gets millions of monthly readers.Joe is a thriving entrepreneur, author and speaker. He is the CEO of SelfHacked, SelfDecode and LabTestAnalyzer.His mission is to help people gain access to the most up-to-date, unbiased, and science-based ways to optimize their health.

Joe has been studying health sciences for 17 years and has read over 30,000 PubMed articles. He's given consultations to over 1000 people who have sought his health advice. After completing the pre-med requirements at university, he founded SelfHacked because he wanted to make a big impact in improving global health. He's written hundreds of science posts, multiple books on improving health, and speaks at various health conferences. He's keen on building a brain-trust of top scientists who will improve the level of accuracy of health content on the web. He's also founded SelfDecode and LabTestAnalyzer, popular genetic and lab software tools to improve health.

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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