What organ processes vitamin B?
Vitamins are organic compounds found in very small amounts in food and required for normal functioning—indeed, for survival. Humans are able to synthesize certain vitamins to some extent. For example, vitamin D is produced when the skin is exposed to sunlight; niacin can be synthesized from the amino acid tryptophan; and vitamin K and biotin are synthesized by bacteria living in the gut. However, in general, humans depend on their diet to supply vitamins. When a vitamin is in short supply or is not able to be utilized properly, a specific deficiency syndrome results. When the deficient vitamin is resupplied before irreversible damage occurs, the signs and symptoms are reversed. The amounts of vitamins in foods and the amounts required on a daily basis are measured in milligrams and micrograms.
Unlike the macronutrients, vitamins do not serve as an energy source for the body or provide raw materials for tissue building. Rather, they assist in energy-yielding reactions and facilitate metabolic and physiologic processes throughout the body. Vitamin A, for example, is required for embryonic development, growth, reproduction, proper immune function, and the integrity of epithelial cells, in addition to its role in vision. The B vitamins function as coenzymes that assist in energy metabolism; folic acid (folate), one of the B vitamins, helps protect against birth defects in the early stages of pregnancy. Vitamin C plays a role in building connective tissue as well as being an antioxidant that helps protect against damage by reactive molecules (free radicals). Now considered to be a hormone, vitamin D is involved in calcium and phosphorus homeostasis and bone metabolism. Vitamin E, another antioxidant, protects against free radical damage in lipid systems, and vitamin K plays a key role in blood clotting. Although vitamins are often discussed individually, many of their functions are interrelated, and a deficiency of one can influence the function of another.
Vitamin nomenclature is somewhat complex, with chemical names gradually replacing the original letter designations created in the era of vitamin discovery during the first half of the 20th century. Nomenclature is further complicated by the recognition that vitamins are parts of families with, in some cases, multiple active forms. Some vitamins are found in foods in precursor forms that must be activated in the body before they can properly fulfill their function. For example, beta(β)- carotene, found in plants, is converted to vitamin A in the body.
The 13 vitamins known to be required by human beings are categorized into two groups according to their solubility. The four fat-soluble vitamins (soluble in nonpolar solvents) are vitamins A, D, E, and K. Although now known to behave as a hormone, the activated form of vitamin D, vitamin D hormone (calcitriol), is still grouped with the vitamins as well. The nine water-soluble vitamins (soluble in polar solvents) are vitamin C and the eight B-complex vitamins: thiamin, riboflavin, niacin, vitamin B6, folic acid, vitamin B12, pantothenic acid, and biotin. Choline is a vitamin-like dietary component that is clearly required for normal metabolism but that can be synthesized by the body. Although choline may be necessary in the diet of premature infants and possibly of those with certain medical conditions, it has not been established as essential in the human diet throughout life.
Different vitamins are more or less susceptible to destruction by environmental conditions and chemical agents. For example, thiamin is especially vulnerable to prolonged heating, riboflavin to ultraviolet or fluorescent light, and vitamin C to oxidation (as when a piece of fruit is cut open and the vitamin is exposed to air). In general, water-soluble vitamins are more easily destroyed during cooking than are fat-soluble vitamins.
The solubility of a vitamin influences the way it is absorbed, transported, stored, and excreted by the body as well as where it is found in foods. With the exception of vitamin B12, which is supplied by only foods of animal origin, the water-soluble vitamins are synthesized by plants and found in both plant and animal foods. Strict vegetarians (vegans), who eat no foods of animal origin, are therefore at risk of vitamin B12 deficiency. Fat-soluble vitamins, on the other hand, are found in association with fats and oils in foods and in the body and typically require protein carriers for transport through the water-filled compartments of the body.
Water-soluble vitamins are not appreciably stored in the body (except for vitamin B12) and thus must be consumed regularly in the diet. If taken in excess they are readily excreted in the urine, although there is potential toxicity even with water-soluble vitamins; especially noteworthy in this regard is vitamin B6. Because fat-soluble vitamins are stored in the liver and fatty tissue, they do not necessarily have to be taken in daily, so long as average intakes over time—weeks, months, or even years—meet the body’s needs. However, the fact that these vitamins can be stored increases the possibility of toxicity if very large doses are taken. This is particularly of concern with vitamins A and D, which can be toxic if taken in excess. Under certain circumstances, pharmacological (“ megadose”) levels of some vitamins—many times higher than the amount typically found in food—have accepted medical uses. Niacin, for example, is used to lower blood cholesterol levels; vitamin D is used to treat psoriasis; and pharmacological derivatives of vitamin A are used to treat acne and other skin conditions as well as to diminish skin wrinkling. However, consumption of vitamins or other dietary supplements in amounts significantly in excess of recommended levels is not advised without medical supervision.
