Vitamin A

 Vitamin A

Introduction

It is an essential human nutrient. It is a fat soluble vitamin

Vitamin A is a generic term for a large number of related compounds(2)

It can be divided into two categories

Ø  Retinoids: in foods of animal origin, the major form of vitamin A is an alcohol (retinol), or as an acid (retinoic acid),they are called performed vitamin A, but can also exist as an aldehyde (retinal).

Ø  Carotenoids : Precursors to the vitamin (a provitamin) are present in foods of plant origin( colored fruits and vegetables ), some of the members of the carotenoid family are beta-carotene, alpha-carotene, and beta- cryptoxanthin .

Among these, beta-carotene is most efficiently made into retinol . Alpha-carotene and beta- cryptoxanthin are also converted to vitamin A, but only half as efficiently as beta-carotene.

The discovery of vitamin A stemmed from research dating back to 1906 and it was the first lipo-soluble vitamin to be recognized by Moray 1922.

Sources

The richest food are (liver "beef, pork, chicken” , eggs , butter Milk and its products ).

carrots ,  Broccoli  , sweet potatoes , kale spinach .

Leafy vegetables , pumpkin , mango , apricots and papaya .

Fortified foods( low-fat , skim milk ,  margarine and most ready-to-eat and instant prepared cereals  )are often fortified with vitamin A because it is lost during processing ,  so  it is important to check the label on the package for the vitamin A content to obtain the RDA

2. Supplements:

The principal forms of preformed vitamin A (retinol ) are retinyl palmitate and retinyl acetate .

Beta carotene are common source of vitamin A in supplements.

Both may be combined in supplements

Equivalencies of retinoids and carotenoids (IU)

Vitamin A intake is often expressed in international units (IU) or as retinol equivalents (RE), with 1 micrograms retinol = 3.3 IU =6 micrograms beta carotene.

Recommended daily intake

Vitamin A US Dietary Reference Intake:

900 micrograms (3000 IU) for men

700 micrograms (2300 IU) for women.

Upper limit 3,000 micrograms (10,000 IU).

Role in the body :

Promoting vision (retinol – retinal )

Regulation of gene expression (retinoic acid )

Immunity (retinal and retinoic acid )

Supporting reproduction and growth(retinal)

Red blood cells production

Beta-carotene as antioxidant (4)

Disease Treatment

Vitamin A status

Vitamin A status depends on:

Adequacy of vitamin A stores , 90% of which are in the liver.

A person's protein status because retinol binding proteins serve as the vitamin's transport carriers inside the body .(4)

Nutrient interactions

Zinc

Zinc deficiency is thought to interfere with vitamin A metabolism in several ways affecting  vitamin A nutritional status in humans

Iron

Vitamin A deficiency may exacerbate iron deficiency anemia. (Moreover, studies in rats have shown that iron deficiency alters plasma and liver levels of vitamin A)

Deficiency
 Children who are considered to be at increased risk for subclinical vitamin A deficiency include:

Preschool age children.

Children living at or below the poverty level.

Children with inadequate health care or immunizations.

Children living in areas with known nutritional deficiencies.

Children with diseases of the pancreas, liver, or intestines, or with inadequate fat digestion or absorption.

Manifestations of hypovitaminosis

Night blindness, corneal drying (xerosis), triangular gray spots on eye (Bitot's spots), corneal degeneration and blindness (xerophthalmia) , impaired immunity (Vitamin A deficiency can be considered a nutritionally acquired immunodeficiency disease) , hypokeratosis (white lumps at hair follicles), softening of the cornea (keratomalacia).

Children who are only mildly deficient in vitamin A have    a higher incidence of respiratory disease and diarrhea as well as a higher rate of mortality from infectious  diseases

Vitamin A deficiency in the opt :

22% of children were found to have low vitamin -A plasma levels (<200 μg/L) , Furthermore, more than half of the children participating in the study (53.9%) had levels of vitamin A in the range of 200-299 μg/L , meaning that 75.9% of children had vitamin A levels below 300 μg/L.

The results showed a significant difference between the prevalence of vitamin A deficiency in the West Bank (18.9 per cent) compared to the Gaza Strip (26.5 per cent), but no difference with respect to gender, age groups or refugee status.

Overdose and toxicity
( Hypervitaminosis )

As vitamin A is fat-soluble, disposing of any excesses leads to toxicity.

