What is carotenemia

Carotenemia is the term used for increased beta-carotene levels in the blood and yellow pigmentation of the skin. Strictly speaking, excessive carotene in the skin should be called carotenoderma. The terms xanthoderma (yellow skin) and carotenosis are also used. In most cases, carotenemia follows prolonged and excessive consumption of carotene-rich foods, such as carrots, squash, and sweet potatoes. Carotenemia is a common finding in children. Carotenemia is usually harmless, but it can lead to a mistaken diagnosis of jaundice.

Carotenemia is more easily appreciated in light-complexioned people, and may present chiefly as yellowing of the palms and the soles in more darkly pigmented individuals.

Carotenoids are yellow colored, lipid-soluble compounds found in red, orange, yellow and green vegetables and fruit. They include:

• alpha- and beta carotene
• lycopene (red colour in tomatoes)
• beta-cryptoxanthin
• lutein
• canthazanthin
• astaxanthin
• zeaxanthin.

By far the most important provitamin A carotenoid is beta-carotene; other provitamin A carotenoids are alpha-carotene and beta-cryptoxanthin. The body converts these plant pigments into vitamin A. Both provitamin A and preformed vitamin A must be metabolized intracellularly to retinal and retinoic acid, the active forms of vitamin A, to support the vitamin’s important biological functions ¹. Other carotenoids found in food, such as lycopene, lutein, and zeaxanthin, are not converted into vitamin A.

Carotenoids are a normal part of our diet and contribute to the normal color of your skin. They also help protect your skin from sunburn.

Carotenoids are precursors of an essential vitamin, Vitamin A or retinol. Conversion takes place in the mucosal cells that line the small intestine and in the liver. Pancreatic lipase enzymes, bile salts, fat, and thyroid hormone aid conversion of carotenoids to vitamin A. Carotenoids are cleared from the body in sweat, sebum, urine and feces.

Carotenemia can occur at any age but is most common in young children fed large amounts of commercial infant food preparations. These foods often contain carrots, pumpkin, squash, spinach and sweet potato, all of which are high in carotene. Cooking, mashing and pureeing these foods make carotene more available for absorption. carotenemia has also been found in vegetarians or food faddists who over-indulge in carrots and oranges.

Although mostly safe, excessive ingestion of the carotenoid canthaxanthin has been associated with yellow deposits on the retina, visual defects and other adverse effects.

Recommended intakes of vitamin A

Intake recommendations for vitamin A and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board at the Institute of Medicine of the National Academies (formerly National Academy of Sciences) ². Dietary Reference Intake (DRI) is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and gender, include:

• Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.
• Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an recommended dietary allowance (RDA).
• Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals.
• Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects.

Recommended Dietary Allowances (RDAs) for vitamin A are given as mcg of retinol activity equivalents (RAE) to account for the different bioactivities of retinol and provitamin A carotenoids (see Table 1). Because the body converts all dietary sources of vitamin A into retinol, 1 mcg of physiologically available retinol is equivalent to the following amounts from dietary sources: 1 mcg of retinol, 12 mcg of beta-carotene, and 24 mcg of alpha-carotene or beta-cryptoxanthin. From dietary supplements, the body converts 2 mcg of beta-carotene to 1 mcg of retinol.

Currently, vitamin A is listed on food and supplement labels in international units (IUs) even though nutrition scientists rarely use this measure. Conversion rates between mcg RAE and IU are as follows ³:

• 1 IU retinol = 0.3 mcg RAE
• 1 IU beta-carotene from dietary supplements = 0.15 mcg RAE
• 1 IU beta-carotene from food = 0.05 mcg RAE
• 1 IU alpha-carotene or beta-cryptoxanthin = 0.025 mcg RAE

However, under FDA’s new labeling regulations for foods and dietary supplements that take effect by January 1, 2020 (for companies with annual sales of $10 million or more) or January 1, 2021 (for smaller companies), vitamin A will be listed only in mcg retinol activity equivalents (RAE) and not IUs ⁴.