Vitamins synthesized in the laboratory are the same molecules as those extracted from food, and they cannot be distinguished by the body. However, various forms of a vitamin are not necessarily equivalent. In the particular case of vitamin E, supplements labeled d-α-tocopherol (or “natural”) generally contain more vitamin E activity than those labeled dl-α-tocopherol. Vitamins in food have a distinct advantage over vitamins in supplement form because they come associated with other substances that may be beneficial, and there is also less potential for toxicity. Nutritional supplements cannot substitute for a healthful diet.
Unlike the complex organic compounds (carbohydrates, lipids, proteins, vitamins) discussed in previous sections, minerals are simple inorganic elements—often in the form of salts in the body—that are not themselves metabolized, nor are they a source of energy. Minerals constitute about 4 to 6 percent of body weight—about one-half as calcium and one-quarter as phosphorus (phosphates), the remainder being made up of the other essential minerals that must be derived from the diet. Minerals not only impart hardness to bones and teeth but also function broadly in metabolism—e.g., as electrolytes controlling the movement of water in and out of cells, as components of enzyme systems, and as constituents of many organic molecules.
As nutrients, minerals are traditionally divided into two groups according to the amounts present in and needed by the body. The major minerals ( macrominerals)—those required in amounts of 100 milligrams or more per day—are calcium, phosphorus (phosphates), magnesium, sulfur, sodium, chloride, and potassium. The trace elements (microminerals or trace minerals), required in much smaller amounts of about 15 milligrams per day or less, include iron, zinc, copper, manganese, iodine (iodide), selenium, fluoride, molybdenum, chromium, and cobalt (as part of the vitamin B12 molecule). Fluoride is considered a beneficial nutrient because of its role in protecting against dental caries, although an essential function in the strict sense has not been established in human nutrition.
The term ultratrace elements is sometimes used to describe minerals that are found in the diet in extremely small quantities (micrograms each day) and are present in human tissue as well; these include arsenic, boron, nickel, silicon, and vanadium. Despite demonstrated roles in experimental animals, the exact function of these and other ultratrace elements (e.g., tin, lithium, aluminum) in human tissues and indeed their importance for human health are uncertain.
Minerals have diverse functions, including muscle contraction, nerve transmission, blood clotting, immunity, the maintenance of blood pressure, and growth and development. The major minerals, with the exception of sulfur, typically occur in the body in ionic (charged) form: sodium, potassium, magnesium, and calcium as positive ions ( cations) and chloride and phosphates as negative ions ( anions). Mineral salts dissolved in body fluids help regulate fluid balance, osmotic pressure, and acid-base balance.
Sulfur, too, has important functions in ionic forms (such as sulfate), but much of the body’s sulfur is nonionic, serving as an integral part of certain organic molecules, such as the B vitamins thiamin, biotin, and pantothenic acid and the amino acids methionine, cysteine, and cystine. Other mineral elements that are constituents of organic compounds include iron, which is part of hemoglobin (the oxygen-carrying protein in red blood cells), and iodine, a component of thyroid hormones, which help regulate body metabolism. Additionally, phosphate groups are found in many organic molecules, such as phospholipids in cell membranes, genetic material (DNA and RNA), and the high-energy molecule adenosine triphosphate (ATP).
The levels of different minerals in foods are influenced by growing conditions (e.g., soil and water composition) as well as by how the food is processed. Minerals are not destroyed during food preparation; in fact, a food can be burned completely and the minerals (ash) will remain unchanged. However, minerals can be lost by leaching into cooking water that is subsequently discarded.