Children are more vulnerable to toxicity because they need less and are more sensitive to overdoses

vitamin A toxicity occurs when all binding proteins are swamped and free vitamin A damages the cells .

Acute toxicity generally occurs at doses of 25,000 IU/kg.This can lead to nausea, jaundice, irritability, anorexia vomiting, blurry vision, headaches, muscle and abdominal pain and weakness, drowsiness and altered mental status.

Chronic toxicity occurring at 4,000 IU/kg daily for 6-15 months.In chronic cases, hair loss, drying of the mucous membranes, fever, insomnia, fatigue, weight loss, bone fractures, anaemia, and diarrhoea (5)

Overdose and toxicity
( Hypervitaminosis )

Liver toxicities can occur at levels as low as 15,000 IU per day to 1.4 million IU per day, with an average daily toxic dose of 120,000 IU per day.

In people with renal failure 4000 IU can cause substantial damage.

Beta carotene from food is likely to cause this toxicity as it is not converted efficiently enough in the body to vitamin A , it is stored in the fat just under the skin and turn skin yellow . In contrast from supplement is harmful.

Excessive vitamin A over years weakens the bone and contribute to osteoporosis

Birth defects and Safety in pregnancy

Excessive vitamin A  has a teratogenic risk (10000 IU before 7th week of pregnancy).

Some current issues and controversies about vitamin A

Since 1987, WHO has advocated the routine administration of vitamin A with polio, multi-antigen and measles vaccine in countries where vitamin A deficiency is a problem, also supplementation to  postpartum mothers can improve the vitamin A content of their breast milk.(6)

Vitamin A, beta carotene, and cancer

Dietary intake studies suggest an association between diets rich in beta-carotene and vitamin A and a lower risk of many types of cancer

Fontham ETH. Protective dietary factors and lung cancer. Int J Epidemiol 1990;19:S32-S42. [PubMed abstract]

Vitamin A and osteoporosis limited experience data

Results of some studies indicate that long term intake of performed vitamin A of 1500 mcg /day ( not beta carotenes) increases risk of osteoporotic fracture by affecting mineral bone density .

Recommendation to obtain adequate vitamin A :

Vitamin A can be lost from foods during preparation, drying , or storage. To prevent loss of vitamin A:

Use raw fruits and vegetables whenever possible.

Keep vegetables (except sweet potatoes) and fruits covered and refrigerated during storage.

Steam vegetables and braise, broil meats instead of frying. Some of the vitamin A is lost in the fat during frying.

Food labeling to obtain RDA and avoid overdose .

Fortified foods and supplementations

Extra vitamin A to prevent deficiency

World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) recommend vitamin A administration for all children diagnosed with measles,” Measles may increase the body's utilization of vitamin A, possibly because of the rapid destruction of epithelial surfaces”,  in communities where vitamin A deficiency is a serious problem and where death from measles is greater than 1%.

Fat malabsorption can result in diarrhea and prevent normal absorption of vitamin A ( Celiac disease, Crohn's disease, and Pancreatic disorders)

Vegetarians: should choose dark green leafy vegetables and orange and yellow fruits to consume recommended amounts of vitamin A

 Give supplements to postpartum women and promoting breastfeeding is the best way to protect babies from VAD.

For deficient children: periodic supply of high-dose vitamin A is indicated .

Vitamin A supplementation reduces severe morbidity and mortality from infectious diseases among children .

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Homocysteine

 Homocysteine

Introduction

Homocystein is a homologue of the naturally-occurring amino acid cysteine

differing in that its side-chain contains an additional methylene (-CH2-) group before the thiol (-SH) group. 

Introduction

Alternatively, homocysteine can be derived from methionine by removing the latter's terminal Cε methyl group.

Homocysteine is not obtained from the diet; it is a normal temporary and chemically reactive reaction product that can be measured in blood!!

In blood, it is found bound to albumin and to hemoglobin.

It affects enzymes with cysteine-containing active sites, for example, it inhibits lysyl oxidase a key enzyme in the production of collagen and elastin, two main structural proteins in artery, bone and skin

Elevated homocysteine

Deficiencies of the vitamins folic acid (B9), pyridoxine (B6), or B12 (cyanocobalamin) can lead to high homocysteine levels.

Supplementation with pyridoxine, folic acid, B12 or trimethylglycine (betaine) reduces the concentration of homocysteine in the bloodstream.