An RAE cannot be directly converted into an IU without knowing the source(s) of vitamin A. For example, the RDA of 900 mcg retinol activity equivalents (RAE) for adolescent and adult men is equivalent to 3,000 IU if the food or supplement source is preformed vitamin A (retinol). However, this RDA is also equivalent to 6,000 IU of beta-carotene from supplements, 18,000 IU of beta-carotene from food, or 36,000 IU of alpha-carotene or beta-cryptoxanthin from food. So a mixed diet containing 900 mcg retinol activity equivalents (RAE) provides between 3,000 and 36,000 IU of vitamin A, depending on the foods consumed.

Table 1. Recommended Dietary Allowances (RDAs) for Vitamin A

Age	Male	Female	Pregnancy	Lactation
0–6 months*	400 mcg RAE	400 mcg RAE
7–12 months*	500 mcg RAE	500 mcg RAE
1–3 years	300 mcg RAE	300 mcg RAE
4–8 years	400 mcg RAE	400 mcg RAE
9–13 years	600 mcg RAE	600 mcg RAE
14–18 years	900 mcg RAE	700 mcg RAE	750 mcg RAE	1,200 mcg RAE
19–50 years	900 mcg RAE	700 mcg RAE	770 mcg RAE	1,300 mcg RAE
51+ years	900 mcg RAE	700 mcg RAE

Footnote: * Adequate Intake (AI), equivalent to the mean intake of vitamin A in healthy, breastfed infants.

[Source ⁵ ]

What causes carotenemia?

A history of excessive carotene intake consistent with the diagnosis of hypercarotenemia is usually present.

Metabolic carotenemia without a history of excessive carotene intake may be due to a genetic defect in the metabolism of carotenoids.

As previously mentioned, amenorrhea may be associated with carotenemia. This occurs in patients who consume a pure or predominantly vegetarian diet without red meat. Dietary modifications can reduce carotene levels, which, in turn, normalize the menstrual cycle.

Patients may present with symptoms—such as pruritus, fatigue, abdominal pain, and weight loss—specific to one of the rare causes of carotenemia.

Carotenemia is usually due to excessive intake of carrots, pumpkin and/or other yellow and green vegetables and citrus fruits. It can also be due to taking nutritional supplements. This is called primary carotenemia and appears several weeks after increased ingestion of the responsible foods.

Carotenemia with normal intake of carotenoids can however be a sign of underlying illness. This is secondary carotenemia. Examples include:

• increased blood fats (hyperlipidaemia), which bind the carotenoids preventing their excretion
• liver disease, hypothyroidism and diabetes mellitus, which impair the conversion of carotenoids to retinol.
• nephrotic syndrome, which prevents excretion of carotenoids in the urine

In rare cases, a genetic defect in carotene metabolism may also result in carotenemia, even when the intake of carotene is normal.

Dietary sources

Diet-induced carotenemia is observed most frequently in infants and young children ⁶. Mothers may induce the condition by giving their infants large amounts of carrots in commercial infant food preparations ⁷.

In addition, vegetarians are more likely to develop carotenemia than nonvegetarians. The condition may also be associated with the ingestion of carotene-rich nutritional supplements ⁸.

The health benefits of foods that contain retinoids may encourage their excessive intake, whether for the foods’ antioxidant vitamins ⁹ or to stimulate T cells ¹⁰. The consumption of fresh fruits and vegetables, such as carrots, may be beneficial to patients with psoriasis and porphyria because of their high content of carotenoids ¹¹.

Carotenes occur in all pigmented fruits and vegetables, being synthesized as they ripen. In green vegetables, the color of carotene is often masked by the green color of chlorophyll. As a rule of thumb, the deeper the green or yellow of a fruit or vegetable, the more carotene it contains. Although often overlooked by parents, most strained baby foods on the market contain carrots. Ingestion of nutrient supplements is another source of carotenemia.

Human and cow milk also contain carotene. The occasional yellow color of milk is due to carotene content, and human milk provides a rich source of carotene, especially if maternal serum carotene levels are high. The yellow color of colostrum is caused by carotene content.

Diseases-related sources

Diseases, including hypothyroidism ¹², diabetes mellitus ¹³, hepatic disorders, anorexia nervosa, and renal diseases, may also give rise to carotenemia ¹⁴.