Many factors influence mineral absorption and thus availability to the body. In general, minerals are better absorbed from animal foods than from plant foods. The latter contain fibre and other substances that interfere with absorption. Phytic acid, found principally in cereal grains and legumes, can form complexes with some minerals and make them insoluble and thereby indigestible. Only a small percentage of the calcium in spinach is absorbed because spinach also contains large amounts of oxalic acid, which binds calcium. Some minerals, particularly those of a similar size and charge, compete with each other for absorption. For example, iron supplementation may reduce zinc absorption, while excessive intakes of zinc can interfere with copper absorption. On the other hand, the absorption of iron from plants ( nonheme iron) is enhanced when vitamin C is simultaneously present in the diet, and calcium absorption is improved by adequate amounts of vitamin D. Another key factor that influences mineral absorption is the physiological need for the mineral at the time.
Unlike many vitamins, which have a broader safety range, minerals can be toxic if taken in doses not far above recommended levels. This is particularly true for the trace elements, such as iron and copper. Accidental ingestion of iron supplements has been a major cause of fatal poisoning in young children.
Although often overlooked as a nutrient, water (H2O) is actually the most critical nutrient of all. Humans can survive weeks without food but only a matter of days without water.
Water provides the medium in which nutrients and waste products are transported throughout the body and the myriad biochemical reactions of metabolism occur. Water allows for temperature regulation, the maintenance of blood pressure and blood volume, the structure of large molecules, and the rigidity of body tissues. It also acts as a solvent, a lubricant (as in joints), and a protective cushion (as inside the eyes and in spinal fluid and amniotic fluid). The flow of water in and out of cells is precisely controlled by shifting electrolyte concentrations on either side of the cell membrane. Potassium, magnesium, phosphate, and sulfate are primarily intracellular electrolytes; sodium and chloride are major extracellular ones.
Water makes up about 50 to 70 percent of body weight, approximately 60 percent in healthy adults and an even higher percentage in children. Because lean tissue is about three-quarters water, and fatty tissue is only about one-fifth water, body composition—the amount of fat in particular—determines the percentage of body water. In general, men have more lean tissue than women, and therefore a higher percentage of their body weight is water.
Water is consumed not only as water itself and as a constituent of other beverages but also as a major component of many foods, particularly fruits and vegetables, which may contain from 85 to 95 percent water. Water also is manufactured in the body as an end product of metabolism. About 2.5 litres (about 2.6 quarts) of water are turned over daily, with water excretion (primarily in urine, water vapour from lungs, sweat loss from skin, and feces) balancing intake from all sources. Because water requirements vary with climate, level of activity, dietary composition, and other factors, there is no one recommendation for daily water intake. However, adults typically need at least 2 litres (8 cups) of water a day, from all sources. Thirst is not reliable as a register for dehydration, which typically occurs before the body is prompted to replace fluid. Therefore, water intake is advised throughout the day, especially with increased sweat loss in hot climates or during vigorous physical activity, during illness, or in a dehydrating situation such as an airplane flight.
Vitamin B12 Deficiency
Vitamin B12 deficiency is one of the most prevalent nutritional deficiencies. It causes a range of symptoms, eg fatigue, forgetfulness, and tingling of the hands and feet.
The reason for the wide variety of symptoms is that vitamin B12 plays a principal role in numerous body functions eg
- Essential for DNA synthesis. DNA (central information storage system of most animals, plants, and even some viruses), directs proper formation of every part of the body.
- Vitamin B12 deficiency increases homocysteine levels (normally degraded by vitimain B 12) which causes inflammation and toxic damage to the body. Elevated homocysteine increases your risks for dementia, heart disease and stroke, as it . 
Vitamin B12 Uptake [ edit | edit source ]
Vitamin B12 is bound to protein in food and must be released before it is absorbed. The process starts in the mouth when food is mixed with saliva. The freed vitamin B12 then binds with haptocorrin (protects acid sensitive B12 as it moves through the stomach). In the duodenum, digestive enzymes free the vitamin B12 from haptocorrin, and this freed vitamin B12 combines with intrinsic factor, a transport and delivery binding protein secreted by the stomach’s parietal (lining) cells. The resulting complex is absorbed in the distal ileum by receptor-mediated endocytosis. If vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and therefore does not require the separation step  .
Etiology [ edit | edit source ]
Causes of vitamin B12 deficiency include:
- Difficulty absorbing vitamin B12 from food, eg any patient with a history of gastric bypass surgery may be at risk; surgical resection terminal ileum due to eg Crohn’s disease; damage to the small intestine, eg inflammation from celiac disease or infection with the tapeworm.