Increased levels of homocysteine are linked to high concentrations of endothelial asymmetric dimethylarginine.

Elevations of homocysteine also occur in the rare hereditary disease homocystinuria and in the methylene-tetrahydrofolate-reductase polymorphism genetic traits.

Common levels in Western populations are 10 to 12 and levels of 20 μmol/L are found in populations with low B-vitamin intakes (New Delhi) or in the older elderly (Rotterdam, Framingham).

Women have 10-15% less homocysteine during their reproductive decades than men which may help explain the fact they suffer myocardial infarction (heart attacks) on average 10 to 15 years later than men.

How Much Is Safe?

Children with genetically elevated homocysteine levels experienced heart disease similar to the heart disease found in middle-aged patients.

People with elevated homocysteine levels are more likely to have strokes, Alzheimer's disease and dementia, kidney disease, diseases of the eye, erectile dysfunction, and, especially, heart disease.

Homocysteine and Heart Disease

Having an elevated homocysteine level is an independent risk factor for heart disease.

A highly elevated homocysteine level was associated with a more than 3-fold increase in the risk of heart attack over a 5-year period.

It causes thickening of the intima, or inner wall of the arteries.

homocysteine has been shown to affect the production of nitric oxide, a substance that causes arteries to relax and blood flow to increase.

Having an elevated homocysteine level has been associated with:

–        First and second heart attacks .

–        Coronary artery disease.

–        Total cardiovascular mortality.

–        Adverse outcomes after coronary balloon angioplasty.

–        Heart failure.

 Homocysteine Levels

Normal—5 to 15 µmol/L

Moderate—16 to 30 µmol/L

Intermediate—31 to 100 µmol/L

Severe—Above 100 µmol/L

People try to keep their homocysteine level between 7 µmol/L and 8 µmol/L.

A homocysteine level over 12 µmol/L should be treated aggressively.

One study found that each 3-µmol/L increase in homocysteine caused a significant increase in the risk of having a heart attack.

Homocysteine: Linked to Diseases of Aging

elevated homocysteine levels have been linked to the following disorders or diseases:

–        Stroke—Homocysteine's effect on the arteries that supply the brain with blood (carotid arteries) is similar to its effect on the arteries in the heart.

–        Vascular disease—There is evidence that homocysteine combines with low-density lipoprotein (LDL) cholesterol and contributes to the creation of plaque inside artery walls.

–        Homocysteine has also been implicated in the formation of blood clots, which can cause a heart attack, stroke, or peripheral vascular disease.

Liver disease—Elevated homocysteine and low levels of SAMe are linked to liver toxicity and cirrhosis. Homocysteine likely contributes to liver damage, leading to the formation of fibrin, clots, and vascular complications.

Kidney disease—The kidneys filter, reabsorb, and metabolize amino acids, including homocysteine. In kidney failure, homocysteine levels rise due to improper kidney filtration.

–        Folic acid, trimethylglycine, and vitamins B6 and B12 reduce homocysteine in people with kidney failure.

–        High doses of folic acid can normalize homocysteine levels. Once kidney failure occurs, folic acid is much less effective, and high doses of vitamin B12 are required to help normalize homocysteine levels

Thyroid conditions—Elevated homocysteine levels may contribute to accelerated heart disease among people who have hypothyroidism.

Alzheimer’s disease and dementia—High levels of homocysteine indicate impaired methylation in the brain. Individuals with Alzheimer's disease have been shown to have elevated homocysteine levels.

Depression—Depression has been linked to low levels of folic acid in women. Low folic acid levels have been shown to decrease the effectiveness of the antidepressant fluoxetine (Prozac®), and vitamin B6 may alleviate depression.

Erectile dysfunction—Homocysteine has been shown to reduce the production of nitric oxide. Nitric oxide causes blood vessels to relax, increasing blood flow to organs and tissues. In one case study, a man with erectile dysfunction, who also had a genetic defect that causes elevated homocysteine levels, did not initially respond to treatment with sildenafil (Viagra®). However, after treatment with 5000 micrograms (mcg) of folic acid and 1000 mcg of vitamin B12, his erectile dysfunction was successfully treated with sildenafil.

Diseases of the eye

                Homocysteine's ability to damage blood vessels also has implications for the tiny blood vessels in the eye. Elevated homocysteine levels are associated with serious eye conditions, including glaucoma and macular degeneration. A study showed that homocysteine levels of 11.6 µmol/L were the average concentrations in patients who had central retinal vein occlusion.