Diabetes mellitus

Many individuals with diabetes have elevated serum carotene levels, but only 10% of these individuals exhibit yellowing of the skin. Carotenemia may be related to restricted dietary habits, hyperlipidemia, or a deficiency in the conversion of carotene into vitamin A by the liver.

Hypothyroidism

The commonly accepted cause of carotenemia in hypothyroidism is a decrease in the conversion of carotene into vitamin A, as well as associated hyperlipidemia and hypercholesterolemia.

Thyroid hormone is antagonistic to vitamin A and controls its rate of consumption. In hypothyroidism, the consumption of vitamin A is decelerated, and the rate of conversion from carotene to vitamin A is reduced.

Anorexia nervosa

The association between carotenemia and anorexia nervosa is well documented. Carotenemia in patients with this disease is not thought to be associated with a high-carotene diet. It may instead be related to hypercholesterolemia, which is an occasional, albeit reversible, defect in the conversion of carotene to vitamin A, or it may result from a normal intake of dietary carotene in the presence of a decreased requirement.

Systemic amyloidosis

Systemic lambda-type AL amyloidosis may be associated with hyper–β-carotenemia with a prominent carotenoderma facilitating recognition of the diagnosis ¹⁵.

Other

Disorders associated with the development of carotenemia also include the following:

• Liver disease – Primary hepatic injury may prevent the conversion of carotene to vitamin A
• Kidney disease – Serum carotene levels may be markedly elevated in patients with chronic glomerulonephritis and nephrotic syndrome
• Inborn errors of metabolism – Carotenemia may result from a failure to convert carotene into vitamin A due to an inborn error of metabolism
• Familial conditions

Carotenemia symptoms

Carotenemia is characterized by yellow discoloration of the skin (carotenoderma, xanthoderma), particularly in areas where the horny layer is thickened such as the soles and palms. The yellow colour is also most evident on areas where subcutaneous fat is abundant.

The sclera (white outer coating of the eyeball) and mucous membranes (eyes, mouth, nostrils etc) are unaffected by carotenemia – the presence of yellow sclera usually means there is increased circulating bilirubin and is known as jaundice.

Serum beta-carotene levels are usually elevated by 3-4 times the normal level in a patient with visible carotenemia. Vitamin A levels should remain normal but are sometimes slightly high. Liver function tests should remain normal in primary carotenemia.

Carotenemia treatment

The skin color can return to normal with dietary modification. Patients should be advised what foods contain carotene and advised not to overeat these foods. Even though serum levels of carotene may return back to normal soon after restricting carotene intake, the yellow color of the skin may persist for a few months due to accumulated carotene in tissues.

Beta-carotene is an antioxidant and is sometimes used to treat photosensitivity disorders such as polymorphous light eruption and erythropoietic protoporphyria. However its use has not been supported by controlled clinical trials, nor has it been found to reduce the risk of sunburn or to prevent skin cancer.

Carotenemia foods to avoid

Concentrations of preformed vitamin A are highest in liver and fish oils ¹. Other sources of preformed vitamin A are milk and eggs, which also include some provitamin A ¹. Most dietary provitamin A comes from leafy green vegetables, orange and yellow vegetables, tomato products, fruits, and some vegetable oils ¹. The top food sources of vitamin A in the U.S. diet include dairy products, liver, fish, and fortified cereals; the top sources of provitamin A include carrots, broccoli, cantaloupe, and squash ¹⁶.

The U.S. Department of Agriculture’s (USDA’s) Food Data Central lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin A in IUs arranged by nutrient content (https://ods.od.nih.gov/pubs/usdandb/VitaminA-Content.pdf) and by food name (https://ods.od.nih.gov/pubs/usdandb/VitaminA-Food.pdf) and foods containing beta-carotene in mcg arranged by nutrient content (https://ods.od.nih.gov/pubs/usdandb/VitA-betaCarotene-Content.pdf) and by food name (https://ods.od.nih.gov/pubs/usdandb/VitA-betaCarotene-Food.pdf).