- Autoimmune: Pernicious anemia is an autoimmune condition in which antibodies to intrinsic factor are produced. Anti-intrinsic factor antibodies bind to and inhibit the effects of intrinsic factor, resulting in an inability of B12 to be absorbed by the terminal ileum.
- Prolonged use of certain medications e.g. metformin, proton pump inhibitors.
- Dietary Insufficiency: Vitamin B12 is stored in excess in the liver; however, patients who have followed a strict vegan diet for approximately three years may develop a B12 deficiency from a lack of dietary intake  .
Risk Factors [ edit | edit source ]
The following groups are among those most likely to be vitamin B12 deficient.
- Older adults: Between 3% and 43% of community-dwelling older adults, especially those with atrophic gastritis (an autoimmune condition) have vitamin B12 deficiency.
- Conditions associated with vitamin B12 inadequacy include: pernicious anemia; Atrophic gastritis, affects 8–9% of adults aged 65 and older; Helicobacter pylori infection, inflammation leads to malabsorption of vitamin B12 from food.
- Individuals with gastrointestinal disorders or who have had gastrointestinal surgery
- Vegetarians and Infants of vegan women
The below video gives a good summary of the condition
Characteristics/Clinical Presentation [ edit | edit source ]
Fatigue a common sign in many diseases
The most common sign of vitamin B12 deficiency is Fatigue. This is caused by the lack of red blood cells to carry oxygen to body tissue.
Lack of red blood cells may also cause:
- Shortness of breath
- Coldness in your hands and feet,
- Pale or yellowish skin
- Chest pain
- Sensory and Motor Impairments
- Loss of appetite and Weight loss
- Loss of Balance
- Depression and Confusion
- Poor Memory
- Dementia or Cognitive changes
- Soreness of mouth 
Treatment [ edit | edit source ]
Vitamin B12 deficiency can be managed with supplemental B12. This could be an oral supplement or an injection. If B12 deficiency is caused by a problem with absorption, an injection of B12 will help the vitamin to be absorbed directly into the body.
Some patients need lifelong B12 supplementation. This usually depends on the cause of the deficiency, possibly with the need to continue taking B12 supplements even after symptoms have improved.
Recovery from vitamin B12 deficiency takes time. Improvement may be gradual and may continue for up to six to 12 months  .
Systemic Involvement [ edit | edit source ]
Vitamin B12 deficiency can cause haematologic, neurologic, gastrointestinal, and cardiovascular symptoms.
- Haematologic — Hematologic pathology may cause the following symptoms: skin pallor, weakness, fatigue, syncope, shortness of breath, and palpitations.
- Neurological — The most common neurological symptom is tingling in the hands and feet. Other possible neurological symptoms that could occur: paresthesia, weakness, motor deficits, loss of vision, behavioural changes, and cognitive changes.
- Gastrointestinal — Gastrointestinal dysfunction can cause symptoms such as anorexia, flatulence, diarrhoea, and constipation.
- Cardiovascular — Vitamin B12 deficiency can lead to increased risk of coronary artery disease and stroke. Vitamin B12 deficiency causes hyperhomocysteinemia which can increase occlusions in the vascular system. There is not a lot of evidence to prove that vitamin B12 will cause vascular issues, but the evidence does link the two together. 
Physical Therapy Management [ edit | edit source ]
An individual with a confirmed or suspected Vitamin B12 deficiency is typically treated by a primary physician with mediation that includes intramuscular injection, oral Vitamin B12 supplements, or through a change in nutritional habits. Treating or diagnosing a patient with a vitamin deficiency typically falls outside of the Physical Therapist Scope of Practice, however physical therapists should be aware of the presenting sign and symptoms of Vitamin B12 deficiency and refer to proper medical personnel with any unusual findings. Physical Therapists should be particularly familiar with the role Vitamin B12 on the nervous system.
- If a physical therapist suspects that a Vitamin B12 deficiency may be present they should refer to MD.
- Early diagnosis of the deficiency is extremely important because the effect of treatments is believed to be linked to the time of diagnosis  .
Vitamin B12 and the Nervous System [ edit | edit source ]
Deficit of B12; Spinal cord MRI degeneration posterior columns.