Why Homocysteine Levels Rise?

–        They rise naturally as we age.

–        Genes also play a large role in the body's metabolism of homocysteine.

–        Coffee and alcohol consumption increase homocysteine levels.

–        Eating foods that contain large amounts of methionine, such as red meat and chicken, increase blood levels of homocysteine.

–        low intake of foods rich in vitamin B, such as green leafy vegetables, may also increase homocysteine levels.

In addition, the following pharmaceuticals are associated with elevated homocysteine levels:

–        Fenofibrate—Used in the treatment of high cholesterol.

–        Niacin—Used in the treatment of lipid management.

–        Metformin—Used to treat diabetes.

–        Antiepileptic drugs—Used to control seizures.

–        Levodopa—Used to manage Parkinson's disease.

–        Methotrexate—Used to treat cancer, psoriasis, arthritis, and lupus.

. The Life Extension Foundation's approach to lowering homocysteine relies on several principles:

–        Directly addressing high homocysteine levels by increasing metabolization of homocysteine. Nutrients that increase metabolization of homocysteine fall into two categories:

•          those that increase the remethylation of homocysteine back into SAMe, and

•          those that act along the transsulfuration pathway to remove excess homocysteine from the body.

Routine blood testing to monitor homocysteine levels. This should include genetic testing to check for abnormalities. Slight genetic defects in as few as two enzymes may cause moderate hyperhomocysteinemia. the most serious form of hyperhomocysteinemia (homocystinuria) is caused by an extremely rare genetic disorder.

Addressing the damage directly caused by homocysteine. This may mean supplementing with antioxidants and other nutrients to reduce damage caused by homocysteine.

Managing underlying conditions—including high blood pressure, coronary artery disease, diabetes, and hypothyroidism—that are associated with a high homocysteine level.

The B Vitamins: A Powerful Weapon:

               

                _{Management of hyperhomocysteinemia begins with folic acid, vitamin B6, and vitamin B12. To varying degrees, folic acid and vitamin B12 increase the remethylation of homocysteine back into SAMe. Vitamin B6 is necessary for the conversion of homocysteine into glutathione along the transsulfuration pathway.}

TMG and Zinc: Bringing Homocysteine Under Control:

–        TMG (trimethylglycine) and zinc, both of which enhance the action of B vitamins.

–        TMG operates along a different pathway than the B vitamins. its activity is limited to the liver and kidneys.

–        Zinc acts in concert with vitamin B6 to promote remethylation of homocysteine to methionine.

–        Zinc is also needed for the conversion of homocysteine to cysteine and glutathione.

Inhibiting the Formation of Homocysteine:

Not all the homocysteine created is released directly into the bloodstream as free homocysteine. In fact, less than 1 percent of the homocysteine in the blood is free. The majority, about 98 to 99 percent, is bound to proteins in the blood and considered stored.

This store of homocysteine may be released in response to decreased methylation or oxidative damage, or in response to other influences.

Nutrients that have been shown to inhibit the release of homocysteine include:

–        Creatine—Somewhere between 50 and 90 percent of the SAMe required by the body goes into the production of creatine. Supplementation with creatine diminishes the need for SAMe, reduces formation of homocysteine, and the need for homocysteine remethylation.

–        Choline-producing nutrients—SAMe is involved in the production of choline. By taking choline-producing nutrients, your body produces less SAMe, which reduces the amount of homocysteine needed. Choline-producing nutrients include cytidine diphosphate (CDP) choline, lecithin, alpha-glycerylphosphorylcholine, and choline chloride.

Recommendations

It is important to begin your homocysteine-lowering program by working with a qualified physician and taking the necessary blood tests to evaluate your risk. To help lower your homocysteine level, the Life Extension Foundation suggests:

–        Folic acid—4000 to 8000 mcg daily

–        Vitamin B12—1 to 2 mg daily

–        Vitamin B6—100 to 200 mg daily

–        SAMe—400 mg two to four times daily

–        TMG—2 to 4 grams daily

–        Zinc—30 to 90 mg daily

–        CDP choline—250 to 500 mg daily

–        Micronized creatine—500 mg (in capsule form) four to eight times daily

–        N-acetyl-cysteine—600 mg (in capsule form) one to two times daily on an empty stomach

THANKS

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