Table 2 suggests many dietary sources of vitamin A. The foods from animal sources in Table 2 contain primarily preformed vitamin A, the plant-based foods have provitamin A, and the foods with a mixture of ingredients from animals and plants contain both preformed vitamin A and provitamin A.

Table 2. Selected Food Sources of Vitamin A

Food	mcg RAE per serving	IU per serving	Percent DV*
Sweet potato, baked in skin, 1 whole	1,403	28,058	561
Beef liver, pan fried, 3 ounces	6,582	22,175	444
Spinach, frozen, boiled, ½ cup	573	11,458	229
Carrots, raw, ½ cup	459	9,189	184
Pumpkin pie, commercially prepared, 1 piece	488	3,743	249
Cantaloupe, raw, ½ cup	135	2,706	54
Peppers, sweet, red, raw, ½ cup	117	2,332	47
Mangos, raw, 1 whole	112	2,240	45
Black-eyed peas (cowpeas), boiled, 1 cup	66	1,305	26
Apricots, dried, sulfured, 10 halves	63	1,261	25
Broccoli, boiled, ½ cup	60	1,208	24
Ice cream, French vanilla, soft serve, 1 cup	278	1,014	20
Cheese, ricotta, part skim, 1 cup	263	945	19
Tomato juice, canned, ¾ cup	42	821	16
Herring, Atlantic, pickled, 3 ounces	219	731	15
Ready-to-eat cereal, fortified with 10% of the DV for vitamin A, ¾–1 cup (more heavily fortified cereals might provide more of the DV)	127–149	500	10
Milk, fat-free or skim, with added vitamin A and vitamin D, 1 cup	149	500	10
Baked beans, canned, plain or vegetarian, 1 cup	13	274	5
Egg, hard boiled, 1 large	75	260	5
Summer squash, all varieties, boiled, ½ cup	10	191	4
Salmon, sockeye, cooked, 3 ounces	59	176	4
Yogurt, plain, low fat, 1 cup	32	116	2
Pistachio nuts, dry roasted, 1 ounce	4	73	1
Tuna, light, canned in oil, drained solids, 3 ounces	20	65	1
Chicken, breast meat and skin, roasted, ½ breast	5	18	0

Footnote: *DV = Daily Value. FDA developed DVs to help consumers compare the nutrient contents of products within the context of a total diet. The Daily Value (DV) for vitamin A used for the values in Table 2 is 5,000 IU for adults and children age 4 years and older ⁴. This Daily Value, however, is changing to 900 mcg RAE as the updated Nutrition and Supplement Facts labels are implemented ¹⁷; (1 mcg RAE = 1 mcg retinol, 2 mcg beta-carotene from supplements, 12 mcg beta-carotene from foods, 24 mcg alpha-carotene, or 24 mcg beta-cryptoxanthin). The updated labels and DVs must appear on food products and dietary supplements beginning in January 2020, but they can be used now ¹⁸. FDA requires current food labels to list vitamin A content, but this requirement will be dropped with the updated labels. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.

[Source ⁵ ]

Carotenemia prognosis

A low-carotene diet leads to progressive disappearance of the yellow skin discoloration. Because of the lipophilic nature of carotenoids, however, sufficient amounts can remain in tissue for several months, causing yellow skin even after serum carotene levels return to normal.

Carotenemia is a benign condition. Complications are rare with diet-induced carotenemia; Vitamin A poisoning does not occur even with massive doses of carotene, because the conversion of carotene to vitamin A takes place slowly. However, a man who had allegedly ingested 6-7 pounds of carrots per week was observed with constipation, hypercarotenemia, elevated liver enzyme levels, and possible vitamin A toxicity ¹⁹.

A correlation between metabolic carotenemia and biliary dyskinesia has been suggested. In patients with metabolic carotenemia, significant relationships were identified between the gall bladder contraction rate and the levels of serum carotene, vitamin A, and lipids.

Amenorrhea may be associated with carotenemia. This occurs in patients who consume a pure or predominantly vegetarian diet without red meat. Dietary modifications can reduce carotene levels, which, in turn, normalize the menstrual cycle.

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