Vitamin B12 acts as a co-enzyme that facilitates myelin synthesis. A defect in the myelin synthesis can lead to both central and peripheral nerve function abnormalities. Some conditions seen with this dysfunction include: myelopathy, neuropathy and optic nerve atrophy. Roughly 25% of individuals suffering from a vitamin B12 deficiency experience peripheral neuropathy.
The spinal cord can become involved in severe deficiency and a syndrome often seen with this is sub-acute combined degeneration (SCD). MRI findings may reveal an inflammation of the spinal cord, most commonly reported at the T2 level.  Clinical presentations of SCD include  
- Bilateral sensory deficits most commonly affecting bilateral lower extremities
- Bilateral lower extremity weakness
- Decreased proprioception and vibration sensation
- Positive Rombergs Sign
- Abnormal reflexes
- Spastic paresis
For an image of MRI showing image of see SCD:
Dietary Management [ edit | edit source ]
The most common way to treat vitamin B12 deficiency alternatively is through increasing dietary intake.
Vitamin B12 is a nutrient that is only found in animal products such as meat, chicken, fish, eggs, and dairy. Therefore vegans are at especially high risk of low nutritional vitamin B12, as are non-vegan individuals who do not eat enough of these vitamin B12 rich foods.
Some foods are fortified with vitamin B12, vegans have to make an effort to seek out those types of foods. 
Food Sources containing vitamin B12, in descending order
Per Serving/Percent of Daily Values
Liver, beef, cooked, 3 ounces
Breakfast cereals, fortified with 100% of the DV for vitamin B12, 1 serving
Trout, rainbow, wild, cooked, 3 ounces
Salmon, sockeye, cooked, 3 ounces
Trout, rainbow, farmed, cooked, 3 ounces
Tuna fish, light, canned in water, 3 ounces
Cheeseburger, double patty and bun, 1 sandwich
Haddock, cooked, 3 ounces
Breakfast cereals, fortified with 25% of the DV for vitamin B12, 1 serving
Beef, top sirloin, broiled, 3 ounces
Yogurt, fruit, low-fat, 8 ounces
Cheese, Swiss, 1 ounce
Beef taco, 1 soft taco
Ham, cured, roasted, 3 ounces
Egg, whole, hard boiled, 1 large
Chicken, breast meat, roasted, 3 ounces
Pernicious anemia, one of the causes of vitamin B12 deficiency, is an autoimmune condition that prevents your body from absorbing vitamin B12. Left untreated, pernicious anemia can cause serious medical issues, including irreversible damage to your nervous system.
What is pernicious anemia?
Pernicious (per-nish-uhs) anemia, one of the causes of vitamin B12 deficiency, is an autoimmune condition that prevents your body from absorbing vitamin B12. Without adequate vitamin B12, you have fewer red blood cells carrying oxygen throughout your body. You can have pernicious anemia for several years before noticing changes in your body. Left untreated, pernicious anemia can cause serious medical issues, including irreversible damage to your nervous system. Healthcare providers treat pernicious anemia by prescribing vitamin B12 supplements.
How does pernicious anemia affect my body?
The term “pernicious” means harmful, and pernicious anemia causes harm to several body systems:
- Digestive system problems that cause nausea, bloating and weight loss.
- Nervous system damage that causes muscle weakness, numbness or tingling in your hands and feet, memory loss and dementia.
- Heart problems that can cause palpitations (feeling as your heart is beating too fast or skipping beats).
- Weakness and fatigue.
Who is affected by pernicious anemia?
Pernicious anemia typically affects people aged 60 to 80 of Northern European descent. Pernicious anemia is estimated to affect 151 in 100,000 people in the United States.
Symptoms and Causes
What are pernicious anemia symptoms?
Generally speaking, the longer you go without adequate vitamin B12, the more serious your symptoms are. Early on, people may have mild symptoms they may think are caused by other common conditions. Examples include:
- Diarrhea or constipation.
- Lightheadedness when standing up or with exertion.
- Loss of appetite.
- Pale skin (mild jaundice or yellowing of your eyes or skin).
- Shortness of breath (dyspnea), mostly during exercise.
- Swollen, red tongue or bleeding gums.
What are examples of pernicious anemia symptoms caused by long-term low vitamin B12 levels?
Long-term low vitamin B12 levels caused by pernicious anemia can affect your nervous system. Symptoms of potential nervous system problems include:
- Short-term memory loss.
- Loss of balance.
- Numbness and tingling in your hands and feet.
- Problems concentrating.
- Optic nerve degeneration that affects your eyesight.
Can I have pernicious anemia without having symptoms?
Yes. Normally, your body stores vitamin B12 that it gets from what you eat. Your body stores vitamin B 12, slowly using it over time. It can take three to five years for your body to use up your vitamin B12 reserves. After that, it can be several more years before you develop pernicious anemia symptoms.
What causes pernicious anemia?
Pernicious anemia is an autoimmune condition that happens when your immune system produces antibodies that attack cells in the mucosal lining of your stomach and nerve cells. Your immune system’s response affects your body’s ability to absorb vitamin B12.
The antibodies also block a critical protein called intrinsic (in-TRIN-sic) factor. Normally, intrinsic factor carries the vitamin B12 we get from food to special cells in your small intestine. From there, the vitamin B12 is transported into your bloodstream. Other proteins then carry the vitamin B12 to your bone marrow, where the vitamin is used to make new red blood cells. This process can’t happen when your immune system blocks your intrinsic factor.
You may also develop vitamin B12 deficiency if:
- You have surgery to remove part or all of your stomach, which eliminates the cells that enable vitamin B12 absorption. About half of people who have gastric bypass surgery to treat obesity lose cells that enable vitamin B12 absorption.
- Part or all of your small intestine is surgically removed, reducing your small intestine’s ability to absorb vitamin B12.
- You have Small Intestine Bacterial Overgrowth (SIBO). SIBO happens when you have too many of the wrong kind of bacteria in your small intestine. This bacteria often uses up any vitamin B12 before your small intestine can absorb the vitamin.
- You take some medications, including antibiotics for infections and medicines for diabetes and seizures, which affect vitamin B12 levels.
- You have a tapeworm infection. You can get a tapeworm infection by eating infected fish that was undercooked. Tapeworms feed on vitamin B12.
- You follow a vegan or vegetarian diet that doesn’t include enough vitamin B12.
- You have medical conditions that affect your digestive system like celiac disease or Crohn’s disease that make it hard for your body to absorb enough vitamin B12.
- You have endocrine autoimmune diseases, such as hypoparathyroidism and Graves’ disease, that increase your risk for developing pernicious anemia.
Diagnosis and Tests
How is pernicious anemia diagnosed?
First, your healthcare provider will complete a thorough physical examination and ask questions about your medical history so they know if you’ve any other conditions that may increase your risk of vitamin B12 deficiency. They may ask you if you’re having trouble concentrating. They may look for signs of nervous system problems. Other tests they may do include:
- Vitamin B12 level.
- Complete blood count (CBC): This blood test determines the type of anemia you have and the degree of your anemia.
- Reticulocyte count: This test indicates if your bone marrow can make new red blood cells.
- Lactate dehydrogenase (LDH) levels: LDH is an enzyme that many cells make. Extremely high LDH levels may indicate pernicious anemia.
- Serum bilirubin levels.
- Methylmalonic acid (MMA) levels: High MMA levels confirm vitamin B12 deficiency.
- Homocysteine level: High homocysteine levels may be a sign of vitamin B12 deficiency. Tests for the presence of the antibodies that attack the parietal cells in your stomach and block the action of intrinsic factor.
- Upper endoscopy: Healthcare providers use a thin, tube-like instrument with a light and lens for viewing called an endoscope to look for signs of degeneration or atrophy (wasting away) of the lining of your stomach.
Management and Treatment
How is pernicious anemia treated?
Since vitamin B12 absorption is blocked, your healthcare provider may prescribe intramuscular vitamin B12 injections. Later, after B12 stores are back to normal, they may prescribe high doses of oral B12 replacement. They’ll monitor your treatment. They may prescribe antibiotics if you have bacteria in your intestine that prevents your body from absorbing vitamin B12.
How soon after treatment will I feel better?
Many people begin feeling better a few days after starting treatment. But you may need a few weeks of regular treatment before you notice significant changes and your condition improves.
Will I always need vitamin B12 treatments or supplements?
Everyone’s situation is different, but most people who have pernicious anemia take vitamin B12 supplements for the rest of their lives.